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

Abstract

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).

Efficacy and Safety of Novel Oral P2Y12 Receptor Inhibitors in Patients With ST-Segment Elevation Myocardial Infarction Undergoing PCI: A Systematic Review and Meta-Analysis

“…A total of 17 potentially eligible studies were reviewed and detailed evaluations were made. Among these, 5 trials were excluded because it was found that they did not meet the inclusion criteria after the full-texts were read (2 compared DAPT with triple antiplatelet therapy 18 , 19 ; 1 trial had an inconsistent outcome 20 ; and 2 trials were non-STEMI studies). 21 , 22 Finally, 12 RCTs 6 , 10 , 23 – 32 were included in the final meta-analysis.…”

Efficacy and safety of vorapaxar for the prevention of adverse cardiac events in patients with coronary artery disease: a meta-analysis

“…In the standard dual anti-platelet therapy of patients with CAD, aspirin and thienopyridine are recommended to be used in combination (14)(15)(16). Aspirin is an irreversible inhibitor of cyclooxygenase-1 that produces a permanent defect in thromboxane A2-mediated platelet activation (17), while thienopyridine prevents adenosine diphosphateinduced platelet activation and aggregation by irreversibly inhibiting the P2Y12 receptor (17,18).…”

Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications

“…Hence, in certain high-risk patients, one may opt for such an antiplatelet approach, once the benefits or equivalency are further established via direct comparative studies with the newer antiplatelet agents. 290 Until then, cilostazol has its niche in certain patient groups, including patients with PAD in decreasing symptoms and protecting patients after angioplasty and stenting, patients with CAD undergoing PCI in decreasing restenosis and enhancing DAPT, and in patients with stroke for secondary prevention and mitigating restenosis after carotid stenting, without increasing bleeding complications. Further comparative RCTs may provide additional robust evidence for expanding cilostazol's current indications and establishing these potential new indications, as detailed in this review.…”