Health Benefits of Aspirin

Aspirin use = lower risk of death from chronic liver disease

Aspirin use is associated with a decreased risk of developing hepatocellular carcinoma and death from chronic liver disease (CLD), according to a study published November 28, 2012 in the Journal of the National Cancer Institute.

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, occurs mainly among patients with CLD. Previous reports have linked chronic inflammation due to CLD to cellular processes that could promote carcinogenesis. Because of their anti-inflammatory properties and widespread use to prevent cardiovascular and cerebrovascular disease, nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and nonaspirin NSAIDs are being investigated as cancer chemopreventive agents. NSAIDs have been shown to have a beneficial effect in observational studies and clinical trials on risk of some cancers. However, the relationship between NSAID use and risk of HCC and death from CLD is unclear.

To investigate this relationship, Vikrant V. Sahasrabuddhe, M.B.B.S., Dr.P.H, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and colleagues, performed an observational study of 300,504 men and women aged 50 to 71 years enrolled in the National Institutes of Health-AARP Diet and Health Study who reported their aspirin and nonaspirin NSAID use and were followed-up for 10-12 years. The researchers linked the self-reported use of aspirin and nonaspirin NSAIDs to registry data on diagnoses of 250 cases of HCC and 428 deaths due to CLD to perform their study.

The researchers found that the use of NSAIDs was associated with a reduced risk of HCC and a reduced risk of death from CLD compared to non-users. Study participants who used aspirin had a 41% reduced risk of HCC and a 45% reduced risk of death from CLD, whereas those who used non-aspirin NSAIDs experienced a 26% reduced risk of CLD mortality but no reduced risk of HCC. The authors conclude that "these associations are prominent with the use of aspirin, and if confirmed, might open new vistas for chemoprevention of HCC and CLD."

In an accompanying editorial, Isra G. Levy, M.B., BCh., MSc., and Carolyn P. Pim, M.D., both from the Department of Epidemiology and Community Medicine at the University of Ottawa in Canada discuss how the known causes of chronic liver disease and primary liver cancer are hepatitis B and C virus infections, alcohol use, and a link between obesity and diabetes has been suggested. "We already have cheap, readily available interventions," such as vaccines for hepatitis B and C virus but "effective strategies for reduction of HBV and HCV are not always available or fully applied." Also, alcohol abuse and obesity are complex and multifactorial challenges that require interventions at the individual and system levels." They conclude that although we should study the potential of new chemopreventive strategies such as NSAID use, we should also continue to focus on improving the established practices and interventions.

Aspirin blocks tumor growth in some colorectal cancer

Aspirin has the potential to block tumor growth in certain patients with colorectal cancer, according to an editorial in the Oct. 25, 2012 issue of the New England Journal of Medicine by a University of Alabama at Birmingham oncologist. In a study that appears in the same issue, researchers examined the use of aspirin in the treatment outcomes of patients with colorectal cancer.

Researchers collected experimental data from 964 patients with colorectal cancer, separating them into two groups based on the presence or absence of a mutation within the PIK3CA gene. The authors found that the use of aspirin after diagnosis in patients with the gene mutation was associated with a 46 percent reduction in overall mortality and an 82 percent reduction in colorectal cancer-specific mortality. In contrast, aspirin use in patients without the mutation did not affect either overall or colorectal-specific mortality.

“Approximately 17 percent of patients with colorectal cancer have a tumor that carries a mutated PIK3CA gene,” says Boris Pasche, M.D., Ph.D., director of the UAB Division of Hematology and Oncology. “Hence, more than one in every six patients with locally advanced colorectal cancer may benefit from this therapy.”

Every year, more than 140,000 Americans are diagnosed with colorectal cancer, and more than 50,000 people die from the disease. Colorectal cancer is the third most common cause of death from cancer in the United States and the fourth worldwide.

Over the past decade, little progress has been made in the treatment of locally advanced colorectal cancer, which is defined as cancer that has spread to nearby tissue or lymph nodes but has not metastasized, or spread to other organs. “While several new drugs have proven useful in the treatment of metastatic colorectal cancer, only one of them has demonstrated efficacy in locally advanced colorectal cancer,” Pasche says.

Pasche notes that the sample size for the current study was small. Only 66 patients with the PIK3CA mutation used aspirin after being diagnosed with colorectal cancer and only three of them died of colorectal cancer during the follow-up. “Although we are intrigued about these findings, they are still preliminary, and larger prospective studies need to be conducted,” says Pasche.

One cause of concern is that aspirin is known to increase the risk of gastrointestinal bleeding and hemorrhagic strokes, Pasche notes. Although many Americans use baby aspirin daily to reduce their risk of heart disease, patients are generally only advised to do so when their cardiac risk is presumed to outweigh the risk of taking aspirin.

“We haven’t reached the point where we can make a big leap and advise patients to take aspirin to prevent cancer recurrence after surgery, but we are accumulating more information that helps us understand the role that aspirin can potentially play in cancer,” says Pasche. “As it is with any type of cancer treatment, we need to examine the benefits against the risks, but aspirin may well become one of the oldest drugs to be used as a 21st-century targeted therapy.

Aspirin may decrease risk of aggressive form of ovarian cancer

New research shows that women who regularly use pain relief medications, particularly aspirin, have a decreased risk of serous ovarian cancer—an aggressive carcinoma affecting the surface of the ovary. The study published (October, 2012) in Acta Obstetricia et Gynecologica Scandinavica, a journal of the Nordic Federation of Societies of Obstetrics and Gynecology, reports that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), or other analgesics did not decrease ovarian cancer risk.

Ovarian cancer is the deadliest gynecological malignancy and the fifth-leading cause of death by cancer for women in developed countries. Previous studies report that Denmark has one of the highest incidence and mortality rates at 11 and 7 per 100,000 women, respectively. According to the Centers for Disease Control and Prevention (CDC), each year 20,000 women in the U.S. are diagnosed with ovarian cancer, with 90% of cases occurring in women older than 40 years of age and the greatest number in those 60 years or older.

"Ovarian cancer has a high mortality. Understanding what factors are involved in the development of this disease and investigating preventative interventions for women are vitally important," said lead author Dr. Susanne Kjær with the Danish Cancer Society Research Center. "Our study examined the role of analgesics in development of ovarian cancer."

For the present study, researchers used data from the malignant ovarian cancer (MALOVA) study, a population-based, case-control study investigating this cancer in Danish women between 1995 and 1999. The team analyzed data from 756 women with epithelial ovarian cancer, classified by type of glandular tumors (adenocarcinomas); 447 were serous, 138 were mucinous, and 171 were other types. A random sample of 1564 women between the ages of 35 and 79 were drawn from the general population as controls. Personal interviews were conducted to determine analgesic drug use.

Findings indicate that women taking aspirin on a regular basis decreased their risk of serous ovarian cancer (odds ratio, OR=.60). Researchers did not find a decrease in ovarian cancer risk in women who regularly used non-aspirin NSAIDs, acetaminophen, or other types of pain relievers.

Dr. Kjær concludes, "Our findings suggest a potential protective effect of analgesic use on ovarian cancer risk, but that benefit should be balanced against adverse effects of pain medication use, such as risk of bleeding and peptic ulcers." The authors recommend that larger studies, which accurately assess dosage, frequency and duration of pain medications, are necessary to understand the impact of analgesic use on ovarian cancer.

In his editorial, also published in this month's issue, Dr. Magnus Westgren from Karolinska University Hospital in Stockholm, Sweden concurs with the study authors that strategies for preventing ovarian cancer are imperative. Dr. Westgren discusses preventive procedures such as bilateral salingectomy (BSE)—a removal of the fallopian tubes—in women at risk for ovarian cancer.

"If we informed women about the possibility of performing BSE at repeat cesarean section for ovarian cancer prevention, it is likely that many women would opt for this procedure," writes Dr. Westgren. He suggests that gynecology professionals discuss changing policies and setting up randomized trials to further understand how BSE could reduce ovarian cancer risk.

Aspirin May Slow Brain Decline

Low dose aspirin may ward off cognitive decline in elderly women with a high risk of cardiovascular diseases such as heart disease and stroke, conclude researchers from the University of Gothenburg in Sweden who write about their five-year study in a paper published 3 October, 2012 in the online journal BMJ Open.

In their introduction, corresponding author Anne Börjesson-Hanson and colleagues explain that many studies have looked at the effect of non-steroidal anti- inflammatory drugs (NSAID) on cognitive decline and dementia, but few have looked at the effect of aspirin on these conditions.

Yet, while researchers have proposed that inflammation might be important in the development of cognitive decline and cardiovascular diseases, and low dose aspirin is widely prescribed to prevent cardiovascular disease, no study has yet examined the effect of aspirin on cognitive function in people at high cardiovascular risk.

For their study, the researchers followed 681 women aged between 70 and 92 for five years. 129 of the women were already taking aspirin at daily doses ranging from 75 and 160 mg, and after undergoing baseline assessments, 601 were classed as having high cardiovascular risk.

Over the study period, the participants underwent more tests of cognitive and thinking skills, including one commonly used in the UK to diagnose dementia, the Mini Mental State Examination (MMSE).

The results showed that while the MMSE scores for the overall group fell over the five years of the study, it fell less for those women taking aspirin.

But although other tests of memory and thinking showed a similar pattern, those results were not statistically significant.

By the end of the study, 41 of the participants developed dementia, but the rate was no different between those on aspirin and those who weren't.

In discussing the possible limitations of their study, the authors say they can't rule out that people with incipient cognitive decline might be less likely to take aspirin anyway.

They conclude that low-dose aspirin treatment "may have a neuroprotective effect in elderly women at high cardiovascular risk".

Simon Ridley, Head of Research at Alzheimer's Research UK, says in a press release:

"The results provide interesting insight into the importance of cardiovascular health on cognition, but we would urge people not to self-medicate with aspirin to try to stave off dementia."

He points out the study found no benefit from aspirin on overall dementia rates, and that previous trials investigating potential benefits of drugs like aspirin for dementia have been negative.

"We know that keeping our heart healthy through regular exercise, a healthy diet, not smoking and keeping our blood pressure and cholesterol in check, can help to reduce the risk of dementia," says Ridley, adding that research into risk factors for cognitive decline must nevertheless become a top priority in the UK because of its increasingly aging population.


Aspirin use and the risk of prostate cancer mortality
Experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, but clinical data have been limited. We investigated whether use of ACs was associated with the risk of death from prostate cancer.

This study, published online Aug. 27, 2012 in the Journal of Clinical Oncology., comprised 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor database with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP) or radiotherapy (RT). Of them, 2,175 (37%) were receiving ACs (warfarin, clopidogrel, enoxaparin, and/or aspirin). The risk of prostate cancer-specific mortality (PCSM) was compared between the AC and non-AC groups.

AC therapy, particularly aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The association was most prominent in patients with high-risk disease.

Study: daily aspirin linked to lower cancer mortality

A large new observational study finds more evidence of an association between daily aspirin use and modestly lower cancer mortality, but suggests any reduction may be smaller than that observed in a recent analysis. The study, appearing early online in the Journal of the National Cancer Institute (JNCI), (August, 2012) provides additional support for a potential benefit of daily aspirin use for cancer mortality, but the authors say important questions remain about the size of the potential benefit.

A recent analysis pooling results from existing randomized trials of daily aspirin for prevention of vascular events found an estimated 37% reduction in cancer mortality among those using aspirin for five years or more. But uncertainty remains about how much daily aspirin use may lower cancer mortality, as the size of this pooled analysis was limited and two very large randomized trials of aspirin taken every other day found no effect on overall cancer mortality.

For the current study, American Cancer Society researchers led by Eric J. Jacobs, Ph.D., analyzed information from 100,139 predominantly elderly participants in the Cancer Prevention Study II Nutrition Cohort who reported aspirin use on questionnaires, did not have cancer at the start of the study, and were followed for up to 11 years. They found daily aspirin use was associated with an estimated 16% lower overall risk of cancer mortality, both among people who reported taking aspirin daily for at least five years and among those who reported shorter term daily use. The lower overall cancer mortality was driven by about 40% lower mortality from cancers of the gastrointestinal tract (such as esophageal, stomach, and colorectal cancer) and about 12% lower mortality from cancers outside the gastrointestinal tract.

