Effectiveness and Safety of Reduced-Dose Prasugrel in an East Asian Population: PRASFIT-ACS Emulation Using National Health Insurance Claims Data.

Abstract

Prasugrel is recommended for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, East Asians exhibit a stronger antiplatelet response, raising concerns about bleeding risks with standard dosing. This retrospective cohort study evaluated the real-world effectiveness and safety of reduced-dose prasugrel in an East Asian population by emulating the pivotal PRASFIT-ACS trial using Taiwan's National Health Insurance claims data. In this study, ACS patients were classified into reduced-dose prasugrel or clopidogrel groups post-PCI. We estimated the intention-to-treat effect of initiating reduced-dose prasugrel vs. clopidogrel on the risk of major adverse cardiovascular events (MACE) and the per-protocol effect of treating with reduced-dose prasugrel on major bleeding risk using Cox proportional hazard models. A total of 4833 ACS patients were analyzed, including 977 (20.2%) who received reduced-dose prasugrel. Reduced-dose prasugrel showed comparable effectiveness to clopidogrel in preventing MACE (HR: 0.96, 95% CI: 0.72-1.29) and did not increase bleeding risk (HR: 0.82, 95% CI: 0.36-1.90), consistent with PRASFIT-ACS results (HR_MACE: 0.85, 95% CI: 0.62-1.16; HR_Bleeding: 0.82, 95% CI: 0.39-1.73). A significant reduction in cardiovascular mortality was observed (HR: 0.51, 95% CI: 0.29-0.89), differing from PRASFIT-ACS findings (HR: 1.21, 95% CI: 0.48-3.06). Our results suggest that reduced-dose prasugrel was effective in preventing thrombotic events in the Taiwanese population without significantly increasing bleeding risk. These findings align with pivotal trial outcomes while highlighting the importance of race-specific dose adjustments to optimize ACS treatment strategies. Further research is needed to evaluate whether these results are applicable to other East Asian populations.