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Aspirin Use Particularly Beneficial for Older Patients and Those With Impaired Exercise Capacity or a History of Coronary Artery Disease
September 9, 2001 — Among patients being evaluated for known or suspected heart disease, aspirin use is associated with a reduced long-term risk of death from all causes, according to an article in the September 12 issue of The Journal of the American Medical Association.
Patricia A. Gum, M.D., Michael S. Lauer, M.D., and colleagues from the Cleveland Clinic Foundation in Cleveland, conducted a study to determine if aspirin use is associated with a reduction in all-cause mortality among stable patients referred for stress echocardiography, and to identify patient characteristics that predict the maximum absolute mortality benefit from aspirin. Echocardiography is a diagnostic test that uses ultrasound to make images of the heart chambers, valves and surrounding structures to detect abnormalities. A stress echocardiogram is performed after a period of physical exertion.
According to background information cited in the article, aspirin has been shown to reduce risk from cardiovascular disease and short-term mortality following a heart attack. But the association between its use and long-term all-cause mortality has not been well defined.
The authors followed 6,174 patients who underwent stress echocardiography at the Cleveland Clinic Foundation from 1990 to 1998. The patients included 2,310 (37 percent) who were taking aspirin. Patients were excluded if they had significant disease of the heart valves or a documented reason that they should not use aspirin — including ulcers, kidney failure and use of non-steroidal anti-inflammatory drugs. During 3.1 years of follow-up, 276 patients (4.5 percent) died.
"Among consecutive patients referred for stress echocardiography to evaluate known or suspected coronary artery disease, aspirin use was associated with a substantial reduction of all-cause mortality," the authors write.
Because use of aspirin or no use of aspirin was not assigned randomly, the authors performed a statistical analysis (a propensity score) that summarizes the likelihood for a patient with any given set of characteristics to receive aspirin. They performed an analysis on pairs of patients — one using aspirin and the other not using aspirin — with both members of the pair having the same aspirin-use propensity score.
"In further analysis using matching by propensity score, 1,351 patients who were taking aspirin were at lower risk for death than 1,351 patients not using aspirin [4 percent vs. 8 percent, respectively; 47 percent lower risk with aspirin use]," the authors report. "After adjusting for the propensity for using aspirin, as well as other possible confounders and interactions, aspirin use remained associated with a lower risk for death [44 percent lower risk with aspirin use]."
The authors estimated the absolute benefit of aspirin based on specific patient characteristics, to predict which patients might benefit most from aspirin treatment. "We showed aspirin to be particularly beneficial among patients who were older, who had impaired exercise capacity, or who had a history of coronary artery disease," they write.
The authors acknowledge the major limitation of their study was that aspirin use was not based on randomized assignment. "Despite these limitations, the association between aspirin use and reduced mortality meets currently accepted criteria for likely causality. The association was strong, with a greater than 30 percent reduction in risk of death," they write.
"Thus, our findings provide additional support for recommending the routine use of aspirin in patients with, or at risk for, cardiovascular disease — not only for preventing morbid events but also for reducing all-cause mortality," they conclude.
Editor's Note: Co-authors Michael S. Lauer, M.D., and Eugene H. Blackstone, M.D., receive grant support from the American Heart Association and from the National Heart, Lung and Blood Institute. None of the investigators own stock, equity or receive any form of remuneration from any pharmaceutical or medical device company.
Editorial: Using Observational Studies To Expand the Evidence Base for Therapy
In an accompanying editorial, Martha J. Radford, M.D., and JoAnne M. Foody, M.D., of Yale University School of Medicine in New Haven, Conn., and Qualidigm in Middletown, Conn., point to the study by Gum et al as an example of how results of these types of studies may be applied to a broader population.
"Sophisticated observational studies such as that of Gum et al provide assurance that extending the results of the randomized trials of aspirin to unstudied or understudied patient groups, in this case those with suspected coronary artery disease who have impaired exercise capacity, will provide benefit rather than harm," they write.
"Insightful scrutiny of patterns and outcomes of care in population-based cohorts, informed by insights from basic science research and the results of randomized clinical trials, assures physicians about risks and benefits of therapies for patients not enrolled in trials and helps to guarantee that as many patients as possible are considered for effective therapies," they conclude.