Sex-stratified differences in early antithrombotic treatment response in patients presenting with ST-segment elevation myocardial infarction

• Published in: The American heart journal Vol. 258; pp. 17 - 26
• Main Authors: Delewi, Ronak, Vogel, Rosanne F., Wilschut, Jeroen M., Lemmert, Miguel E., Diletti, Roberto, van Vliet, Ria, van der Waarden, Nancy W.P.L., Nuis, Rutger-Jan, Paradies, Valeria, Alexopoulos, Dimitrios, Zijlstra, Felix, Montalescot, Gilles, Angiolillo, Dominick J., Krucoff, Mitchell W., Doevendans, Pieter A., Van Mieghem, Nicolas M., Smits, Pieter C., Vlachojannis, Georgios J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2023; Elsevier Limited
• Subjects: Anticoagulants; Antiplatelet therapy; Bleeding; Blood platelets; Cardiovascular disease; Clinical outcomes; Complications; Coronary vessels; Female; Females; Fibrinolytic Agents - therapeutic use; Gender differences; Glycoproteins; Heart attacks; Hemorrhage - chemically induced; Hemorrhage - epidemiology; Hospitals; Humans; Male; Males; Medical imaging; Myocardial infarction; Patients; Percutaneous Coronary Intervention - adverse effects; Pharmacodynamics; Platelet Aggregation Inhibitors - adverse effects; Platelets; Prasugrel Hydrochloride - therapeutic use; Reactivity; Regression analysis; Segments; Sex; Sex differences; Sexes; ST Elevation Myocardial Infarction - therapy; Treatment Outcome; Spain
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2022.12.013

The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P = .04). In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation.