Women are at a greater risk than men of having a major or life-threatening bleeding when receiving aspirin before and after a transcatheter aortic valve replacement (TAVR) is performed, a post hoc analysis concludes. In new findings, scientists suggest most of the bleeding events, which occurred at the access site, may be due to women having smaller and more tortuous arteries, leading to more vascular complications and, thus, bleeding. The research team put forward a case for a sex-specific approach to antithrombotic management prior to and after TAVR depending on whether an oral anticoagulant (OAC) is necessary. “To our knowledge, this is the first study to show a possible interaction between aspirin and sex-specific major or life-threatening bleeding after TAVR,” said the research team, writing in the May 8 issue of JACC Cardiovascular Interventions, which was also published Monday online. “Women may have beneficial effects with other regimens, like P2Y12 inhibitors,” the team added, citing one notable study showing a reduction in bleeding risks in P2Y12 inhibitors vs. aspirin after PCI. Details of the POPular TAVI trial Researchers co-led by Kees H. van Bergeijk, MD, from the University of Groningen in the Netherlands, carried out a post hoc analysis on patient data from the Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation (POPular TAVI) trial. Here, 978 patients (48% female) were included in the investigator-initiated, parallel-group, randomized open-label trial carried out across 17 sites in Europe. The study consisted of two cohorts, where cohort A consisted of patients without an OAC indication randomized between aspirin with or without clopidogrel for 3 months after TAVR in a 1:1 ratio. In this cohort, patients on maintenance antiplatelet therapy were advised to continue aspirin (or aspirin and clopidogrel in case of a recent PCI within the previous 3 months). Patients on maintenance aspirin received a 300-mg loading dose of clopidogrel the day before TAVR or on the day of TAVR. Aspirin-naïve patients received a loading dose of aspirin the day before TAVR. Cohort B criteria In cohort B, patients on OAC were randomized between monotherapy and dual therapy with clopidogrel. Patients on vitamin K antagonists were advised to continue OAC during TAVR in case of low-to-intermediate thrombotic risk and to bridge with heparin in case of a high thrombotic risk. The study scheduled follow-up visits at 30 days, 6 months, and 12 months, with primary endpoints in this analysis defined as all bleeding and a composite of ischemic events consisting of stroke and myocardial infarction. Secondary endpoints included nonprocedural bleeding, major or life-threatening bleeding, minor bleeding, stroke, myocardial infarction, and all-cause death. The post hoc analysis involved combining both cohort A and cohort B in order to establish differences between sexes. Major bleeding occurred more in women Results revealed that all bleeding and the composite of myocardial infarction and stroke rates were similar between sexes (all bleeding: 106 [22.8%] women vs 121 [23.6%] men; P=0.815; ischemic events: 26 [5.6%] vs 36 [7.0%]; P=0.429). However, major, or life-threatening bleeding occurred more often in women (58 [12.5%]) vs men (38 [7.4%]; P=0.011), most of which were access site bleedings. The use of aspirin pre- and post-TAVR increased major or life-threatening bleeding in women but not in men. “In the group of patients on aspirin (cohort A), women had more major or life-threatening bleeding,” the study noted. “Also, in patients receiving aspirin monotherapy after TAVR, there was a higher major or life threatening bleeding risk in women.” Later research has showed “aspirin resistance” in women, and a paradoxical attenuation of the inhibition of platelets, the study highlighted, potentially lowering bleeding risk and increasing the ischemic risk. “Thus, differences in response between sexes are still highly controversial,” the study team said. More difference within sexes or between them? In an accompanying editorial comment, Giulia Masiero, MD, and Giuseppe Tarantini, MD, PhD, expanded on this controversy by asking whether a difference in bleeding/ischemic outcomes after TAVR exists between sexes or within each sex. “None of the several randomized controlled trials so far available exploring the role of different antithrombotic regimens after TAVR have a sex-based analysis, but one recently failed to find any sex-specific treatment effect on outcomes,” said the co-authors, from the University of Padua Medical School in Italy. “Given that and although the nature of this manuscript remains explorative and hypothesis generating, the authors have to be commended for putting forth such a large-sized analysis on the interplay among sex and antithrombotic agents and outcomes after TAVR.” The editorialists also noted that in the current analysis the authors did not correct for baseline risk or other potential confounders (e.g., left ventricular dysfunction) between sexes. A patient level pooled analysis would be useful in this regard, they added. Sources: van Bergeijk KH, van Ginkel DJ, Brouwer J, et al. Sex Differences in Outcomes After Transcatheter Aortic Valve Replacement: A POPular TAVI Subanalysis. JACC Cardiovasc. Interv. 2023;16:1095–1102. Masiero G, Tarantini G. Sex, Antithrombotics, and Outcomes After TAVR: Is There More Difference Within Sexes or Between Them? JACC Cardiovasc. Interv. 2023;16:1103–1106. Image Credit: fizkes – stock.adobe.com