The reduction in cancer mortality observed in the current study is considerably smaller than the 37% reduction reported in the recent pooled analysis of randomized trials. The authors note that their study was observational, not randomized, and therefore could have underestimated or overestimated potential effects on cancer mortality if participants who took aspirin daily had different underlying risk factors for fatal cancer than those who did not. However, the study's large size is a strength in determining how much daily aspirin use might lower cancer mortality.

"Expert committees that develop clinical guidelines will consider the totality of evidence about aspirin's risks and benefits when guidelines for aspirin use are next updated," said Dr. Jacobs. "Although recent evidence about aspirin use and cancer is encouraging, it is still premature to recommend people start taking aspirin specifically to prevent cancer. Even low-dose aspirin can substantially increase the risk of serious gastrointestinal bleeding. Decisions about aspirin use should be made by balancing the risks against the benefits in the context of each individual's medical history. Any decision about daily aspirin use should be made only in consultation with a health care professional."

Aspirin reduces risk of Barrett's esophagus & cancer

Aspirin use appears to reduce the risk of Barrett's esophagus (BE), the largest known risk factor for esophageal cancer, according to a new study (July, 2012) in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association.

"The protective effect of aspirin use appears robust because the analyses suggests a dose-response relationship in which high-dose aspirin was significantly associated with decreased Barrett's esophagus risk," said Chin Hur, MD, MPH, of the Massachusetts General Hospital Institute for Technology Assessment and lead author of this study. "It would not be advisable at this time for patients to start taking aspirin, particularly at higher doses, if preventing Barrett's esophagus is the only goal. However, if additional data confirms our findings and an individual at high risk for development of Barrett's esophagus and esophageal cancer also could derive additional benefits, most notably cardiovascular, aspirin could be a consideration."

Dr. Hur and his team of researchers analyzed characteristics of 434 BE patients for factors that might be used in screening and management. In addition to finding that those taking aspirin were 44 percent less likely to have BE, they also found that men were more than three times more likely to develop BE than women.

The incidence of esophageal cancer has been increasing at an alarming rate during the past few decades; current attempts at targeted screening for this type of cancer focus on identifying BE. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, have been associated with reduced esophageal cancer incidence. Although there have been many studies analyzing NSAID and aspirin chemoprevention for esophageal cancer or BE progression to this cancer, few have explored NSAIDs for BE prevention.

Aspirin before heart surgery reduces the risk of post-operative acute kidney failure

Aspirin taken for five days before a heart operation can halve the numbers of patients developing post-operative acute kidney failure, according to research presented at the European Anaesthesiology Congress in Paris June 10, 2012.

Professor Jianzhong Sun (MD, PhD), professor and attending anaesthesiologist at Jefferson Medical College, Thomas Jefferson University (Philadelphia, USA), told the meeting that in a study of 3,219 patients, pre-operative aspirin therapy was associated with a reduction in acute renal failure of about three in every 100 patients undergoing coronary artery bypass graft (CABG), valve surgery or both.

The patients were divided into two groups: those taking aspirin within five days before their operation (2,247 patients) and those not taking it (972 patients) [1]. Although the researchers had no record of the precise dose taken, doses of between 80-325mg per day is the normal dose for aspirin that is taken over a period of time.

After adjusting their results for various differing characteristics such as age, disease, and other medications, the researchers found that pre-operative aspirin was associated with a significant decrease in the incidence of post-operative kidney failure: acute renal failure occurred in 86 out of 2247 patients (3.8%) taking aspirin, and in 65 out of 972 patients (6.7%) not taking it [1]. This represented an approximate halving in the risk of acute renal failure.

Prof Sun said: "Thus, the results of this clinical study showed that pre-operative therapy with aspirin is associated with preventing about an extra three cases of acute renal failure per 100 patients undergoing CABG or/and valve surgery."

Acute renal failure or injury is a common post-operative complication and has a significant impact on the survival of patients undergoing heart surgery. "It significantly increases hospital stay, the incidence of other complications and mortality," said Prof Sun. "From previous reports, up to 30% of patients who undergo cardiac surgery develop acute renal failure. In our studies, about 16-40% of cardiac surgery patients developed it in various degrees, depending upon how their kidneys were functioning before the operation. Despite intensive studies we don't understand yet why kidney failure can develop after cardiac surgery, but possible mechanisms could involve inflammatory and neurohormonal factors, reduced blood supply, reperfusion injury, kidney toxicity and/or their combinations."

He continued: "For many years, aspirin as an anti-platelet and anti-inflammatory agent has been one of the major medicines in prevention and treatment of cardiovascular disease in non-surgical settings. Now its applications have spread to surgical fields, including cardiac surgery, and further, to non-cardiovascular diseases, such as the prevention of cancer. Looking back and ahead, I believe we can say that aspirin is really a wonder drug, and its wide applications and multiple benefits are truly beyond what we could expect and certainly worthy of further studies both in bench and bedside research."

Prof Sun said that more observational and randomised controlled clinical trials were required to investigate the role played by aspirin in preventing post-operative kidney failure, but he believed that the effect might also be seen in patients undergoing non-cardiac surgeries.

"For instance, the PeriOperative ISchemic Evaluation-2 trial (POISE-2) [2] is ongoing and aims to test whether small doses of aspirin, given individually for a short period before and after major non-cardiac surgeries, could prevent major cardiovascular complications such as heart attacks and death, around the time of surgery."

Other findings from Prof Sun's research showed that diabetes, high blood pressure, heart disease, heart failure, and diseases of the vascular system were all independent risk factors for post-operative acute kidney failure.

Aspirin May Guard Against Skin Cancer

Aspirin and other commonly used painkillers may help guard against skin cancer, according to a new study about to be published online in the journal CANCER, that was led by researchers from Aarhus University Hospital in Denmark.

Previous studies have already suggested that NSAIDs (nonsteroidal anti-inflammatory drugs) such as aspirin, ibuprofen, and naproxen, and other prescription and over the counter drugs, can reduce people's risk of developing some cancers.

For example, earlier this year, three studies in The Lancet bolstered the evidence that a daily low dose of aspirin may protect people in middle age against cancer, particularly those at higher risk.

And in another recent study in the British Journal of Cancer, researchers from Leiden University Medical Centre in the Netherlands reported that colon cancer patients who take aspirin regularly shortly after diagnosis tend to live for longer.

In this latest study, Sigrún Alba Jóhannesdóttir and colleagues looked at the effect of these drugs on three major types of skin cancer: basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.

From medical records covering 1991 to 2009 of people living in northern Denmark, they found diagnoses of 1,974 cases of squamous cell carcinoma, 13,316 of basal cell carcinoma, and 3,242 of malignant melanoma.

The records also had information about prescription drugs, enabling the researchers to compare their use in the people with skin cancer to that of 178,655 people without a skin cancer diagnosis.

The results showed that:

* People with more than 2 prescriptions for NSAIDs has a 15% lower risk for squamous cell carcinoma and a 13% lower risk for malignant melanoma than those with fewer than 2 prescriptions.

* The link was even stronger when the drugs appeared to have been taken for 7 years or more, at a high intensity.

* Taking NSAIDs did not appear to be linked to a lower risk of developing basal cell carcinoma overall.

* But, taking NSAIDs was linked to a lower risk of developing this type of skin cancer in less exposed parts of the body (ie not the head or neck), particularly on a long term (15% reduced risk) or high intensity (21% reduced risk) basis.

Basal cell carcinoma is a type of nonmelanoma skin cancer that grows slowly and painlessly and rarely spreads. It is the most common form of cancer in the US. According to the American Cancer Society, 75% of all skin cancers are basal cell carcinomas. Squamous cell carcinoma is also a nonmelanoma type and grows a bit faster than basal cell carcinoma. Both of these types of nonmelanoma skin cancer are treatable.

Melanoma is the most dangerous type of skin cancer and can spread to other parts of the body very quickly. Some cases can be cured if caught very early. Melanoma is the leading cause of death from skin disease.

Colon Cancer Survival Improves With Aspirin

Colon cancer patients who take aspirin regularly shortly after diagnosis tend to live longer, researchers from Leiden University Medical Centre, the Netherlands, reported in the British Journal of Cancer. (April, 2012)

The authors explain that NSAIDs (non-steroid anti-inflammatory drugs) have been known to have a preventive role with regards to colorectal cancer, and in particular, aspirin. Recently, some studies and experts have suggested that regular aspirin may have a therapeutic role too. However, studies so far have not been conclusive.

Dr Gerrit-Jan Liefers and team set out to determine what the therapeutic effect of aspirin/NSAIDs as adjuvant treatment might be on colorectal cancer patients after diagnosis. They carried out an observational population-based study.

They gathered prescription data from the PHARMA linkage systems, focusing on patients who had been diagnosed with colorectal cancer (1998-2007). They selected people from the Eindhoven Cancer Registry, a population-based cancer registry.

Patients were classified into:

* Pre-diagnosis and post-diagnosis - aspirin/NSAID users

* Pre-diagnosis and post-diagnosis - non-aspirin/NSAID users

* Just post-diagnosis - aspirin/NSAID users

* Just post-diagnosis - non-aspirin/NSAID users

Out of 4,481 participants:

* 26% (1,1176) of them were non-aspirin/NSAID users

* 47% (2,086) of them were pre- and post-diagnosis aspirin/NSAID users

* 27% (1,219) of them were just post-diagnosis aspirin/NSAID users

Those taking a daily dose of aspirin for nine months or more after diagnosis had a 30% lower risk of cancer-related death compared to non-users. Even taking aspirin regularly for any length of time reduced the risk of death (by 23%).

Aspirin's potential role in reducing the risk of cancer death

A new report by American Cancer Society scientists says new data showing aspirin's potential role in reducing the risk of cancer death bring us considerably closer to the time when cancer prevention can be included in clinical guidelines for the use of aspirin in preventive care. The report, published early online in Nature Reviews Clinical Oncology (April, 2012), says even a 10% reduction in overall cancer incidence beginning during the first 10 years of treatment could tip the balance of benefits and risks favorably in average-risk populations.

Current guidelines for the use of aspirin in disease prevention consider only its cardiovascular benefits, weighed against the potential harm from aspirin-induced bleeding. While daily aspirin use has also been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, these benefits alone do not outweigh harms from aspirin-induced bleeding in average-risk populations. But recently published secondary analyses of cardiovascular trials have provided the first randomized evidence that daily aspirin use may also reduce the incidence of all cancers combined, even at low doses (75-100 mg daily).

The current review, led by Michael J. Thun, M.D., vice president emeritus of epidemiology and surveillance research for the American Cancer Society was not designed as a comprehensive review of the literature, but instead is a focused discussion of the key outstanding issues in using aspirin as a cancer prevention tool.

The report says recently published meta-analyses of results from randomized trials of daily aspirin treatment to prevent vascular events have provided provocative evidence that daily aspirin at doses of 75 mg and above might lower both overall cancer incidence and overall cancer mortality.

In six primary prevention trials of daily low-dose aspirin, randomization to aspirin treatment was associated with an approximately 20% reduction in overall cancer incidence between 3 and 5 years after initiation of the intervention (metaodds ratio [OR] = 0.81; 95% CI 0.67-0.98) and a 30% reduction during follow up more than 5 years after randomization (meta-OR = 0.70; 95% CI 0.56-0.88). Cancer mortality was also reduced during study follow up that happened more than 5 years after the start of aspirin use (meta-OR = 0.63; 95% CI 0.49-0.82) in analyses that included 34 trials of daily aspirin at various doses. Surprisingly, the size of the observed benefit did not increase with daily doses of aspirin above 75-100 mg. Notably, these meta-analyses excluded results from the Women's Health Study (WHS), a large 10-year-long trial of 100 mg of aspirin taken every other day, which reported no reduction in cancer incidence or mortality.

"The accumulating data from randomized clinical trials provide an exciting opportunity to reconsider the potential role of aspirin in cancer prevention," write the authors. They say several important questions remain unanswered, such as the exact magnitude of the overall cancer benefit and which individual cancer sites contribute to this benefit. "However, these new data bring us considerably closer to the time when cancer prevention can be integrated into the clinical guidelines for prophylactic treatment following regulatory review by the FDA and the European Medicines Agency."

