Assessing the risk/benefit profile before recommending aspirin for the primary prevention of cardiovascular events.

Department of Epidemiology and Biostatistics and the Division of General Internal Medicine, University of California, San Francisco
The American Journal of Medicine (Impact Factor: 5.3). 11/2004; 117(7):528-30. DOI: 10.1016/j.amjmed.2004.07.037
Source: PubMed
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    ABSTRACT: Randomized trials have shown that low-dose aspirin decreases the risk of a first myocardial infarction in men, with little effect on the risk of ischemic stroke. There are few similar data in women. We randomly assigned 39,876 initially healthy women 45 years of age or older to receive 100 mg of aspirin on alternate days or placebo and then monitored them for 10 years for a first major cardiovascular event (i.e., nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes). During follow-up, 477 major cardiovascular events were confirmed in the aspirin group, as compared with 522 in the placebo group, for a nonsignificant reduction in risk with aspirin of 9 percent (relative risk, 0.91; 95 percent confidence interval, 0.80 to 1.03; P=0.13). With regard to individual end points, there was a 17 percent reduction in the risk of stroke in the aspirin group, as compared with the placebo group (relative risk, 0.83; 95 percent confidence interval, 0.69 to 0.99; P=0.04), owing to a 24 percent reduction in the risk of ischemic stroke (relative risk, 0.76; 95 percent confidence interval, 0.63 to 0.93; P=0.009) and a nonsignificant increase in the risk of hemorrhagic stroke (relative risk, 1.24; 95 percent confidence interval, 0.82 to 1.87; P=0.31). As compared with placebo, aspirin had no significant effect on the risk of fatal or nonfatal myocardial infarction (relative risk, 1.02; 95 percent confidence interval, 0.84 to 1.25; P=0.83) or death from cardiovascular causes (relative risk, 0.95; 95 percent confidence interval, 0.74 to 1.22; P=0.68). Gastrointestinal bleeding requiring transfusion was more frequent in the aspirin group than in the placebo group (relative risk, 1.40; 95 percent confidence interval, 1.07 to 1.83; P=0.02). Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older. In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point.
    New England Journal of Medicine 04/2005; 352(13):1293-304. · 54.42 Impact Factor
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    ABSTRACT: The assumption that disease specific risk factors are similar or the same in men and women may lead to incorrect primary prevention strategies. This study focused on the evaluation of gender-specific Alzheimer's disease (AD) risk factors. In AD, female gender appears to be an important risk factor associated with the aberrant production of beta amyloid (βA) peptides. Although decreased levels in plasma DHA concentration are associated with cognitive decline in healthy elderly and Alzheimer's patients, pre-treatment with DHA significantly reduced the survival of cortical neurons incubated with beta amyloid (βA). Hence, in the presence of an increasing amount of βA, paradoxically women - who have higher plasma levels of DHA - are more likely to develop AD. Aspirin (ASA) converts cyclooxygenase (COX)-2 into a form that generates new neuroprotective docosanoids from DHA; therefore, ASA might positively resolve the paradoxical effect of the concomitant presence of DHA and βA.
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    ABSTRACT: There is consensus that a more transparent, explicit, and rigorous approach to benefit-risk evaluation is required. The objective of this study is to evaluate the incremental net benefit (INB) framework for undertaking quantitative benefit-risk assessment by performing a quantitative benefit-risk analysis of alosetron for the treatment of irritable bowel syndrome from the patients' perspective. A discrete event simulation model was developed to determine the INB of alosetron relative to placebo, calculated as "relative value-adjusted life-years (RVALYs)." In the base case analysis, alosetron resulted in a mean INB of 34.1 RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Incorporating parameter uncertainty into the model, probabilistic sensitivity analysis revealed a mean INB of 30.4 (95% confidence interval 15.9-45.4) RVALYs per 1000 patients treated relative to placebo over 52 weeks of treatment. Overall, there was >99% chance that both the incremental benefit and incremental risk associated with alosetron are greater than placebo. As hypothesized, the INB of alosetron was greatest in patients with the worst quality of life experienced at baseline. The mean INB associated with alosetron in patients with mild, moderate, and severe symptoms at baseline was 17.97 (-0.55 to 36.23), 29.98 (17.05-43.37), and 35.98 (23.49-48.77) RVALYs per 1000 patients treated, respectively. This study demonstrates the potential utility of applying the INB framework to real-life decision-making, and the ability to use simulation modeling incorporating outcomes data from different sources as a benefit-risk decision aid.
    Value in Health 09/2009; 13(4):411-7. · 2.89 Impact Factor