Pivotal randomized clinical trials (RCTs) conducted in the 1970s and 1980s comparing aspirin with placebo in patients with prior myocardial infarction established antithrombotic agents as mainstays for the prevention of cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). Since then, other oral antithrombotic agents of different classes – including P2Y12 inhibitors, protease-activated receptor-1 inhibitors, and direct oral anticoagulants (DOACs) – have been developed and tested, alone or in various combinations, in this patient population.