Why Don't More Women Take a Daily Aspirin to Prevent Heart Disease?

Heart disease is the leading cause of death among women, and evidence-based national guidelines promote the use of daily aspirin for women at increased risk for cardiovascular disease. However, less than half of the women who could benefit from aspirin are taking it, according to an article in Journal of Women’s Health, a peer-reviewed publication from Mary Ann Liebert, Inc. The article is available free online at the Journal of Women’s Health website.

“Based on this survey, it is evident that the majority of women for whom aspirin is recommended for prevention of cardiovascular disease are not following national guidelines,” says Editor-in-Chief Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women’s Health and Executive Director of the Virginia Commonwealth University Institute for Women’s Health, Richmond, VA.

Among more than 200,000 women participating in a web-based survey to assess their risk for cardiovascular disease, only 41%-48% of women for whom aspirin is recommended reported that they took an aspirin daily, according to the study authors, Cathleen Rivera, MD and Texas-based colleagues from Scott and White Healthcare, Navigant Healthcare Consultants, and Texas A&M Health Science Center. The women were more likely to use aspirin if they had a family history of cardiovascular disease or had high cholesterol, as reported in the article “Underuse of Aspirin for Primary and Secondary Prevention of Cardiovascular Disease Events in Women.” The authors conclude that improved educational programs are needed to increase awareness of the benefits of aspirin use to prevent heart disease among women.

Aspirin: High or Low Dose? No significant difference.

Researchers report no significant difference in high versus low dose aspirin in preventing recurring cardiovascular events.

Each year, more than one million Americans suffer a heart attack and nearly all patients are prescribed a daily aspirin and an antiplatelet medication during recovery. However, the optimal aspirin dose has been unclear. Now, new research from Brigham and Women's Hospital (BWH) reports that there is no significant difference between high versus low dose aspirin in the prevention of recurring cardiovascular events in patients who suffer from acute coronary syndromes (ACS), which are characterized by symptoms related to obstruction in coronary arteries, which supply blood to the heart. These findings were presented at the American College of Cardiology Scientific Sessions on March 24, 2012.

"We observed no difference between patients taking a high dose versus a low of aspirin as it relates to cardiovascular death, heart attack, stroke or stent thrombosis," said Payal Kohli, MD,cardiology fellow at BWH and researcher in the TIMI Study Group, who is the lead author on this study. "Interestingly, we did find a dramatic difference in practice patterns of physicians in North America compared to those in the rest of the world," Kohli said. "North American physicians prescribed a high dose of aspirin for two-thirds of all their patients, while the exact reverse was true of the rest of the world. International physicians prescribed a low dose of aspirin to more than two-thirds of their patients." Dr. Stephen D. Wiviott, a cardiologist at BWH and researcher in the TIMI Study Group, is the senior author on the study.

Researchers analyzed data from more than 11000 patients from around the world that were enrolled in the TRITON-TIMI 38 trial, which randomized ACS patients to receive either clopidigrel or prasugrel, two different antiplatelet medications. Some patients were prescribed high doses of aspirin following a heart attack, while others, low doses. The aspirin dose was prescribed at the clinician investigator's discretion and the analysis included 7,106 patients who received low dose aspirin, defined as 150 mg or less, and 4,610 patients who received high dose aspirin, defined as 150 mg or more. Researchers reported that there was no significant difference observed in the prevention of the combination of heart attack, stroke, cardiovascular death or the prevention of stent thrombosis between the groups that received high or low dose aspirin.

Aspirin lowers trans fat-related stroke risk in older women

Older women whose diets include a substantial amount of trans fats are more likely than their counterparts to suffer an ischemic stroke, a new study shows.

However, the risk of stroke associated with trans fat intake was lower among women taking aspirin, according to the findings from University of North Carolina at Chapel Hill researchers.

The study, "Trans Fat Intake, Aspirin and Ischemic Stroke Among Postmenopausal Women," was published March 1, 2012 online in the journal Annals of Neurology.

The study of 87,025 generally healthy postmenopausal women aged 50 to 79 found that those whose diets contained the largest amounts of trans fats were 39 percent more likely to have an ischemic stroke (clots in vessels supplying blood to the brain) than women who ate the least amount of trans fat. The risk was even more pronounced among non-users of aspirin: those who ate the most trans fat were 66 percent more likely to have an ischemic stroke than females who ate the least trans fat.

However, among women who took aspirin over an extended period of time, researchers found no association between trans fat consumption and stroke risk – suggesting that regular aspirin use may counteract trans fat intake's adverse effect on stroke risk among women.

Trans fat is generally created in the food production process and is found in commercially prepared foods, including many shortenings, cake mixes, fried fast foods, commercially baked products (such as doughnuts, cakes and pies), chips, cookies and cereals.

Researchers from the UNC Gillings School of Global Public Health studied women who were enrolled in the Women's Health Initiative Observational Study. From 1994 to 2005, 1,049 new cases of ischemic stroke were documented.

Women who consumed the highest amount of trans fat also were more likely to be smokers, have diabetes, be physically inactive and have lower socioeconomic status than those who consumed the least trans fat, the study showed.

"Our findings were contrary to at least two other large studies of ischemic stroke," said Ka He, Sc.D., M.D., associate professor of nutrition and epidemiology at the UNC public health school. "However, ours was a larger study and included twice as many cases of ischemic stroke. Our unique study base of older women may have increased our ability to detect the association between trans fat intake and ischemic stroke among non-users of aspirin."

He said aspirin may lower the risk of ischemic stroke because of its anti-inflammatory and anti-platelet clumping properties.

The UNC researchers did not find any association between eating other kinds of fat (including saturated, monounsaturated or polyunsaturated fat) and ischemic strokes.

"Our findings highlight the importance of limiting the amount of dietary trans fat intake and using aspirin for primary ischemic stroke prevention among women, especially among postmenopausal women who have elevated risk of ischemic stroke," said lead author Sirin Yaemsiri, a doctoral student in the school's epidemiology department.

Regular aspirin intake halves cancer risk

Scientists have discovered that taking regular aspirin halves the risk of developing hereditary cancers.

Hereditary cancers are those which develop as a result of a gene fault inherited from a parent. Bowel and womb cancers are the most common forms of hereditary cancers. Fifty thousand people in the UK are diagnosed with bowel and womb cancers every year; 10 per cent of these cancers are thought to be hereditary.

The decade-long study, which involved scientists and clinicians from 43 centres in 16 countries and was funded by Cancer Research UK, followed nearly 1,000 patients, in some cases for over 10 years. The study found that those who had been taking a regular dose of aspirin had 50 per cent fewer incidences of hereditary cancer compared with those who were not taking aspirin. The research was published in the Lancet Online on Oct. 28 2011.

The research focused on people with Lynch syndrome which is an inherited genetic disorder that causes cancer by affecting genes responsible for detecting and repairing damage in the DNA. Around 50 per cent of those with Lynch syndrome develop cancer, mainly in the bowel and womb. The study looked at all cancers related to the syndrome, and found that almost 30 per cent of the patients not taking aspirin had developed a cancer compared to around 15 per cent of those taking the aspirin.

Those who had taken aspirin still developed the same number of polyps, which are thought to be precursors of cancer, as those who did not take aspirin but they did not go on to develop cancer. It suggests that aspirin could possibly be causing these cells to destruct before they turn cancerous.

Over 1,000 people were diagnosed with bowel cancer in Northern Ireland last year; 400 of these died from the disease. Ten per cent of bowel cancer cases are hereditary and by taking aspirin regularly the number of those dying from the hereditary form of the disease could be halved.

Professor Patrick Morrison from Queen's University in Belfast, who led the Northern Ireland part of the study, said: "The results of this study, which has been ongoing for over a decade, proves that the regular intake of aspirin over a prolonged period halves the risk of developing hereditary cancers. The effects of aspirin in the first five years of the study were not clear but in those who took aspirin for between five and ten years the results were very clear."

"This is a huge breakthrough in terms of cancer prevention. For those who have a history of hereditary cancers in their family, like bowel and womb cancers, this will be welcome news. Not only does it show we can reduce cancer rates and ultimately deaths, it opens up other avenues for further cancer prevention research. We aim now to go forward with another trial to assess the most effective dosage of aspirin for hereditary cancer prevention and to look at the use of aspirin in the general population as a way of reducing the risk of bowel cancer.

"For anyone considering taking aspirin I would recommend discussing this with your GP first as aspirin is known to bring with it a risk of stomach complaints, including ulcers."

Higher daily dose of aspirin prevents heart attacks

In some cases, an apple a day may keep the doctor away, but for people with diabetes, regular, over-the-counter aspirin may also do the job.

A new study by University of Alberta researcher Scot Simpson has shed light on the use of Aspirin as a preventive measure for cardiovascular disease and reoccurrence in patients with diabetes.

The study collected data from clinical trials that looked at whether taking aspirin as a course of treatment would prevent a first or recurrent heart attack or stroke.

Using information from diabetic patients in these studies, Simpson discovered that patients with previous cardiac episodes who were taking a low dose of aspirin daily had very little benefit in terms of prevention of a second heart attack or a decreased risk of mortality. However, in patients taking higher doses of aspirin, the risk of a repeat heart attack and/or death was significantly lower.

"We took all of the data from 21 studies and focused specifically on diabetic patients who had suffered a previous heart attack or stroke to measure the ability of aspirin to prevent a second event. We found that, if those patients took up to 325 milligrams of aspirin per day, they had a 23 percent lower risk of death," said Simpson.

Simpson, an associate professor in the Faculty of Pharmacy and Pharmaceutical Sciences, says that people with diabetes are at an increased risk of cardiovascular disease, adding there is evidence that suggests as much as 60 per cent of deaths in diabetics are attributable to heart disease. Simpson says he always suspected the aspirin dosage could play a role in treating cardiovascular disease in diabetics and felt because aspirin was an over-the-counter medication, it's something that pharmacists could have an active role in administering.

"The pharmacists' best role for chronic disease management is working proactively with physicians and patients," said Simpson. "Whether that means working directly with the physician, and consulting about prescribed medications, or when the patient is deciding about whether or not to take aspirin as part of a treatment plan, pharmacists can have a significant, positive impact."

Aspirin reduces the risk of cancer recurrence in prostate cancer patients

Some studies have shown that blood-thinning medications, such as aspirin, can reduce biochemical failure––cancer recurrence that is detected by a rising prostate-specific antigen (PSA) level––the risk of metastasis and even death in localized prostate cancer. These studies, although very telling, have all emphasized the need for more data. Now, with researchers at Fox Chase Cancer Center having concluded the largest study on this topic, and there is substantial data suggesting that aspirin improves outcomes in prostate cancer patients who have received radiotherapy.

A team led by Mark Buyyounouski, M.D., M.S., a radiation oncologist at Fox Chase, examined a database of over 2000 prostate cancer patients who underwent radiotherapy at Fox Chase between 1989 and 2006 and found that aspirin use lowers the risk of cancer recurrence. The scientists presented their findings on Sunday, May 1, 2011 at the 93rd Annual Meeting of the American Radium Society.

The team found that the 761 men who took aspirin at or after the time of radiotherapy were less likely to experience biochemical failure––as indicated by the levels of PSA––than were the 1380 men who didn't take the drug.

After 10-years from completion of treatment, 31% of the men who took aspirin developed recurrence compared with 39% of non-aspirin users (p=0.0005). There was also a 2% improvement in 10-year prostate cancer related survival associated with aspirin use with a trend toward statistical significance (p=0.07). "We know that prostate cancer has a long natural history and 15 years or more may be necessary to detect significant difference in survival," Dr. Buyyounouski explains. "Longer follow-up is needed, but these results warrant further study."

The readily available drug could be a promising supplement to radiotherapy in prostate cancer patients, and its beneficial effects may generalize to other types of cancer, Buyyounouski says. Still, he cautions that "it's a little premature to say that men need to start taking aspirin if they have a history of prostate cancer."

The optimal dose, timing, and duration of aspirin therapy, as well as potential side effects are not well understood, Buyyounouski explains. It's not clear how exactly the aspirin is helping and more research is needed to investigate this. "Its possible aspirin therapy is making the radiation more effective or preventing the cancer from spreading".

