Aspirin Fails Again for Primary Prevention

Aspirin Fails Again for Primary Prevention
By Crystal Phend, Staff Writer, MedPage Today
Published: October 16, 2008
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco Earn CME/CE credit
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DUNDEE, Scotland, Oct. 16 -- Aspirin is ineffective for primary prevention of cardiovascular events even in high-risk diabetics, researchers found.

Among patients with diabetes and asymptomatic peripheral arterial disease, aspirin did not reduce primary fatal and non-fatal cardiovascular events compared with placebo (hazard ratio 0.98, 95% confidence interval 0.76 to 1.26), reported Jill Belch, M.D., of the University of Dundee here, and colleagues online in BMJ.

Rates of death from stroke or coronary artery disease were similar between the groups in the randomized trial. The trial, which also looked at coronary disease and antioxidants, found no benefit in primary prevention for that intervention either.

This should come as little surprise, commented William R. Hiatt, M.D., of the University of Colorado in Denver, in an accompanying editorial.


Six other well-controlled trials, including the Women's Health Study and Physicians' Health Study, have shown no benefit for aspirin in primary prevention even for at-risk patients despite the well-established benefits in secondary prevention, he said.


"The mechanisms of this differential response to aspirin are not known," he wrote, "but clearly suggest that patients who respond to aspirin must have a history of clinical, symptomatic cardiovascular disease."


Dr. Hiatt was part of the FDA panel that in 2003 rejected labeling aspirin for primary prevention, citing universally negative primary prevention trials, which also failed to show a significant benefit for high-risk populations, including diabetics.


Although aspirin is cheap, universally available, and recommended in American Heart Association guidelines, the evidence just isn't there for patients without established symptomatic cardiovascular disease, he said.


AHA guidelines recommend aspirin for primary prevention in diabetes on the basis of a reduction of events in a mixed group of patients with and without cardiovascular disease in the Early Treatment of Diabetic Retinopathy Study.


"The assumption is that the positive findings of aspirin in patients with symptomatic coronary or cerebrovascular disease can be extrapolated to these high-risk populations without clinical evidence of cardiovascular disease," Dr. Hiatt said.


The reason for the lack of efficacy wasn't that risk was too low to see a benefit in asymptomatic patients, he noted.


"These results support the concept that risk assessment alone cannot predict which patients will benefit from aspirin," Dr. Hiatt said, again emphasizing that the only predictor of clinical response to aspirin is a history of a major coronary or cerebral ischemic event.


The multicenter trial included 1,276 Scottish adults ages 40 and older with type 1 or 2 diabetes and peripheral arterial disease indicated by an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease.


The overall risk for their age was particularly high with an event rate of about 3% a year.


Patients were randomized to double blind treatment in a two-by-two factorial design to either one 100-mg aspirin tablet daily or placebo and either one daily antioxidant capsule -- containing vitamins E, B3, B6, and C, zinc, and selenium -- or placebo.


After an average 6.7 years of follow-up, the rate of the composite primary endpoint of death from coronary heart disease or stroke, non-fatal MI or stroke, and amputation for critical limb ischemia was similar between groups.


Aspirin did not prevent these fatal and nonfatal events compared with placebo (18.2% versus 18.3%, HR 0.98, 95% CI 0.76 to 1.26). Nor was there any benefit in this outcome with antioxidants compared with placebo (18.3% versus 18.2%, HR 1.03, 95% CI 0.79 to 1.33).


For the secondary outcome of death from coronary heart disease or stroke, aspirin was not preventive compared with placebo (6.7% versus 5.5%, HR 1.23, 95% CI 0.79 to 1.93).


Daily antioxidants did not affect coronary heart disease- and stroke-related mortality compared with placebo (6.6% versus 5.7%, HR 1.21, 95% CI 0.78 to 1.89).


All-cause mortality, though, was significantly higher with the antioxidants (P=0.006). The researchers said this was partly because of a lower-than-expected death rate in the placebo group compared with an age- and sex-matched Scottish population and partly because of a relative excess of deaths in the antioxidant group.


No significant interaction between aspirin and antioxidants emerged for either the composite primary endpoint (P=0.88) or for death from coronary heart disease or stroke (P=0.95).


No significant benefits from either treatment were seen for any subgroups by age, sex, or ankle brachial pressure index.


