In patients with peripheral artery disease (PAD), aspirin use is associated with a statistically non-significant decrease in the combined risk of nonfatal MI, nonfatal stroke and cardiovascular (CV) death, but a significant reduction in the risk of nonfatal stroke, according to a meta-analysis in the May 13 issue of Journal of the American Medical Association.
Jeffrey S. Berger, MD, of the University of Pennsylvania in Philadelphia, and colleagues wrote that aspirin's effectiveness in patients with PAD remain uncertain, and that the study's findings may be limited by the lack of a large study population. Despite limited supporting data, some current guidelines recommend aspirin use for patients with PAD.
To assess the effect of aspirin on CV event rates in patients with PAD, Berger and colleagues conducted a meta-analysis to evaluate evidence from randomized controlled trials of aspirin therapy, with or without the antiplatelet agent dipyridamole, that reported CV event rates (the primary events for this analysis were nonfatal MI, nonfatal stroke and CV death).
The researchers identified 18 trials, which included 5,269 patients, of whom 2,823 were randomized to aspirin therapy (of these, 1,516 received aspirin monotherapy) and 2,446 were randomized to placebo or control.
The investigators found that a total of 8.9 percent of CV events in patients receiving any aspirin therapy, compared with 11 percent of events among the control patients--a 12 percent reduction in CV event rates, which was not statistically significant. Results for associations of aspirin therapy with the individual components of the primary events indicated that the risk of nonfatal stroke was significantly lower (34 percent) in the aspirin group than in the placebo (a rate of events of 1.8 vs. 3.1 percent), but was not associated with significant reductions in all-cause or CV death, MI or major bleeding.
A total of 125 CV events occurred among 8.2 percent of patients receiving aspirin monotherapy, compared with 144 events among 9.6 percent of patients in the placebo or control groups, the researchers said. Aspirin monotherapy was associated with a 36 percent reduction in the risk of nonfatal stroke (2.1 vs. 3.4 percent), but no statistically significant reductions in all-cause or CV death, MI or major bleeding.
"Results of this meta-analysis demonstrated that for patients with PAD, aspirin therapy alone or in combination with dipyridamole did not significantly decrease the primary end point of cardiovascular events, results that may reflect limited statistical power," the authors wrote. "The major limitations of this meta-analysis reflect the limitations of published literature on aspirin for treating PAD. Many of these trials were small and of short duration, resulting in few major cardiovascular events."
In the accompanying editorial, Mary McGrae McDermott, MD, of the Northwestern University Feinberg School of Medicine in Chicago, and Michael H. Criqui, MD, of the University of California, San Diego School of Medicine, said that more research is needed regarding the outcomes of aspirin use by patients with PAD.
"The meta-analysis by Berger et al enriches current understanding of the association of aspirin with cardiovascular outcomes in patients with PAD. However, based on the limitations of data available, the findings should not alter recommendations for aspirin as an important therapeutic tool for secondary prevention in patients with PAD," they wrote. "To best inform evidence-based clinical practice guidelines, more high-quality clinical trials are needed. Achieving this will require greater resources for research and a larger critical mass of clinical investigators dedicated to the study of PAD.
"However the current evidence was insufficient to rule out small yet important benefits of aspirin (as suggested by the point estimate of a 12 percent risk reduction)," they added. "Larger prospective studies of aspirin and other antiplatelet agents are warranted among patients with PAD in order to draw firm conclusions about clinical benefit and risks."