"Hopefully, these clinical results will provide feedback to laboratory researchers to try to explain the underlying mechanism so that we can better study the clinical effects in targeted populations," Buyyounouski says.

Aspirin may lower the risk of pancreatic cancer

The use of aspirin at least once per month is associated with a significant decrease in pancreatic cancer risk, according to results of a large case-control study presented at the AACR 102nd Annual Meeting 2011.

Xiang-Lin Tan, Ph.D., M.D., a research fellow at Mayo Clinic in Rochester, Minn., said the findings from this large collaborative study are preliminary and do not encourage widespread use of aspirin for this purpose.

"The results are not meant to suggest everyone should start taking aspirin once monthly to reduce their risk of pancreatic cancer," said Tan. "Individuals should discuss use of aspirin with their physicians because the drug carries some side effects."

For the current study, Tan and colleagues enrolled 904 patients who had documented pancreatic cancer and compared them with 1,224 healthy patients. All patients were at least 55 years old and reported their use of aspirin, NSAIDs and acetaminophen by questionnaire.

Results showed that people who took aspirin at least one day during a month had a 26 percent decreased risk of pancreatic cancer compared to those who did not take aspirin regularly. The effect was also found for those who took low-dose aspirin for heart disease prevention at 35 percent lower risk, according to Tan.

The researchers did not see a benefit from non-aspirin NSAIDs or acetaminophen. "This provides additional evidence that aspirin may have chemoprevention activity against pancreatic cancer," said Tan. He added that more data must be gathered before we can prove a real benefit.

Daily Aspirin at Low Doses Reduces Cancer Deaths

A daily low dose of aspirin significantly reduces the number of deaths from a whole range of common cancers, an Oxford University study has found.

The 20% drop in all cancer deaths seen in the study adds new evidence to the debate about whether otherwise healthy people in their 40s and 50s should consider taking a low dose of aspirin each day.

Aspirin is already known to be beneficial for those at high risk of heart disease. But among healthy people, the benefit in lower chances of heart problems only marginally outweighs the small risk of stomach bleeds.

The large size of the effect now seen in preventing cancer deaths may begin to tip the balance in favour of taking aspirin, the scientists suggest, but say that it is a matter for the health bodies who write treatment guidelines.

"These results do not mean that all adults should immediately start taking aspirin," cautions Professor Peter Rothwell of the Department of Clinical Neurology at Oxford University, who led the work. "But they do demonstrate major new benefits that have not previously been factored into guideline recommendations."

"Previous guidelines have rightly cautioned that in healthy middle aged people the small risk of bleeding on aspirin partly offsets the benefit from prevention of strokes and heart attacks, but the reductions in deaths due to several common cancers will now alter this balance for many people."

However, he adds: "I don't think it's necessarily right for the person who did the research to say what guidelines should be. We can't say with absolute certainty that there won't be some unknown harm in taking aspirin for 30 years, but it looks as if there would be pretty large benefits in reducing cancer deaths. People have to accept there's some uncertainty here."

Professor Rothwell and colleagues recently established that a low dose of aspirin (75 mg per day, or a quarter of the normal dose taken for pain relief) taken for longer than five years reduces death rates from bowel cancer by more than a third.

In this new work, scientists from Oxford, Edinburgh, London and Japan used data on over 670 deaths from cancer in a range of randomised trials involving over 25,000 people. These trials compared daily use of aspirin against no aspirin and were done originally to look for any preventative effect against heart disease.

The results, published in the Lancet, showed that aspirin reduced death due to any cancer by around 20% during the trials. But the benefits of aspirin only became apparent after taking the drug for 5 years or more, suggesting aspirin works by slowing or preventing the early stages of the disease so that the effect is only seen much later.

After 5 years of taking aspirin, the data from patients in the trials showed that death rates were 34% less for all cancers and as much as 54% less for gastrointestinal cancers, such as oesophagus, stomach, bowel, pancreas and liver cancers.

The researchers also wanted to determine if the benefits from aspirin continued over time. By using cancer registries and death records, they were able to follow up what had happened to participants in three of the trials.

They showed that risk of cancer death over a period of 20 years remained 20% lower for all solid cancers among those who had taken aspirin (even though they would have been unlikely to have continued taking aspirin after the trials finished), and 35% lower for gastrointestinal cancers.

It took about 5 years to see a benefit in taking aspirin for oesophagus, pancreatic, brain, and lung cancer; about 10 years for stomach and bowel cancer; and about 15 years for prostate cancer. The 20-year risk of death was reduced by about 10% for prostate cancer, 30% for lung cancer, 40% for bowel cancer and 60% for oesophagus cancer.

As the evidence points to a delayed preventative effect against cancer, Professor Rothwell believes that it would be those who started taking aspirin in their late 40s or 50s -- ie before people's risk of cancer starts increasing -- and then continued for 20 to 30 years who might eventually see the most benefit.

Professor Rothwell estimates that in terms of cost-effectiveness, taking low-dose aspirin daily is likely to be much more cost-effective than those interventions already used for preventing cancer, such as screening for breast or prostate cancer.

He does note that more research is necessary to understand more about the effect aspirin has on cancer.

While this study looked at how aspirin affected deaths from cancer, Professor Rothwell and colleagues now aim to look at any protective effect of aspirin on the incidence or progression of cancer. The researchers also point out that more trial data are needed on breast cancer and other cancers that particularly affect women.

"Perhaps the most important finding for the longer term is the proof of principle that cancers can be prevented by simple compounds like aspirin," says Professor Rothwell.

Low dose of aspirin wards off bowel cancer

Even the lowest possible dose of aspirin (75 mg) can ward off bowel cancer, if taken regularly, finds research published online in the journal Gut.

This protective effect is apparent after just one year and in the general population, not just those considered to be at risk of developing the disease, which is the second most common cause of cancer death in the world, killing almost half a million people every year.

Although previous research has shown that aspirin protects against bowel cancer, it is not known what the most effective dose is and how long it needs to be taken for.

The research team investigated just under 2,800 people with bowel cancer and just under 3,000 healthy people, matched for age, sex, and residential locality.

All participants completed food frequency and lifestyle questionnaires to assess their usual diet and lifestyle choices, which are known to influence bowel cancer risk.

NSAID (non-steroidal anti inflammatory drug) intake was categorised as taking more than four tablets a month of low dose aspirin (75 mg), other NSAIDs, or a mix.

The likelihood of surviving bowel cancer once diagnosed or developing the disease anew was then tracked over five years.

In all, 354 (15.5%) of those with bowel cancer were taking low dose aspirin compared with 526 (18%) of their healthy peers.

Taking any NSAID regularly, curbed the chances of developing bowel cancer compared with those who didn't take these painkillers.

This finding held true, irrespective of lifestyle choices, age, diet, weight, and level of deprivation

After a year, taking daily low dose aspirin was associated with a 22% reduced risk of developing bowel cancer, and the magnitude of the reduction in risk was cumulative, rising to 30% after five years.

Some 1,170 people died out of a total of 3,417 people diagnosed with bowel cancer (including those who were healthy at the start of the study) during the monitoring period. Most of these deaths (1,023) were attributable to the disease.

Information on NSAID intake was available for 676 of these 1,023 deaths, and it showed that taking NSAIDs of any kind did not influence the risk of death from any cause nor did it increase bowel cancer survival.

But, crucially, the findings show that high doses of aspirin, taken for a long time, are not needed to help ward off bowel cancer, say the authors.


The benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage

The American Heart Association:

“Background— Low-dose aspirin is an important therapeutic option in the secondary prevention of myocardial infarction (MI) and ischemic stroke, especially in light of its unique cost-effectiveness and widespread availability. In addition, based on the results of a number of large studies, aspirin is also widely used in the primary prevention of MI. This review provides an update of the available data to offer greater clarity regarding the risks of aspirin with respect to hemorrhagic stroke, as well as insights regarding patient selection to minimize the risk of this complication.

Summary of Review— In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage. The evidence from primary prevention of MI studies, including that from the recent Women’s Health Study evaluation of aspirin use in healthy women, demonstrate that the increased risk for hemorrhagic stroke is small, is comparable to the secondary prevention studies, and fails to achieve statistical significance. A reasonable estimate of the risk of hemorrhagic stroke associated with the use of aspirin in primary prevention patients is 0.2 events per 1000 patient-years, which is comparable to estimates of the risk associated with the use of aspirin in secondary prevention patients.

Conclusions— When considering whether aspirin is appropriate, the absolute therapeutic cardiovascular benefits of aspirin must be balanced with the possible risks associated with its use, with the most serious being hemorrhagic stroke.”

Another study (http://www.ynhh.org/healthlink/neurology/neurology_08_06.html ) had revealed that the 100 mg dose of aspirin every other day caused a 24 percent drop in the risk of ischemic stroke, which is the more common kind of stroke, and an insignificant increase in the risk of hemorrhagic stroke, hence the overall reduction in stroke risk of 17 percent.

Aspirin use lowers breast & ovarian cancer risk

Postmenopausal women who regularly use aspirin and other analgesics (known as painkillers) have lower estrogen levels, which could contribute to a decreased risk of breast or ovarian cancer.

"We observed some significant inverse associations between concentrations of several estrogens and the use of aspirin, aspirin plus non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and all analgesics combined," said Margaret A. Gates, Sc.D., research fellow at the Channing Laboratory at Brigham and Women's Hospital and Harvard Medical School.

"Our results suggest that among postmenopausal women, regular users of aspirin and other analgesics may have lower estrogen levels than non-users," Gates added.

These study results are published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Gates and colleagues examined the association between use of aspirin, NSAIDs and acetaminophen and concentrations of estrogens and androgens among 740 postmenopausal women who participated in the Nurses' Health Study.

Frequency of all analgesic use was inversely associated with estradiol, free estradiol, estrone sulfate and the ratio of estradiol to testosterone.

Average estradiol levels were 10.5 percent lower among women who regularly used aspirin or non-aspirin NSAIDs. Similarly, free estradiol levels were 10.6 percent lower and estrone sulfate levels were 11.1 percent lower among regular users of aspirin or other NSAIDs. Among regular users of any analgesic (aspirin, NSAIDs or acetaminophen), levels of these hormones were 15.2 percent, 12.9 percent and 12.6 percent lower, respectively, according to Gates.

Michael J. Thun, M.D., M.S., vice president emeritus of epidemiology and surveillance research at the American Cancer Society, said the question of whether regular use of aspirin and other NSAIDs is causally related to reduced breast cancer risk is important, but still unresolved.

Thun believes these study results do not confirm whether aspirin-like drugs caused the reduction in circulating estradiol. However, the results do provide evidence that aspirin and other NSAIDs might reduce circulating levels of estradiol by about 10 percent, according to Thun, who is an editorial board member of Cancer Epidemiology, Biomarkers & Prevention, and was not associated with this study.

"Hopefully these findings will motivate a trial to determine whether the association between aspirin use and hormone levels is causal," he said. "Until then, we have a possible mechanism for a potentially important, but as yet unproven chemopreventive benefit."

Gates agreed and said that additional research, like a randomized trial of NSAID use and hormone levels, is needed to confirm these results and to determine whether the decrease in hormone levels translates to a reduced risk of breast or ovarian cancer. If an inverse association between analgesic use and risk of breast or ovarian cancer is confirmed, then this research may have important public health implications.

"Although the overall risks and benefits would need to be weighed, analgesics could be implemented as a chemopreventive and may decrease the risk of several cancers," she said.

Breast Cancer Patients Who Take Aspirin Reduced Risk of Metastasis and Death by Half

An analysis of data from the Nurse’s Health Study, a large, ongoing prospective observational study, shows that women who have completed treatment for early-stage breast cancer and who take aspirin have a nearly 50 percent reduced risk of breast cancer death and a similar reduction in the risk of metastasis.

“This is the first study to find that aspirin can significantly reduce the risk of cancer spread and death for women who have been treated for early-stage breast cancer, " said Michelle Holmes, MD, DrPH, associate professor of medicine and epidemiology at Harvard Medical School & Harvard School of Public Health and the study's lead author. “If these findings are confirmed in other clinical trials, taking aspirin may become another simple, low-cost and relatively safe tool to help women with breast cancer live longer, healthier lives."

