Aspirin Resistance in Diabetic Patients : Response to Sacco et al.

The results in the small diabetic subgroup of the Primary Prevention Project (PPP) study (744 patients), implemented by 287 additional patients (enrolled in outpatient clinics) were recently published in Diabetes Care (1). The PPP trial (2) was originally designed to test the hypothesis that platelet thromboxane (TxA2) generation would act as an intermediate “common” mechanism of cardiovascular risk in addition to specific risk factors (namely old age, hypertension, hypercholesterolemia, diabetes, obesity, and family history of myocardial infarction). The results of the original PPP trial extended the indications for aspirin treatment beyond secondary prevention in men and women with major cardiovascular risk factors, as routinely seen in a unique scenario such as general practice. As there was no obvious excess risk for hemorrhagic cerebrovascular complications, the results of the PPP trial not only widened the categories of candidates to a low-cost prophylaxis but also offered clear support to a crucial pathogenic role of platelet TxA2 in the final steps of the atherosclerotic process (3). Sacco et al. (1) now suggest that diabetic patients are less responsive to aspirin therapy than other high-risk individuals enrolled in the PPP trial. It was not shown, however, whether aspirin would have in contrast been effective if other similarly small subgroups of people at risk would have been compared with the rest of the selected population. This is of importance, as it has been previously reported that aspirin may be less effective in subjects with hypertension (4) or hypercholesterolemia (4–6). On one hand, a significantly higher percentage of subjects with hypertension and hypercholesterolemia were present in the diabetic group randomized to aspirin, compared with the no-aspirin group (1); this could have further contributed to the negative results. On the other hand, it appears somewhat contradictory to state that a clear benefit of aspirin could only be shown in the heterogeneous group of nondiabetic patients, which included 68.8% hypertensive and 39.9% hypercholesterolemic subjects (1). It therefore appears premature to raise the fashionable issue of “aspirin resistance” (7,8) in diabetic patients (1) until adequately sized, statistically powered clinical trials and/or large meta-analyses can match the efficacy and safety of aspirin in primary prevention in different subgroups of patients with different vascular risk profiles, rather than in small groups of diabetic patients.