Low-dose aspirin benefit shown in stable CVD patients

Low-dose aspirin benefit shown in stable CVD patients

By Caroline Price

09 January 2008

Am J Med 2008; 121: 43-49

MedWire News: Low-dose aspirin is associated with a significant reduction in the risk for major cardiovascular events and all-cause mortality, and a significant increase in the risk for major bleeding in patients with stable cardiovascular disease (CVD), meta-analysis findings show.

Despite the increased bleeding risk, "the totality of evidence demonstrated the benefit of aspirin in this high-risk group of subjects," comment the authors.

Recommendations for aspirin in secondary prevention are based on analyses of all anti-platelet therapies at all doses and in both stable and unstable patients, such that the role of low-dose aspirin in stable patients remains poorly defined, explain Jeffrey Berger (Duke University, Durham, North Carolina) and colleagues.

To address this issue, the team searched the MEDLINE database for secondary prevention trials of low-dose aspirin in stable CVD patients published between 1966 and 2006.

They identified six randomized placebo-controlled trials, one (Cardiff-I) that enrolled patients with a prior myocardial infarction (MI), one (Swedish Angina Pectoris Asprin Trial) that included patients with chronic stable angina, and four (Danish Low Dose, UK Transient Ischemic Attack, Swedish Aspirin Low-Dose Trial, and European Stroke Prevention Study-2) that included patients with a prior stroke or transient ischemic attack.

The aspirin dose ranged from 50 to 300 mg daily. Overall, there were 1718 cardiovascular events (nonfatal MIs, nonfatal strokes, and cardiovascular deaths) in these studies during a mean follow-up of 33.3 months.

There were significantly fewer cardiovascular deaths among patients taking aspirin (15.8%) than those taking placebo (19.1%), representing a 21% reduction in the odds for cardiovascular events with aspirin use (p<0.01).

Aspirin therapy was also associated with a 13% reduction in the odds for all-cause mortality (p=0.03), a 26% reduction in the odds for nonfatal MI (p<0.01), and a 25% reduction in the odds for stroke (p<0.01).

Against these findings, patients who received aspirin had a more than two-fold increased risk for major bleeding. However, the authors note that the low absolute risk for major bleeding meant that the number needed to treat to cause a major bleed was 111.

Furthermore, the data indicated that treating 1000 patients with low-dose aspirin would prevent around 33 major cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, while causing just nine major bleeds, the researchers report in the American Journal of Medicine.

Of note, the decreased risk for major cardiovascular events was driven primarily by a reduction in the risk for MI in the two trials including patients with ischemic heart disease, and primarily by a reduction in the risk for stroke in the four trials that enrolled patients who had suffered cerebrovascular events.

Sub-group analyses showed that the effects of aspirin were similar at doses of 50-100 mg/day and 300 mg/day.

Berger and team conclude: "Future studies should focus on proper patient selection and management options to reduce the bleeding risk and the most optimal aspirin dose in each clinical setting for the long-term reduction in CVD and mortality."

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