The study was powered to rule out any clinically important benefits, Dr. Belch's group noted.


Both treatments were well tolerated with no excess in adverse events except for more gastrointestinal side effects with antioxidants, including dyspepsia (P=0.015).


However, both Dr. Hiatt and the researchers cautioned that aspirin is not without risks.


The number needed to treat to cause an adverse event, including gastrointestinal bleeding, has been estimated at 248, Dr. Belch and colleagues said.



The study was supported by a grant from the Medical Research Council. Bayer donated the aspirin and placebo tablets; Scotia Pharmaceuticals (formerly Cardinal) provided the antioxidant capsules and matching placebo.
The researchers reported no conflicts of interest.

Dr. Hiatt reported serving on the FDA cardiovascular and renal drugs advisory committee that reviewed aspirin in 2003.




Primary source: British Medical Journal
Source reference:
Belch J, et al "The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease" BMJ 2008; 337:a1840.

Additional source: British Medical Journal
Source reference:
Hiatt WR "Aspirin for prevention of cardiovascular events" BMJ 2008; 337.

Diabetes aspirin use questioned

Aspirin should not routinely be used to prevent heart attacks in people with diabetes, Scottish research suggests.

The British Medical Journal reported that in 1,300 adults with no symptoms of heart disease the drug, which can cause stomach bleeds, had no benefit.

The findings contradict many guidelines which advocate people with diabetes use aspirin to counter the underlying high risk of heart attack and stroke.

But there are key high-risk groups who still need the drug, experts said.

Patients with concerns are advised to consult their GP before changing medication.

In people who have already had a heart attack or stroke, or have been diagnosed with coronary artery disease, aspirin has been shown to reduce the risk of future "events" by around 25%.

However, in recent years doctors have begun to focus on people who have not yet developed so-called cardiovascular disease, but are at high-risk of having it in the future - such as people with diabetes.

There are around two million people over 40 with diabetes in the UK.

Around 80% of people with diabetes die of cardiovascular disease including strokes and heart attacks.

A daily dose of aspirin is recommended by several UK guidelines as a "preventive" treatment in these groups.

No benefit

But in the latest study in adults over 40 years with type 1 or type 2 diabetes and no symptoms of cardiovascular disease, there was no difference over seven years in heart attacks or strokes between those given aspirin and those given a dummy pill.

Study leader Professor Jill Belch, from the University of Dundee, said aspirin was one of the most common causes of hospital admission for gastrointestinal bleeding.

"We have got a bit ahead of ourselves with aspirin.

"We need to think again about using it for primary prevention."

However she stressed the drug was beneficial in people who had already had a heart attack or stroke.

Professor Peter Sever, an expert in clinical pharmacology and therapeutics at Imperial College London, said the study was "extremely important".

"It confirms many concerns we have that aspirin is very widely used in the general population without an evidence base to support its overall benefits.

"Thousands of people buy aspirin over the counter - I'm forever saying to patients you shouldn't be taking this.

"I have had a couple of patients admitted to hospital with major gastrointestinal bleeding when there was no evidence it was doing any good."

The number of people diagnosed with diabetes and as having a high risk of cardiovascular disease is set to increase, with government plans in England to introduce a national screening programme for the over-40s next year.

Professor Steve Field, chair of the Royal College of GPs, said it would be worth revisiting the guidelines.

"But patients shouldn't panic or stop taking aspirin," he said.

Judy O'Sullivan, cardiac nurse at the British Heart Foundation, said: "This study adds weight to the evidence that aspirin should not be prescribed to prevent disease of the heart and circulation to people with diabetes, and other high risk groups, who do not already have symptoms of the disease."

Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/1/hi/h ... 673587.stm

Published: 2008/10/17 09:37:45 GMT

© BBC MMVIII

........................ He read many books on health. Died of a typo. ....................

Goofproof wrote:Good One, Rooster! Maybe if we made Aspirin a branded prescription drug if would be more effective! Surely increasing the price to $120 a bottle, would make it work better, especally in the journals. I was taking mine before, during and after the Heart attact, it didn't stop it from happening, but I'm still here. at the cost of Aspirin, why not use it. It can be abused as can anything, but if 100 mg causes stomach bleeds, you are far sicker than you think. Jim