The limitations of the Primary Prevention Program (PPP) diabetes substudy have been previously discussed in the original article (1) and in the accompanying editorial (2). Nevertheless, the comments of Dr. de Gaetano (3) require some important additional considerations. 1 ) The results of the substudy are not the outcome of a post hoc analysis, since an oversampling of diabetic patients was planned before the study started to specifically explore the role of aspirin in these patients. 2 ) Dr. de Gaetano suggests that the lower-than-expected effect of aspirin could have also emerged if other subgroups, namely patients with hypertension or hypercholesterolemia, would have been examined. This is not the case—aspirin was effective in reducing the risk for total cardiovascular events in both subgroups …