Investigators report it is not yet clear how aspirin affects cancer cells, but they speculate it decreases the risk of cancer metastasis by reducing inflammation, which is closely associated with cancer development. Prior studies have also suggested that aspirin inhibits cancer spread: one study found that people with colon cancer who took aspirin lived longer than those who did not, and laboratory studies have also shown that aspirin inhibited the growth and invasiveness of breast cancer cells.

In this analysis, researchers evaluated data from the Nurses' Health Study, which included 4,164 female nurses in the United States (ages 30 to 55 in 1976) who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002 and were followed through June 2006. They examined patients’ use of aspirin for one or more years after a breast cancer diagnosis (when patients would have completed treatment such as surgery, radiation therapy, and/or chemotherapy) and the frequency of metastasis and breast cancer death. (The authors emphasized that patients undergoing active treatment should not take aspirin due to potential interactions that can increase certain side effects.)

A total of 400 women experienced metastasis, and 341 of these died of breast cancer. Women who took aspirin two to five days per week had a 60 percent reduced risk of metastasis and a 71 percent lower risk of breast cancer death. Those who took aspirin six or seven days a week had a 43 percent reduced risk of metastasis and a 64 percent lower risk of breast cancer death. The risk of breast cancer metastasis and mortality did not differ between women who did not take aspirin and those who took aspirin once a week.

Researchers also found that women who took non-aspirin non-steroidal inflammatory drugs (NSAIDs) six or seven days a week also had a reduced risk of breast cancer death (a 48 percent reduction), but women who took NSAIDS less frequently and those who used acetaminophen did not experience such a benefit.

While the investigators did not collect data on aspirin dose, they noted that women who took aspirin regularly most likely took it for heart disease prevention; the typical dose for that purpose is 81 mg/day.

Benefit of Aspirin in Cardiovascular Disease

On November 15, 2009, Florida Atlantic University (FAU) researcher Charles H. Hennekens, M.D., presented at the American Heart Association's Annual Scientific Sessions meeting in Orlando, FL, the first data in humans to show that all doses of aspirin used in clinical practice increase nitric oxide. Nitric oxide is released from the blood vessel wall and may decrease the development and progression of plaques leading to heart attacks and strokes.

The abstract, titled "Usual Doses of Aspirin Increase Nitric Acid Formation in Humans" is published in the November 2009 issue of Circulation, the official journal of the American Heart Association.

FAU researchers conducted a randomized trial in patients at high risk of a first heart attack or stroke and assigned them to different doses of aspirin for 12 weeks. All doses produced highly significant beneficial effects on two important and well documented markers of nitric oxide formation.

"While the ability of aspirin to decrease the clumping of blood platelets is sufficient to explain why the drug decreases heart attacks and strokes, these data suggest a new and novel mechanism," said Hennekens.

Co-author and project director of the trial and affiliate clinical instructor of clinical science and medical education, Wendy Schneider, MSN, RN, said, "We are proposing new and longer term research to test whether this hypothesis has clinical or public health relevance."

The American Heart Association recommends aspirin use for patients who've had a myocardial infarction (heart attack), unstable angina, ischemic stroke (caused by blood clot) or transient ischemic attacks (TIAs or "little strokes"), if not contraindicated. This recommendation is based on sound evidence from clinical trials showing that aspirin helps prevent the recurrence of such events as heart attack, hospitalization for recurrent angina, second strokes, etc. (secondary prevention). Studies show aspirin also helps prevent these events from occurring in people at high risk (primary prevention).

Aspirin can reduce risk of Alzheimer's disease

Different types of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, and aspirin, appear to be equally effective in lowering the risk of Alzheimer’s disease, according to the largest study of its kind published in the May 28, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology. Experts have debated whether a certain group of NSAIDs that includes ibuprofen may be more beneficial than another group that includes naproxen and aspirin.

Using information from six different studies, researchers examined data on NSAID use in 13,499 people without dementia. Over the course of these six studies, 820 participants developed Alzheimer’s disease.

Researchers found that people who used NSAIDs had 23 percent lower risk of developing Alzheimer’s disease compared to those who never used NSAIDs. The risk reduction did not appear to depend upon the type of NSAID taken.

“This is an interesting finding because it seems to challenge a current theory that the NSAID group which includes ibuprofen may work better in reducing a person’s risk of Alzheimer’s,” said study author Peter P. Zandi, PhD, with Johns Hopkins Bloomberg School of Public Health in Baltimore, MD. “The NSAID group that includes ibuprofen was thought to target a certain type of plaque in the brain found in Alzheimer’s patients. But our results suggest there may be other reasons why these drugs may reduce the risk of Alzheimer’s.”

The study’s lead author Chris Szekely, PhD, with Cedars Sinai Medical Center in Los Angeles, says the discrepancy between studies such as this one and the negative clinical trials of NSAIDs in treatment or prevention of Alzheimer’s need to be further explored.

Aspirin at night = significant reductions in blood pressure

Data unveiled at the American Society of Hypertension's Twenty Third Annual Scientific Meeting and Exposition (ASH 2008) revealed for the first time that people with prehypertension who are treated with aspirin may experience significant reductions in blood pressure—but only if they take the pill before bedtime, and not when they wake up in the morning.

People with prehypertension (a blood pressure reading between normal and high; when systolic blood pressure is between 120 and 139 or diastolic blood pressure is between 80 and 89 on multiple readings) are at significant risk of hypertension, or consistently high blood pressure—the biggest risk factor for heart disease and stroke, the two leading causes of death in the Western world.

“This is the first study to reveal that taking aspirin before bedtime as opposed to upon waking in the morning is an effective strategy to lower blood pressure and cost effective way to individualize treatment regimes in pre-hypertensive patients," said lead investigator Prof. Ramón C. Hermida, Director of Bioengineering and Chronobiology at the University of Vigo in Spain. "These findings therefore have vital treatment implications for these at-risk patients throughout the world.”

The purposeful timing of medications in order to enhance beneficial outcomes or to avert adverse effects is known as ‘chronotherapeutics’. Although factors influencing why aspirin has an impact on prehypertensive patients in the evening and not the morning are somewhat unclear, researchers indicate that it could be because aspirin slows down the production of hormones and other substances in the body that cause clotting. Many of those are produced while the body is at rest.

The study, which ran for three months, involved 244 participants (97 men and 138 women of 43.0±13.0 years of age) all of whom had all received diagnoses for prehypertension. Participants were divided into three groups: non pharmacological hygienic-dietary recommendations (HDR): HDR and a 100mg tablet of aspirin (ASA) on awakening or HDR and ASA at bedtime. Blood pressure levels were monitored at 20 minute intervals from 7:00 a.m. to 11:00 p.m. and at 30-min intervals at night for 48 consecutive hours at baseline and after three months of intervention. Physical activity was simultaneously monitored every minute by wrist (actigraphy) to accurately calculate sleeping and waking blood pressure on an individual basis.

The results showed that those who had taken aspirin before they went to bed (at an average time of 11:00 p.m.), decreased their systolic blood pressure by an average of 5.4 mmHg and their diastolic blood pressure by an average of 3.4 mmHg over the three-month study, without any change in heart rate of physical activity compared to baseline values (p<0.001). This blood pressure reduction was similar during active hours (5.6 and 3.7 mmHg reduction in systolic and diastolic BP, p<0.001) and the nocturnal resting span (5.2 and 3.1 mmHg, respectively). Those who took a morning aspirin, usually at about 8:00 a.m., saw no reduction in ambulatory blood pressure at all, nor did participants in the HDR-only group.

“These results show us that we cannot underestimate the impact of the body's circadian rhythms," said Hermida. "The beneficial effects of time-dependent administration of aspirin have, until now, been largely unknown in people with prehypertension. Personalizing treatment according to one's own rhythms gives us a new option to optimize blood pressure control and reduce risk of cardiovascular disease down the line."

Aspirin may reduce risk of breast cancer

Taking aspirin on a daily basis may lower women’s risk of a particular type of breast cancer, according to results published in BioMed Central’s open access journal Breast Cancer Research. In this large study, aspirin use was linked to a small reduction in estrogen receptor-positive breast cancers. However, unlike in some previous research, aspirin and related painkillers were not found to reduce the total risk of breast cancer.

Around 75% of breast cancers are estrogen receptor-positive (ER+), which means the cancer cells have receptors for the female hormone estrogen on their surface. Estrogen helps the cancer cells grow, so drugs that block the action of estrogen are often used to treat ER+ cancer.

It is feasible, in theory, that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) could lower the total risk of breast cancer. They block an enzyme called cyclooxygenase, an activity that could disrupt breast cancer development in a number of ways – for example, by reducing the amount of estrogen produced in the body.

A US research team, led by Gretchen Gierach, studied over 127,000 women enrolled in the National Institutes of Health–AARP Diet and Health Study, which was designed to explore the possible links between diet, health-related behaviours and cancer in older people in the USA. For the current research, the participants were women aged 51–72 with no history of cancer.

Unlike other NSAIDs, aspirin has irreversible effects on cyclooxygenase (COX) enzymes, so the study authors looked for differences in cancer development according to whether women used aspirin or another kind of NSAID.

NSAID use was not linked to total risk of breast cancer in this study. However, when the team considered different cancer subtypes and specific types of NSAIDs, they found that daily aspirin use was associated with a small reduction (16%) in the risk of ER+ breast cancer. A similar link was not seen in cases of ER- breast cancer.

Gierach concludes: “In summary, our results do not support an important influence of NSAIDs on total breast cancer risk. Daily aspirin use, however, appeared to offer some protection for ER+ breast cancer in this population … Our results provide support for further evaluating relationships in prospective studies with well-defined measures of NSAID use by NSAID type … and by ER status.”
Aspirin can prevent liver damage that afflicts millions, Yale study finds

Simple aspirin may prevent liver damage in millions of people suffering from side effects of common drugs, alcohol abuse, and obesity-related liver disease, a new Yale University study suggests.

The study in the January 26, 2009 edition of Journal of Clinical Investigation documents that in mice, aspirin reduced mortality caused by an overdose of acetaminophen, best known by the brand name Tylenol. It further showed that a class of molecules known as TLR antagonists, which block receptors known to activate inflammation, have a similar effect as aspirin. Since these agents seem to work by reducing injury-induced inflammation, the results suggest aspirin may help prevent and treat liver damage from a host of non-infectious causes, said Wajahat Mehal, M.D., of the Section of Digestive Diseases and Department of Immunobiology at Yale School of Medicine.

"Many agents such as drugs and alcohol cause liver damage, and we have found two ways to block a central pathway responsible for such liver injury," Mehal said. "Our strategy is to use aspirin on a daily basis to prevent liver injury, but if it occurs, to use TLR antagonists to treat it."

Promising drugs that have failed clinical trials because of liver toxicity might be resurrected if combined with aspirin, Mehal said.

"This offers the exciting possibility of reducing a lot of pain and suffering in patients with liver diseases, using a new and very practical approach," Mehal said.


Coated Aspirin As Bad on Stomach as Plain Aspirin

Some people take aspirin without ever having a problem with their stomach. Others develop low-grade stomach pain or get an ulcer. A few develop gastrointestinal bleeding severe enough to require a transfusion. But coated or buffered aspirin doesn’t do much to help.

Coated aspirin, also called enteric-coated aspirin, is the pharmaceutical industry’s attempt to limit the drug’s effect on the stomach. It’s a great idea: Cover aspirin with a coating designed to withstand stomach acids so it sails through the stomach untouched and dissolves in the more neutral small intestine. Keeping aspirin intact for as long as possible might mean it won’t damage the lining of the stomach. Yet studies show that coasted aspirin has virtually the same effect on the stomach as plain, uncoated aspirin.

The Harvard Heart Letter notes that aspirin doesn’t have to be in contact with stomach cells to harm them. Even when the pill dissolves in the intestines, the medicine gets into the bloodstream and is carried to all parts of the body—including the cells lining the stomach. Once there, it blocks the COX-1 enzyme. Stomach cells need COX-1 in order to churn out compounds that protect them from the powerful acids that digest food.

Of course, we’re all different, and coated aspirin may work for some people. But be advised that coating doesn’t guarantee problem-free aspirin use.

