Post-discharge bleeding after an acute coronary syndrome among patients with advanced age treated with different dual antiplatelet therapy regimens: a report of 16,653 patients from two real-world multinational registries

Introduction and objectives: ticagrelor compared to clopidogrel is feared to cause more bleedings in acute coronary syndrome (ACS) patients, especially in the elderly. We sought to assess the incidence of major bleedings (MB), reinfarction (REAMI) and death to overall causes in old patients in order to evaluate the safety and efficacy of ticagrelor versus clopidogrel in a population considered at high risk. Methods: we collected data by merging together the RENAMI and the BleeMACS, two real-world registries that enrolled patients discharged with a definitive diagnosis of ACS who underwent percutaneous coronary intervention (PCI) and treated with dual antiplatelet therapy (DAPT). We excluded patients treated with prasugrel and/or oral anticoagulants (OAC). Primary end points were MB, REAMI and death to all causes at one year follow-up (FU). Results: a total of 16.653 patients (13153 patients <75 y.o, 3500 patients >75 y.o, 1717 patients >80 y.o) were included. Ticagrelor was significantly underutilized (<75 y.o 20.8%, >75 y.o 16.3%, >80 13.9% y.o p<0.001). The Kaplan-Meier curves did not show ticagrelor to increase the incidence of MB irrespectively of age compared to clopidogrel (log-rank=0.13), while reducing the incidence of REAMI and death to all causes in patients >75 y.o and >80 y.o (log-rank=0.001). After propensity score matching (PSM), 3500 patients <75 and >75 y.o were selected. Ticagrelor was underutilized (<75 y.o 16.5%, >75 16.3% y.o p=0.821, >80 13.9 y.o p<0.001). Results were comparable for MB (75 y.o group log-rank=0.787, 80 y.o group log-rank=0.872), REAMI (75 y.o group log-rank=0.001, 80 y.o group log-rank=0.001) and death to all causes (75 y.o group log-rank=0.001, 80 y.o group log-rank=0.001). At multiple Cox regression analysis age, creatinine >1.5 mg/dl, femoral access and prior bleeding, but not DAPT with ticagrelor, resulted as independent predictor of bleeding. Conclusions: considering these two real-world registries, ticagrelor did not increase MB compared to clopidogrel in ACS patients, while reducing the incidence of REAMI and death to overall causes in the elderly. Age does not seem to represent a contraindication per se to the use of ticagrelor favouring clopidogrel in order to reduce MB.