American Journal of Epidemiology Vol. 155, No. 11 : 1045-1053
Copyright © 2002 by The Johns Hopkins University School of Hygiene and Public Health
ORIGINAL CONTRIBUTIONS |
Use of a Marginal Structural Model to Determine the Effect of Aspirin on Cardiovascular Mortality in the Physicians' Health Study
1 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
3 Department of Medicine, Epidemiology and Public Health, University of Miami School of Medicine, Miami, FL.
The 1982–1988 aspirin component of the Physicians' Health Study, a randomized trial of aspirin and ß-carotene in primary prevention of cardiovascular disease and cancer among 22,071 US male physicians, was terminated early primarily because of a statistically extreme 44% reduction in first myocardial infarction, with inadequate precision and no apparent effect on the primary endpoint, cardiovascular death. Because of the demonstrated efficacy of aspirin in secondary prevention of cardiovascular death, nonfatal cardiovascular events may simultaneously be time-dependent confounders and intermediate variables. Aspirin use is strongly influenced by these as well as other diseases, side effects, and cardiovascular risk factors. The authors used a marginal structural model with time-dependent inverse probability weights to estimate the underlying causal effect of aspirin on cardiovascular mortality. Although intention-to-treat analyses found no effect (rate ratio = 1.00, 95% confidence interval (CI): 0.72, 1.38), the estimated causal rate ratio was altered to 0.75 but remained nonsignificant (95% CI: 0.48, 1.16). As-treated analyses suggested a more modest effect of aspirin use (rate ratio = 0.90, 95% CI: 0.65, 1.25). Although the numbers of cardiovascular deaths were insufficient to evaluate this endpoint definitively, use of such methods holds much potential for controlling time-varying confounders affected by previous exposure.
aspirin; bias (epidemiology); cardiovascular diseases; confounding factors (epidemiology); epidemiologic methods; mortality; myocardial infarction
Abbreviations: CABG, coronary artery bypass graft; CI, confidence interval; MI, myocardial infarction; PTCA, percutaneous transluminal coronary angioplasty; RR, rate ratio
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