Triple versus Dual Antiplatelet Therapy in Acute Coronary Syndromes: Adding Cilostazol to Aspirin and Clopidogrel?

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is the standard of care in acute coronary syndromes. Additionally, novel P2Y12 receptor antagonists such as prasugrel and ticagrelor are even recommended over clopidogrel in certain clinical guidelines. Despite the fact that clopidogrel is fraught with significant variability in on-treatment platelet reactivity, the novel P2Y12 receptor antagonists come at the price of increased side effects and cost. Therefore, alternative or supplementary antiplatelet therapies are needed. Cilostazol, a phosphodiesterase III inhibitor, has been shown to significantly improve high on-treatment platelet reactivity in patients receiving both aspirin and clopidogrel and has antiproliferative effects (inhibiting neointimal hyperplasia and smooth muscle proliferation), thus reducing the risk of restenosis after coronary stent implantation. Further, cilostazol in addition to aspirin and clopidogrel versus DAPT in patients undergoing percutaneous coronary intervention showed that triple antiplatelet therapy (TAPT) was associated with a significantly greater platelet inhibition, reduced major adverse cardiovascular events, target lesion revascularization, and target vessel revascularization with no increased risk for a hemorrhagic event. Moving forward, larger randomized controlled trials are required comparing TAPT versus DAPT (clopidogrel, prasugrel or ticagrelor on top of aspirin).