Several large trials have evaluated the efficacy and safety of more intensive antiplatelet strategies for long-term prevention of major adverse cardiovascular events (MACE; typically cardiovascular death, myocardial infarction [MI], or stroke). While professional societies have evaluated the primary findings of these trials in practice guidelines, additional analyses have provided further insight into the benefit and risk in specific populations.

Patients with prior MI are at a higher risk of MACE than patients who have coronary disease and no history of MI. Accordingly, data from several trials demonstrate greater benefit of more intensive long-term antiplatelet therapy in such patients. In the Clopidogrel and Aspirin Versus Aspirin Alone for the Prevention of Atherothrombotic Events trial (CHARISMA), which was neutral overall, patients with prior MI had a 23% relative risk reduction in MACE with the addition of clopidogrel to aspirin, in contrast to those without clinically evident vascular disease in whom there was a trend toward harm. In the Dual Antiplatelet Therapy trial,¹ the subgroup of patients with a prior MI derived a larger ischemic benefit from prolonged P2Y₁₂ inhibition (44% vs 17% relative risk reduction). In addition, while the excess in noncardiovascular mortality observed in the DAPT trial overall continues to generate debate, it appeared to be confined to the group without prior MI.