Risks of Using Aspirin to Prevent Heart Attack Or Stroke Differ by Gender and Age

Patients and clinicians should consider risk factors-- including age, gender, diabetes, blood pressure, cholesterol levels, smoking and risk of gastrointestinal bleeding-- before deciding whether to use aspirin to prevent heart attacks or strokes, according to new recommendations from the U.S. Preventive Services Task Force. These recommendations do not apply to people who have already had a heart attack or stroke.

The recommendations are published in the March 17, 2009 issue of the Annals of Internal Medicine. The Task Force reviewed new evidence from the National Institutes of Health’s Women’s Health Study published since the last Task Force review of this topic in 2002, including a recent meta-analysis of the risks and benefits of aspirin and found aspirin may have different benefits and harms in men and women. The Task Force found good evidence that aspirin decreases first heart attacks in men and first strokes in women.

The more risk factors people have, the more likely they are to benefit from aspirin. The Task Force recommends that men between the ages of 45 and 79 should use aspirin to reduce their risk for heart attacks when the benefits outweigh the harms for potential gastrointestinal bleeding. Women between the ages of 55 and 79 should use aspirin to reduce their risk for ischemic stroke when the benefits outweigh the harms for potential gastrointestinal bleeding. Ischemic strokes occur as a result of an obstruction within a blood vessel supplying blood to the brain and are potentially prevented by aspirin use. The risk of gastrointestinal bleeding with and without aspirin use increases with age and is twice as high in men as in women. Other risk factors for gastrointestinal bleeding include upper gastrointestinal tract pain, gastrointestinal ulcers, and using non-steroidal anti-inflammatory drugs.

The Task Force recommended against using aspirin to prevent either strokes or heart disease in men under 45 or women under age 55 because heart attacks are less likely to occur in men younger than 45 and ischemic strokes are less likely to occur in women younger than 55, and because limited evidence exists in these age groups.

People age 80 and older could benefit more than younger people from aspirin because of their higher risk of cardiovascular disease, but the harms are also greater because the risk of gastrointestinal bleeding increases with age. The Task Force could not find clear evidence that the benefits of using aspirin outweigh the risks in people 80 years or older.

“The decision about whether the benefits of taking aspirin outweigh the harms is an individual one. Patients should work with their clinicians to look at their risk factors and decide if taking aspirin to lower their risk for heart attacks or strokes outweighs the potential risk of gastrointestinal bleeding,” said Task Force Chair Ned Calonge, M.D., who is also chief medical officer and state epidemiologist for the Colorado Department of Public Health and Information.

Cardiovascular disease is the leading cause of death in the United States. It is the underlying or contributing cause in approximately 58 percent of all deaths. In 2003, 1 in every 3 adults had some type of cardiovascular disease. In adults over the age of 40, the risk of developing cardiovascular disease is 2 in 3 for men and more than 1 in 2 for women.

The Task Force could not find evidence about what the optimum dose of aspirin is to prevent heart attacks or strokes. Evidence shows benefits at a range of doses, and the risk of gastrointestinal bleeding may increase with the dose. A dose as low as 75 mg seems as effective as higher doses. Taking aspirin increases a person’s chances of gastrointestinal bleeding, the sudden loss of blood or perforation of the digestive tract that can lead to hospitalization or death. Taking aspirin also increases the chance of a hemorrhagic stroke, or bleeding in the brain, which is different than the ischemic stroke that aspirin can prevent.

In 2002, the Task Force strongly recommended that clinicians discuss aspirin use with adults at increased risk for coronary heart disease and that discussions with patients should address both the potential benefits and potential harms of aspirin therapy. The new recommendation provides more specific guidance about benefits and harms to specific age groups and gender-specific benefits and provides clinicians with information on how to estimate an individual’s risks for heart disease or stroke.

The U.S. Preventive Services Task Force is an independent panel of experts in prevention and primary care. The Task Force conducts rigorous, impartial assessments of the scientific evidence for the effectiveness of a broad range of clinical preventive services, including screening, counseling and preventive medications. Its recommendations are considered the gold standard for clinical preventive services.

Summary of Recommendations

• The USPSTF recommends the use of aspirin for men age 45 to 79 years when the potential benefit due to a reduction in myocardial infarctions outweighs the potential harm due to an increase in gastrointestinal hemorrhage.

• The USPSTF recommends the use of aspirin for women age 55 to 79 years when the potential benefit of a reduction in ischemic strokes outweighs the potential harm of an increase in gastrointestinal hemorrhage.

• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of aspirin for cardiovascular disease prevention in men and women 80 years or older.

• The USPSTF recommends against the use of aspirin for stroke prevention in women younger than 55 years and for myocardial infarction prevention in men younger than 45 years.

Supporting Documents

Aspirin for the Prevention of Cardiovascular Disease, March 2009_ Recommendations and Rationale (PDF File, 335 KB; PDF Help)_ Supporting Article (PDF File, 160 KB; PDF Help) _ Evidence Synthesis (PDF File, 145 KB; PDF Help) _ Clinical Summary (PDF File, 114 KB; PDF Help

Aspirin Improves Survival in Women with Stable Heart Disease, According to WHI Study

New results from the Women’s Health Initiative (WHI) Observational Study provide additional evidence that aspirin may reduce the risk of death in postmenopausal women who have heart disease or who have had a stroke. Jacques Rossouw, M.D., chief of the Women’s Health Initiative Branch at the National Heart, Lung, and Blood Institute (NHLBI), is available to comment on these findings. NHLBI, part of the National Institutes of Health, funded the research.

The study also provides new insight into aspirin dosing for women, suggesting that a lower dose of aspirin (81 milligrams, or mg) is as effective as a higher dose (325 mg). This is good news for women who might be concerned with internal bleeding, a well-known risk of aspirin that may be more likely with higher doses of aspirin, according to other studies. However, randomized clinical trials are needed to determine the optimal doses of aspirin in women with cardiovascular disease.

“Aspirin Use, Dose, and Clinical Outcomes in Postmenopausal Women with Stable Cardiovascular Disease – The Women’s Health Initiative Observational Study,” appears in the March issue of the journal Circulation: Cardiovascular Quality and Outcomes and was published online March 5, 2009.

Scientific evidence indicates that, in general, aspirin lowers the risk of death and incidence of heart attack and stroke in patients with a history of cardiovascular disease; however, the benefits of aspirin in women with stable cardiovascular disease in particular are unknown. In this study, researchers analyzed data from 8,928 postmenopausal women who had previously had a heart attack, stroke or transient ischemic attack (TIA, or mini-stroke), angina, or angioplasty or coronary bypass surgery to improve blood flow. Participants were followed for an average of 6.5 years.

Compared to those who did not report taking aspirin, regular aspirin users had a 25 percent lower risk of death from cardiovascular disease and a 14 percent lower risk of death from any cause. Overall, aspirin use did not significantly decrease the risk of heart attack, stroke, or other cardiovascular events, except among women in their seventies. There were no significant differences in death rates or other outcomes between women taking 81 mg of aspirin compared to those taking 325 mg.

The size of the WHI Observational Study and the diversity of participants provide valuable insight into the use of medications in the primary care setting. For example, the study found that only 46 percent of women with stable cardiovascular disease in the study reported taking aspirin regularly, despite current guidelines recommendations. In addition, subgroup analyses indicate that black women and women with Medicaid insurance were less likely to use aspirin as recommended, compared to women of other ethnic groups and insurance status.

The WHI is a major, 15-year research program designed to address the most frequent causes of death, disability, and poor quality of life in postmenopausal women: cardiovascular disease, cancer, and osteoporosis. The WHI Observational Study is a nationwide, prospective study to examine the association between clinical, socioeconomic, behavioral, and dietary risk factors and the subsequent incidence of several health outcomes. The Observational Study followed 93,676 postmenopausal women between the ages of 50 and 79 for an average of 8 years. Participants filled out health forms and visited their clinic physician periodically; participants were not required to take any medication or change their health habits.


Benefits of aspirin for treating osteoporosis

Researchers at the University of Southern California, School of Dentistry have uncovered the health benefits of aspirin in the fight against osteoporosis. Forty-four million Americans, 68 percent of whom are women, suffer from the debilitating effects of osteoporosis according to the National Institute of Health. One out of every two women and one in four men over 50 will have an osteoporosis-related fracture in their lifetime.

This latest study identifies aspirin's medicinal role on two fronts. In mice, the drug appears to prevent both improper bone resorption and the death of bone-forming stem cells. The findings will be published in PLoS ONE http://www.plosone.org/doi/pone.0002615 on Wednesday, July 9, 2007.

An aspirin regimen appears to help mice recover from osteoporosis in two useful ways, striking a balance between bone formation and resorption, according to Associate Professor Songtao Shi and Research Associate Takayoshi Yamaza of the USC School of Dentistry's Center for Craniofacial Molecular Biology (CCMB).

The silent disease affects both men and women. In women, bone loss is greatest during the first few years after menopause. Osteoporosis occurs when bone resorption (loss of bone) occurs too quickly or when formation (replacement) occurs to slowly.

According to Shi, the removal of the ovaries and the resulting decrease in estrogen induces osteoporosis in mice, much like the onset of the disease in post-menopausal women. It is commonly thought that T-lymphocytes, a type of immune system cell, play a pivotal part in this process by over-activating osteoclasts, the bone cells that reabsorb bone material from the skeleton. Most current osteoporosis therapies aim to curb overactive osteoclasts.

However, there seems to be another side to the T-lymphocytes', or T-cells', role in osteoporosis, Yamaza says. While the immune cells typically attack disease cells and other foreign entities, the T-cells can mistakenly attack healthy stem cells.

"After infusing the mice with T-cells, the T-cells impaired the function of bone marrow mesenchymal stem cells as well as caused osteoclast numbers to increase," he says.

The bone marrow mesenchymal stem cells, or BMMSC, differentiate to become many different cells including osteoblasts, the cells responsible for bone formation. If this processed is impaired by T-cells, bone formation cannot keep up with bone resorption caused by osteoclasts, and bone mineral density decreases – the hallmark of osteoporosis that leads to skeletal structural deterioration and fractures.

An aspirin regimen has been linked in earlier epidemiological studies to better bone mineral density, but the mechanisms of its interactions in regards to bone health had not yet been studied extensively, Shi said.

"We've shown how aspirin both inhibits bone resorption and promotes osteoblast formation," Shi says.

Another exciting aspect of the aspirin treatment is that the dose administered to the mice in order to increase their bone mineral density is the same as that of a typical human aspirin regimen when adjusted for body weight differences, he adds. While the species difference is still a factor, the results are promising.

"When we gave a large amount of aspirin to the mouse by injection, it did not work," Shi says, "but when we gave a low dose in the mice's water for a long period of time, similar to a human dosage, the bone mineral density increased."

Shi and Yamaza hope that their work will translate into new clinical strategies for osteoporosis.

"We have opened a door," Shi says. "We hope other scientists can confirm what we've found and move the treatment forward."

The use of aspirin offers hope to patients and doctors searching for a potential alternative to bisphophonates currently being used as a means of prevention and treatment for osteoporosis. This latest study opens up the possibility that aspirin some day will not only be prescribed to ward off heart disease but also osteoporosis.

Aspirin reduces the risk of colorectal cancer.

A study of Medicare patients with osteoarthritis provides additional evidence that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin reduce the risk of colorectal cancer. Earlier investigations of the drugs’ impact on tumor development could not rule out the possibility that an observed protective effect was caused by other preventive health care measures. The current study, led by a Massachusetts General Hospital (MGH) physician, appears in the August 2007 Journal of General Internal Medicine.

“This is good news for people who take NSAIDs regularly for osteoarthritis,” says Elizabeth Lamont, MD, MS, of the MGH Cancer Center, the study’s lead author. “Although patients face risks such as bleeding or kidney damage from this therapy, they probably are at a lower risk of developing colorectal cancer.” Because of the risks posed by the dosage used to treat osteoarthritis, she and her co-authors stress that currently available NSAIDs should not be used solely to prevent cancer.

Earlier randomized trials clearly showed that NSAID treatment can prevent the development of precancerous colorectal polyps, but whether or not such therapy also reduces the risk of invasive colorectal cancer has not yet been confirmed. Those trials used relatively low doses of aspirin and showed no significant differences in colorectal cancer rates between the aspirin and placebo groups. While many observational studies have shown a protective effect of NSAIDs against colorectal cancer, interpretation of some of those results may have been clouded by other healthy behaviors of the participants.

