In theory, there are several possible alternative explanations for the observed findings, namely, chance, bias, and confounding.30 Chance seems unlikely, as the principal findings are highly statistically significant and derived from 2 large-scale trials that randomized and observed 13 173 patients for 5 to 6 years and from meta-analyses with more than 73 900 patient-years of observation. Bias also seems unlikely, because the data are prospective and there were virtually no losses to follow-up. Furthermore, the possibility of bias is lessened by the uniformly high and equal rates of aspirin use in the pravastatin and placebo groups. Despite the fact that all the trials were randomized for pravastatin use, residual confounding is plausible because the analyses were observational for aspirin use. Several factors, however, render this possibility less likely. First, we controlled for a large number of potential confounding variables. Second, the results were consistent in the analyses of the individual trials and in meta-analyses using 3 different assumptions. Third, the aspirin results were consistent with the most recent findings in the Antithrombotic Trialists' Collaboration, which included 287 randomized trials of secondary prevention, most with aspirin, involving more than 135 000 patients.12 Fourth, while aspirin use was defined at baseline, 97% of patients were still taking the drug at the end of the trials. Furthermore, the likely effect, if any, of drop-ins would be to dilute the magnitude of observed effects. Fifth, while information was not available on dosage, it is clear from the Antithrombotic Trialists' Collaboration that the cardiovascular benefits of aspirin are virtually identical across a wide range of daily dosages, from 75 mg to higher than 1800 mg.11,12 Despite these and perhaps other limitations, we believe these analyses represent the best evidence on the question of the additive benefits of pravastatin and aspirin on CVD. We further believe that the most plausible interpretation of the findings is that the combination of pravastatin and aspirin is superior to either agent alone, each of which confers statistically significant and clinically important benefits in the secondary prevention of CVD.