(SLA-011) Analysis of Sex Differences in Potent P2Y12 Inhibitors among Asian Acute Coronary Syndrome (ACS) Patients

Background: Acute Coronary Syndrome (ACS) remains a major cardiovascular disease. East Asian patients receiving DAPT after PCI exhibit lower ischemic risk but higher bleeding risk compared with Caucasians. Consequently, the optimal choice of potent P2Y12 inhibitors for males versus females in East Asian populations remains uncertain.

Objectives: To evaluate the effectiveness and safety profiles of potent P2Y12 inhibitors (ticagrelor and prasugrel), with a specific focus on sex differences in Taiwanese populations.

Methods: This retrospective cohort study examined sex-specific outcomes of Ticagrelor versus Prasugrel in acute coronary syndrome (ACS) patients. Data were derived from the Taiwan National Health Insurance Database between November 1, 2018, and December 31, 2021. The study included ACS patients undergoing PCI with DAPT (aspirin + ticagrelor/prasugrel) and excluded those under 18, with prior ACS, long hospital stays, mixed prescriptions, or CABG.

The primary exposures were ticagrelor and prasugrel, stratified by sex. Key outcomes included major adverse cardiovascular events (MACE) and bleeding events, analyzed to assess the clinical effectiveness and safety of the two treatments. Statistical methods included Cox proportional hazards models for MACE events and sub-distribution hazard models for safety outcomes. Net clinical benefit (NCB) was calculated to balance effectiveness and safety.

Results: A total of 26,745 ACS patients (4,403 women; 22,342 men) were analyzed. Prasugrel users were older than Ticagrelor users, and women receiving Prasugrel had more baseline comorbidities. In men, multivariable regression and propensity-matched analyses showed no significant differences in ischemic or bleeding outcomes between treatments. In women, Prasugrel was associated with ~40% lower risks of 3-point MACE, mortality, and recurrent MI, and propensity-matched analyses suggested reduced BARC 3/5 and gastrointestinal bleeding. However, the small Prasugrel group among women may increase estimation uncertainty. One-year cumulative event rates did not differ significantly between treatment arms. Finally, net clinical benefit analysis (weighting factor 0.8–1.2) increasingly favored low-dose Prasugrel over Ticagrelor in both sexes, indicating that, when balancing ischemic and bleeding risks, low-dose Prasugrel offers greater overall benefit.

Conclusions: In Taiwanese women, low‐dose Prasugrel still significantly reduced the incidence of both ischemic and bleeding events; in Taiwanese men, low‐dose Prasugrel preserved some ischemic protection, but the effect was attenuated and not statistically significant. In net clinical benefit assessments, low‐dose Prasugrel outperformed Ticagrelor overall, especially in women; benefits in men were smaller yet remained consistent and robust. These findings support sex-tailored selection of potent P2Y12 inhibitors to optimize the benefit–risk balance in Taiwanese ACS patients.