Comparison of short-term clinical outcomes between low-dose prasugrel and clopidogrel as part of triple antithrombotic therapy in patients requiring oral anticoagulant therapy and percutaneous coronary intervention

BACKGROUND: Triple antithrombotic therapy, including dual antiplatelet therapy and oral anticoagulant (OAC), is recommended for a short-term period after percutaneous coronary intervention (PCI) in patients requiring anticoagulation therapy. The purpose of this study was to compare in-hospital clinical outcomes between low-dose prasugrel (3.75 mg/day) and clopidogrel, as part of triple antithrombotic therapy, using a large database in Japan. METHODS: Patients with ischemic heart disease who underwent PCI between January 2015 and December 2019, and were prescribed triple therapy with aspirin, a P2Y12 inhibitor (clopidogrel or low-dose prasugrel), and OAC (direct oral anticoagulant: DOAC or vitamin K antagonist: VKA), were selected from the Diagnosis Procedure Combination database. The primary outcome was in-hospital mortality. The secondary outcomes were myocardial infarction, ischemic stroke, bleeding stroke, gastrointestinal bleeding, and blood transfusion. RESULTS: Overall, 5,777 patients were eligible in this analysis. The patients were divided into 4 subgroups according to the type of P2Y12 inhibitor and OAC: clopidogrel/DOAC (n = 1,628), clopidogrel/VKA (n = 1,334), prasugrel/DOAC (n = 1,607), and prasugrel/VKA (n = 1,208). There was no significant difference in the incidence of death and gastrointestinal bleeding among the 4 subgroups. The prasugrel/DOAC group had significantly lower incidence of MI (OR 0.566, 95% CI 0.348-0.921). The incidence of ischemic stroke was significantly lower in the prasugrel/DOAC group (OR 0.701, 95% CI 0.502-0.979), and significantly higher in the clopidogrel/VKA group (OR 1.680, 95% CI 1.273-2.216). Need for blood transfusion was less frequent in the prasugrel/DOAC group (OR 0.729, 95% CI 0.598-0.890), and more frequent in both the clopidogrel/VKA group (OR 1.424, 95% CI 1.187-1.708) and the prasugrel/VKA group (OR 1.633, 95% CI 1.367-1.950). CONCLUSIONS: Combination of low-dose prasugrel and DOAC was associated with lower incidence of MI, ischemic stroke, and blood transfusion. Low-dose prasugrel may be feasible as part of triple therapy in patients undergoing PCI.