Intensified Antiplatelet Therapy in Post-PCI Patients With High On-treatment Platelet Reactivity: the OPTIMA-2 Trial

OPTImal Management of Antithrombotic agents: OPTIMA-2 trial

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the foundation antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI). Clopidogrel is the most commonly used P2Y12 receptor inhibitor worldwide because it is effective and inexpensive1. High on-treatment platelet reactivity (HOPR) occurs in as many as one-third of patients treated with standard dose clopidogrel (75mg once daily), and is associated with an increased risk of major adverse cardiovascular events (MACE).

Various approaches have been tested to overcome HOPR in patients treated with aspirin and clopidogrel, including higher doses of clopidogrel; the addition of cilostazol; and replacement of clopidogrel with prasugrel; however, the results of these intensified treatments were controversial, and a more potent P2Y12 receptor inhibitor, ticagrelor has never been studied in this scenario.

TOPIC study showed that short-term (i.e. 1-month) intensification of antiplatelet treatment might be sufficient to achieve optimal outcomes. Similarly, TROPICAL ACS showed that guided de-escalation of antiplatelet treatment with clopidogrel was non-inferior to the treatment with prasugrel at 1 year after PCI in terms of net clinical benefit, which suggests that routinely long-term intensification of antiplatelet treatment is not required for all PCI patients.

Accordingly we performed a randomized trial to test the hypothesis that in patients with HOPR intensification of antiplatelet therapy with double dose clopidogrel, the addition of cilostazol, or replacement of clopidogrel with ticagrelor for 1 month followed by resumption of conventional DAPT with aspirin and clopidogrel for 11 months would be superior to conventional DAPT for 12 months in reducing the prevalence of HOPR and MACE without increasing bleeding.