Aspirin and antioxidants are not effective in primary prevention of cardiovascular events in patients with diabetes and asymptomatic peripheral arterial disease, according to a Scottish clinical trial published online in BMJ.
In a multiarm interventional study, researchers in the multicenter prevention of progression of arterial disease and diabetes trial found that subjects in the two arms taking aspirin and in the two arms taking antioxidants did not experience significantly fewer myocardial infarctions, strokes, or other cardiovascular events than did subjects in placebo arms.
Aspirin in particular carries with it risks of gastrointestinal bleeding and other adverse events, so physicians may want to avoid prescribing it for primary prevention, given that it does not seem to be effective in the population studied.
“Although the calculated risk of major bleeding is relatively small, the number of people taking aspirin is relatively large, and therefore in population terms, aspirin-induced bleeding is a major problem,” said Dr. Jill Belch of the Institute of Cardiovascular Research at the University of Dundee (Scotland) and her associates. “Aspirin should, however, still be given for secondary prevention of cardiovascular disease in people with diabetes mellitus, when the evidence base is convincing, and the results of this study must not detract from this important standard of care.”
The researchers randomized 1,276 patients aged 40 years or older at 16 hospitals in Scotland. The patients had type 1 or 2 diabetes and asymptomatic peripheral artery disease; they were randomized into groups taking aspirin and antioxidants, aspirin plus a placebo, antioxidants plus a placebo, or two placebos.
The aspirin groups took 100 mg daily and the antioxidant groups took a capsule of 200 mg alpha-tocopherol, 100 mg ascorbic acid, 25 mg pyridoxine, 10 mg zinc, 10 mg nicotinamide, 9.4 mg lecithin, and 0.8 mg selenite, according to researchers. Patients were followed up every 6 months for a median of 6.7 years, for a total of 8,127 patient-years of follow-up, according to the researchers (BMJ 2008 Oct. 17 [doi:10.1136/bmj.a1840]).
The researchers selected a composite end point of death from coronary heart disease or stroke, nonfatal myocardial infarction or stroke, or above-ankle amputation for critical limb ischemia.
In the two aspirin groups, 18.2% (116 of 638) experienced one of the composite end point events, compared with 18.3% (117 of 638) in the no-aspirin groups, a nonsignificant difference. In the two antioxidant groups, 18.3% (117 of 640) experienced one of those events, compared with 18.2% (116 of 636) in the no-antioxidant groups, also a nonsignificant difference, the researchers said.
They added that one reason aspirin may have been ineffective in primary prevention is the emergence of statin therapy in the diabetic population, which was allowed as standard therapy at the discretion of investigators and other clinicians. At two of the participating centers, researchers have found a drop-off in the mean total cholesterol level of 6 mmol/L in 1996 to 4.3 mmol/L in 2007 in a total of 10,000 diabetic patients. They added that future research should consider whether aspirin provides benefit in addition to that of statins.
“Studies evaluating the possible benefits of aspirin for primary prevention in patients without cardiovascular disease have been consistently negative,” commented Dr. William R. Hiatt of the University of Colorado at Denver in an accompanying editorial (BMJ 2008 Oct. 17 [doi:10.1136/bmj.a1806]).
“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 researchers disclosed no conflicts of interest.
Dr. Hiatt reported having served on the Food and Drug Administration's cardiovascular and renal drugs advisory committee, which reviewed aspirin in 2003.