“It would be ideal to conduct a randomized clinical trial – in which half the patients receive NSAIDs at doses higher than those used in prior trials and half receive placebos – and follow both groups for many years for evidence of cancer. But such trials are expensive, time consuming, and could present real health risks to participants. Therefore, we took advantage of a natural ‘experiment’ by comparing data from patients known to regularly take higher amounts of NSAIDs with that from those taking lower doses in order to evaluate any effect on colorectal cancer risk.”

First the researchers reviewed data from the 1993-94 National Ambulatory Medical Care Survey, in which physicians report on the diagnoses of and treatments prescribed to patients seen during a randomly selected week. Those results verified that older patients with osteoarthritis were more than four times as likely to take NSAIDs as were those without osteoarthritis. They then analyzed information from the Survival Epidemiology and End-Results (SEER)-Medicare program, studying groups of elderly Medicare patients with and without colorectal cancer, to search for associations with NSAID use.

Comparing information on 4,600 individuals with colorectal cancer to data from 100,000 controls, they found that a history of osteoarthritis was associated with a 15 percent reduction in the likelihood of a colorectal cancer diagnosis. A similar association was seen when total knee replacement was used as a marker for NSAID treatment.

“The magnitude of colorectal cancer risk reduction between patients with and without osteoarthritis is completely consistent with the risk reduction for pre-cancerous polyps reported in clinical trials of NSAIDs,” Lamont says. “Confirming this association supports the need for further research to identify NSAID agents safe enough to be used for regular, preventive therapy by the general population.”

Benefits of aspirin to prevent colon cancer

A colon cancer researcher at the Ireland Cancer Center of University Hospitals Case Medical Center (UHCMC) has laid out the roadmap for how medical science should employ aspirin and new aspirin-like drugs for use in preventing colon cancer in certain high-risk individuals.

In the New England Journal of Medicine, (May, 2007) Sanford Markowitz, MD, PhD, writes an editorial accompanying research from Dr. Charles Fuchs' team at Harvard Medical School that lays out the hypothesized mechanism by which the use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), also called COX-2 inhibitors, act to decrease the risk of developing colon cancer.

"The compelling evidence that chronic use of aspirin or certain NSAIDS can substantially lower the risk of colon cancer has important implications, especially because colon cancer is the second leading cause of cancer death," writes Dr. Markowitz, the Francis Wragg Ingalls Professor of Cancer Genetics at UHCMC and Case Western Reserve University School of Medicine.

In the Journal article, the Harvard researchers' findings demonstrated that two-thirds of colon cancers have high levels of expression of the COX-2 enzyme, which is blocked by aspirin. Individuals who regularly used aspirin over a course of several years demonstrated a 36% decrease in the risk of developing one of these high COX-2 expressing colon cancers. These results again demonstrated that drugs that block COX-2 can decrease the risk of colon cancer, and demonstrated that such drugs specifically target those individuals whose tumor development is encouraged by the action of the COX-2 enzyme.

Dr. Markowitz' accompanying editorial maps out those studies which will be required to determine the potential use of aspirin in prevention of colon cancer and to determine which individuals might benefit most from taking aspirin or aspirin-like drugs (NSAIDS) such as ibuprofen and Celebrex. Finally, the editorial outlines potential targets for development of drugs that might provide similar protection as aspirin or COX-2 inhibitor drugs for developing colon cancer but with a lesser risk of adverse side effects.

"Interventional trials have shown a decreased risk of the development of colon cancer in high-risk subjects who were given aspirin or COX-2 selective NSAID inhibitors and observational trials have associated a decreased risk of colon cancer with aspirin use," writes Dr. Markowitz in the editorial. "The researchers' findings provide powerful support for the role of COX-2 as a key mediator in the development of colon cancer and now pose questions about the biologic basis and clinical applications of discovering differences that express high or low levels of COX-2."

Dr. Markowitz has done seminal research in the field of colon cancer genetics and prevention. Among his numerous research articles, he published a study on the findings of a new "Celebrex-like" gene that suppresses the grown of colon cancer in the July 2006 issue of Proceedings of the National Academy of Sciences. Dr. Markowitz likens the gene, called 15-PGDH, to a naturally occurring Cox-2 inhibitor such as Celebrex. These findings may lead to the development of a new drug for colon cancer prevention.

"Sandy and his research team have made great strides in colon cancer prevention," says Stanton Gerson, MD, Director of the Ireland Cancer Center at University Hospitals Case Medical Center as well as the Case Comprehensive Cancer Center. "This editorial and all of his proceeding work may have great impact on individuals at high risk for developing this deadly disease."


Aspirin Better Heart Treatment for Men than Women

A new study shows that aspirin therapy for coronary artery disease is four times more likely to be ineffective in women compared to men with the same medical history.

Historically, studies have shown that aspirin therapy is less effective in women than in men, but it has remained unclear how much less effective and whether this affects patient outcomes, said Michael Dorsch, clinical pharmacist and adjunct clinical instructor at the University of Michigan College of Pharmacy.

Dorsch is the lead author of the paper, "Aspirin Resistance in Patients with Stable Coronary Artery Disease," which appears online tin the Annals of Pharmacotherapy.

Originally, Dorsch and his team set out to determine if patients with a history of heart attacks were more apt to be aspirin resistant than those with coronary artery disease but no history of heart attack. They found that gender and not medical history was a predictor for aspirin resistance, Dorsch said. The results surprised him.

"I was surprised by how big of a difference it was for females," said Dorsch, who has appointments at the U-M Health System and the U-M College of Pharmacy, and started the study as a resident at the University of North Carolina. "This is another piece of information that affirms we need more studies in women."

Aspirin therapy is a cornerstone in managing heart disease because it inhibits blood clotting. Aspirin therapy can reduce the risk of a nonfatal heart attack or stroke by about 23 percent, and an estimated 20 million men and women take a low dose of aspirin (81-325 mg daily) to control heart disease. But despite its effectiveness, there is evidence that aspirin is less effective in some patients, and researchers don't really know why. This can be frightening because most doctors do not check for aspirin resistance before prescribing aspirin therapy and therefore presume it's working in the patient when it may not be, he said.

There isn't enough evidence to show if people who are aspirin resistant can simply take larger doses, but Dorsch warns that people taking aspirin on the advice of a doctor shouldn't stop therapy on account of these results.

Not only did the study quantify how much more effective aspirin therapy is for men than for women, it is also the first study that Dorsch knows of to measure aspirin resistance in men and women with stable coronary artery disease. Previous studies have looked at the impact of aspirin therapy on people who have had a heart attack.

For the study, researchers randomly selected 100 patients who were visiting their cardiologist for a regularly scheduled appointment. All had coronary artery disease but only half had a history of heart attack. Researchers used a device called VerifyNow Aspirin Assay to test the percentage of platelet reactivity after blood samples were exposed to a chemical that causes clotting.

Aspirin works by causing platelet inhibition in the blood, which means that platelets cannot stick together and this slows the formation of blood clots that cause a heart attack or stroke.

"This does happen in women, but it doesn't happen in as many women and it's not as effective," Dorsch said. The testing device uses an optical sensor to "see" what percentage of the platelets in the blood sample clump together. Anything less than 40 percent platelet inhibition is considered aspirin resistant.

"We really don't know the mechanism," Dorsch said. "It could be that women have a more active platelet system in the body so it's less likely that platelet action would be inhibited."

In the future, researchers hope to look at aspirin therapy outcomes in women only and see if those outcomes can be changed. The majority of testing for aspirin therapy has been on men, so not much is known about how women respond.

"Heart disease is the number one killer of women in the United States. Future research should be aimed at finding out the cause of this increase in aspirin resistance and the effect on outcomes in women with heart disease." Dorsch said.

Aspirin Fights Cancer

A daily dose of adult-strength aspirin may modestly reduce cancer risk in populations with high rates of colorectal, prostate, and breast cancer if taken for at least five years.

The Women's Health Study trial recently reported that long-term use of low-dose aspirin (about 100mg every other day) does not reduce a woman's cancer risk, but it did not examine whether high doses of aspirin have an effect on cancer risk.

Eric Jacobs, Ph.D., of the American Cancer Society in Atlanta, and colleagues looked for associations between long-term daily aspirin use (at least 325mg/day) and cancer incidence in a group of nearly 70,000 men and 76,000 women. Aspirin use was determined by a questionnaire.

During the 12 year follow-up, nearly 18,000 men and women in the study were diagnosed with cancer. The researchers found that daily use of adult-strength aspirin for at least five years was associated with an approximately 15 percent relative reduction in overall cancer risk, though the decrease was not statistically significant in women. Additionally, aspirin use was associated with a 20 percent reduced risk of prostate cancer and a 30 percent reduced risk of colorectal cancer in men and women, compared to people who didn't take aspirin. There was no effect on risk in other cancers examined—lung cancer, bladder cancer, melanoma, leukemia, non-Hodgkins lymphoma, pancreatic cancer, and kidney cancer. Aspirin use for less than five years was not associated with decreased cancer risk.

"Our results do not have immediate clinical implications. Confirmation from randomized trials is necessary before a reduction in cancer risk could be considered a benefit of using adult-strength aspirin. Our results indicate that a randomized trial examining the effect of aspirin on cancer incidence would need to be both large and long term, probably lasting a minimum of 10 years. More evidence is needed before any such trial can be justified," the authors write.

In an accompanying editorial, Maria Elena Martinez, Ph.D., of the Arizona Cancer Center in Tucson, and E. Robert Greenberg, M.D., of the Fred Hutchinson Cancer Center in Seattle, write that, for the average person, the side effects of daily long-term aspirin use, such as intestinal bleeding or stroke, might outweigh the its benefits of cancer prevention. "However, if aspirin were shown to truly prevent a multitude of common cancers, there might be clinical situations in which daily adult-strength aspirin would be indicated," the authors write.

Long-term aspirin = reduced risk of dying in women


Women who take low to moderate doses of aspirin have a reduced risk of death from any cause, and especially heart disease–related deaths, according to a report in the March 26, 2007 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Some studies have provided evidence that aspirin may reduce the risk of heart disease and some types of cancer, the two leading causes of death in U.S. women, according to background information in the article. However, it is unclear whether aspirin reduces the risk of death overall for women.

Andrew T. Chan, M.D., M.P.H., Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues examined the association between aspirin use and death in 79,439 women enrolled in the Nurses’ Health Study, a large group of female nurses who have been followed since 1976. Beginning in 1980 and again every two years through 2004, the women were asked if they used aspirin regularly and if so, how many tablets they typically took per week. At the beginning of the study, the women had no history of cardiovascular disease or cancer.

A total of 45,305 women did not use aspirin; 29,132 took low to moderate doses (one to 14 standard 325-milligram tablets of aspirin per week); and 5,002 took more than 14 tablets per week. By June 1, 2004, 9,477 of the women had died, 1,991 of heart disease and 4,469 of cancer. Women who reported using aspirin currently had a 25 percent lower risk of death from any cause than women who never used aspirin regularly. The association was stronger for death from cardiovascular disease (women who used aspirin had a 38 percent lower risk) than for death from cancer (women who used aspirin had a 12 percent lower risk).

"Use of aspirin for one to five years was associated with significant reductions in cardiovascular mortality," the authors write. "In contrast, a significant reduction in risk of cancer deaths was not observed until after 10 years of aspirin use. The benefit associated with aspirin was confined to low and moderate doses and was significantly greater in older participants and those with more cardiac risk factors."

There are several mechanisms by which aspirin could reduce the risk of death, the authors note. "Aspirin therapy may influence cardiovascular disease and cancer through its effect on common pathogenic pathways such as inflammation, insulin resistance, oxidative stress [damage to the cells caused by oxygen exposure] and cyclooxygenase (COX) enzyme activity," also linked to inflammation, they write.

Because the study looked at women who made the decision themselves whether or not to take aspirin, as opposed to a clinical trial where women are randomly assigned to aspirin or a placebo, the results do not suggest that all women should take aspirin. "Nevertheless, these data support a need for continued investigation of the use of aspirin for chronic disease prevention," the authors conclude.

These findings differ from the results of other studies regarding the benefits of aspirin use in healthy women, leaving confusion about aspirin’s role, writes John A. Baron, M.D., Dartmouth Medical School, Lebanon, N.H., in an accompanying editorial.

Dr. Baron points out that in the Women’s Health Study, researchers followed almost 40,000 women for 11 years and did not find any reduced risk of cardiovascular or other death associated with aspirin therapy, in contrast to the dramatic risk reduction seen in the Nurses’ Health Study. "Is aspirin really that good or is there some other explanation for the findings that differ so much from those of the WHS and other primary prevention trials?" he writes.

"The difference between the NHS and the aggregated data from the WHS and other trials is too large to be explained by potential weaknesses in the randomized studies," Dr. Baron writes. "At the same time, one has to consider that the observational NHS may not have been able to deal with the differences between aspirin users and non-users."

"Therefore, these new findings by Chan et al cannot overcome the accumulated evidence that aspirin is not particularly effective for the primary prevention of death from cardiovascular disease in women," he concludes.

NSAIDs (except aspirin) increase risk for heart attack and stroke

American Heart Association Scientific Statement

Many doctors should change the way they prescribe pain relievers for chronic pain in patients with or at risk for heart disease based on accumulated evidence that nonsteroidal anti-inflammatory drugs (NSAIDs), with the exception of aspirin, increase risk for heart attack and stroke, according to an American Heart Association statement published in Circulation: Journal of the American Heart Association. (February, 2007)

"We believe that some physicians have been prescribing the new COX-2 inhibitors as the first line of treatment. We are turning that around and saying that, for chronic pain in patients with known heart disease or who are at risk for heart disease, these drugs should be the last line of treatment," said Elliott M. Antman, M.D., FAHA, lead author of the American Heart Association scientific statement and Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital.

"We advise physicians to start with non-pharmacologic treatments such as physical therapy and exercise, weight loss to reduce stress on joints, and heat or cold therapy. If the non-pharmacologic approach does not provide enough pain relief or control of symptoms, we recommend a stepped-care approach when it comes to prescribing drugs," he added.

"Take into account the patient's health history and consider acetaminophen, aspirin and even short-term use of narcotic analgesics as the first step. If further relief is needed, physicians should suggest the least selective COX-2 inhibitors first, moving progressively toward more selective COX-2 inhibitors, which are at the bottom of the list, only if needed. All drugs should be used at the lowest dose necessary to control symptoms and prescribed for the shortest time possible."

Drugs in the NSAIDs class work by inhibiting cyclooxygenase (COX), an enzyme system that comes in two major forms: COX-1, which the body produces constantly in most tissues, and COX-2, produced during the body's inflammatory response. Because COX-1 is also protective of the gastrointestinal (GI) tract, long-term use of drugs that suppress COX-1, such as aspirin, have been associated with gastrointestinal complications, including ulcers. "Selective" COX-2 inhibitors were developed to avoid the GI complications of traditional NSAIDs, not because they had advantages in terms of pain relief,

Antman explained. However, multiple studies have indicated an increased risk of cardiovascular disease (CVD) complications from COX-2 selective NSAIDS, particularly in patients with prior CVD or risk factors for CVD.

"Recent studies indicate that the cells lining the blood vessels have more of the COX-2 enzyme than initially thought. So it's possible that inhibiting the COX-2 pathway can make a person's blood more likely to clot. There is also an increase in sodium and water retention, which in turn could worsen heart failure and produce high blood pressure," Antman explained. "The more you inhibit COX-1, the greater the increase in GI risk; the more you inhibit COX-2 the greater the cardiovascular risk."

The scientific statement comes two years after the association released the last one on the issue. It was prompted, in part, by new analyses indicating that the increased cardiovascular risk associated with COX-2 selective NSAIDs may also extend to less selective traditional NSAIDs.

The statement includes details from a meta-analysis indicating that, compared with placebo, COX-2 selective drugs seem to increase the risk of a heart attack by about 86 percent. The statement also points out that two common NSAIDs traditionally thought of an non-selective – diclofenac and ibuprofen – appear to increase the relative risk of cardiovascular disease. In the last two years, the U.S. Food and Drug Administration (FDA) added warning statements to NSAIDs, other than aspirin, pointing out the increased risk for cardiovascular events.

One non-selective NSAID, naproxen, did not seem to increase CVD risk in these analyses. However, Antman pointed out that although naproxen appeared safer than the other NSAIDs, relatively few studies have been done with naproxen and doctors should continue to be cautious about prescribing it as well, pending more information.

"This is a fast-moving field with new information available from multiple sources. We feel the most important thing the American Heart Association can do is to give practical advice to clinicians who treat cardiac patients with pain every day," said Antman.

Because there are so many drugs in the NSAID class and because they can affect either COX-1 or COX-2 or both, it is very important to know where a given drug falls in the range of selectivity, particularly when evaluating the results of head-to-head comparisons of different drugs, Antman said. The statement contains guidance that helps doctors see where individual drugs lie on the continuum of COX-1 versus COX-2 selectivity.

Selective COX-2 inhibitors have been in the news since the FDA removed the selective COX-2 inhibitor, rofecoxib, from the market in 2004. Since then, other COX-2 selective drugs have been removed from the market in the United States and other countries. One selective COX-2 inhibitor, celecoxib, remains on the market, but warnings on it were strengthened and the FDA advised that patients with a history of CVD or risk factors for CVD should be informed of the possibility of increased risks from long-term use, Antman said.

Aspirin saves lives of cancer patients suffering heart attacks, despite fears of bleeding

Many cancer patients who have heart attacks often are not treated with life saving aspirin given the belief in the medical community that they could experience lethal bleeding. Researchers at The University of Texas M. D. Anderson Cancer Center, however, say that notion is now proven wrong and that without aspirin, the majority of these patients will die.

Researchers say that their study, to be published in the February 1, 2007 issue of the journal Cancer and now available online, turns common medical assumptions upside down and will likely change medical practice for cancer patients. Because aspirin can thin blood and cancer patients experience low platelet counts and abnormal clotting, physicians view aspirin as a relative contraindication. Given that blood platelets are responsible for the clotting process, physicians do not eagerly prescribe aspirin as a standard treatment.

In this study, however, the investigators found that 9 of 10 cancer patients with thrombocytopenia (low platelet count) who were experiencing a heart attack and who did not receive aspirin died, whereas only one patient died in a group of 17 similar cancer patients who received aspirin. They also found aspirin helps cancer patients with normal platelet count survive heart attacks, just as it does for people without cancer.

"The notion that heart attacks in patients with low platelets should be treated with clot-dissolving aspirin defies logic, that is unless you suspect that the cancer is interfering with platelet function," says the study's senior investigator and author, Jean-Bernard Durand, M.D., assistant professor in the Department of Cardiology at M. D. Anderson Cancer Center.

"We believe tumors may be releasing chemicals that allow the cancer to form new blood supplies which makes blood more susceptible to forming clots." Durand, a heart failure specialist, says. "There appears to be a platelet paradox suggesting that cancer may affect the mechanism of the way that blood clots, and from this analysis, we have found that the single most important predictor of survival in these patients is whether or not they received aspirin." Durand says more research is needed to better understand this contraindication.

According to the World Health Organization there are approximately 10 million cancer patients worldwide, of which 1.5 million may develop blood clots during their cancer treatment and, as such, are at a much higher risk of dying from heart disease if not treated properly. "Now that we have this study, it would be a travesty if you survive treatment for cancer only to die of a heart attack soon thereafter," Durand says.

According to Durand, no guidelines currently exist for treatment of heart attacks in patients with cancer. He says that physicians are especially perplexed about what to do for cancer patients with thrombosis (blood clots), a condition that affects about 15 percent of all cancer patients and can be due to the use of chemotherapy or the presence of cancer.

Durand came to M. D. Anderson in 2000 to start the Cardiomyopathy Services, which is believed to be the only program in the world specifically designed to look at cardiovascular complications caused by chemotherapy treatment. He is also the co-founder of CONQUER (Cardiology Oncology International Quest to Educate and Research Heart Failure in Cancer), a newly created organization with goals of increasing the success of chemotherapy by reducing cardiovascular disease as a barrier and long term risk.

He and anesthesiologist Mona Sarkiss, M.D., Ph.D., made the observation that patients with thrombocytopenia who suffered a heart attack and were being treated in the intensive care unit at M. D. Anderson tended to die more often when they were not given aspirin. However, they noted that some of the patients given aspirin and/or beta-blockers had "great" clinical outcomes. "Because no practice guidelines exist, physicians were treating their patients with great variability and the disparity was obvious," Durand says.

Sarkiss, who is the study's lead author, Durand, and a team of researchers which included investigators from Baylor College of Medicine and Duke University Medical Center, conducted a retrospective analysis of cancer patients treated for heart attacks at M. D. Anderson Cancer Center in 2001. These 70 patients were divided into two groups based on their platelet counts, and data was collected on the use of aspirin, bleeding complications, and survival.

They found that heart attack patients with low platelets who did not receive aspirin had a seven-day survival rate of 6 percent, compared with 90 percent survival in those who received aspirin. Dr. Durand notes that there were no severe bleeding complications in patients who used aspirin. Conversely, patients with low platelet counts who formed a blood clot and were not exposed to aspirin died.

The beneficial effect of aspirin also was seen in patients with normal platelet counts. Seven-day survival was 88 percent in aspirin-treated patients as compared to 45 percent in patients who did not receive aspirin, the researchers found.

Durand observed that these deaths rates are abnormally high. "In the non-cancer patient with acute coronary syndrome anywhere in the United States, an expected seven-day mortality is less than 1 percent," he says.

There were parallel findings for those patients in either group who were treated with beta-blockers, which block the heart's use of adrenalin. The protective effect was not as strong as seen with aspirin, but was still life saving.

In those patients with a normal platelet count, 91 percent survived seven days when treated with beta-blockers, whereas 36 percent survived if they were not treated with the agent. In the thrombocytopenic group, 73 percent survived seven days when treated with beta-blockers, whereas only 13 percent survived if they were not treated.

Low-dose aspirin offers lower chance of asthma

In a large, randomized, placebo-controlled study of 22,071 healthy male physicians, taking a low-dose of aspirin every other day lowered the risk of receiving an initial asthma diagnosis by 22 percent.

These findings, based on data from the double-blind Physicians' Health Study, appear in the second issue for January 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Tobias Kurth, M.D., Sc.D., of the Division of Aging at Brigham and Women's Hospital in Massachusetts, and five associates studied physicians, ages 40 to 84, over a period of 4.9 years. Among the 11,037 individuals who took aspirin, 113 new cases of asthma were diagnosed, as contrasted to 145 in the placebo group.

Asthma is a chronic inflammatory disease that causes potentially reversible obstructive lung problems. Breathing difficulties from asthma usually occur during "attacks," which involve narrowing of the airways, swelling of the lining, tightening of respiratory muscles and an increased secretion of mucus. In 2004, more than 20 million Americans were estimated to have asthma.

"Aspirin reduced the risk by 22 percent of newly-diagnosed adult-onset asthma," said Dr. Kurth. "These results suggest that aspirin may reduce the development of asthma in adults. They do not imply that aspirin improves symptoms in patients with asthma."

"Indeed, asthma can cause severe bronchospasm in some patients who have asthma," he continued. "Because asthma was not the primary endpoint of the U. S. Public Health Service study, additional randomized trials would be helpful to confirm the apparent reduction in asthma incidence caused by aspirin."

The Physicians Health Study, which began in 1982, was terminated after 4.9 years when results showed a 44-percent reduction in the risk of a first heart attack among those randomly assigned to aspirin.

"Physicians could self-report an asthma diagnosis on questionnaires at baseline, at six months and annually thereafter," said Dr. Kurth. "Asthma was not the original deductive endpoint of the trial."

According to the authors, the 22-percent lower risk of newly-diagnosed asthma among those assigned to the low-dose aspirin group was not affected by participant characteristics like smoking, body mass index or age.

They noted that aspirin-intolerant asthma, a problem in which aspirin exacerbates the disease, affects only a small minority of asthma patients. In three large population-based studies, that difficulty affected only four to 11 percent of the groups. In children, however, the proportion affected by aspirin intolerant asthma was significantly smaller.