Risk of bleeding, hemorrhagic stroke notably higher in women than men after PCI

Women face a greater risk of bleeding and hemorrhagic stroke after percutaneous coronary intervention (PCI) than men, according to a new subgroup analysis of the GLOBAL LEADERS trial.

The analysis, led by Ply Chichareon, MD, and published in JAMA Cardiology Nov. 6, also found that while ticagrelor monotherapy was linked to a lower risk of bleeding than dual antiplatelet therapy (DAPT) one year after PCI in men, that same benefit wasn’t replicated in female cohorts. Sex differences in the pathophysiology, presentation and prognosis of coronary artery disease (CAD) are well-established, Chichareon, of Amsterdam UMC at the University of Amsterdam, and co-authors wrote in the journal, with women historically seeing poorer short- and long-term outcomes than men.

Still, PCI exists as an effective CAD therapy for both sexes, helped largely by technical improvements in imaging-guided and physiology-guided revascularization, second-generation drug-eluting stents and potent P2Y12 inhibitors.

“Potent P2Y12 inhibitors increase the risk of bleeding, and the optimal strategy of antiplatelet therapy after PCI is still a matter of debate,” Chichareon and colleagues said. “Notably, cessation of antiplatelet therapy is more common in women than men, and being a woman has been identified as an independent predictor for bleeding after PCI.”

The team launched their study with the goal of assessing the relationship between sex and patient outcomes at two years after contemporary PCI with the efficacy and safety of two antiplatelet strategies. They drew from the randomized GLOBAL LEADERS study, a 2018 trial that enrolled 15,991 unselected patients undergoing PCI between 2013 and 2015 and found that ticagrelor monotherapy after one month of DAPT with aspirin was safe but not superior to conventional DAPT for reducing adverse outcomes in patients.

Participants in the GLOBAL LEADERS trial were randomized to either an experimental or reference antiplatelet strategy, the former being one month of DAPT followed by 23 months of ticagrelor monotherapy and the latter being 12 months of DAPT followed by 12 months of aspirin monotherapy. Chichareon et al.’s primary endpoint was a composite of all-cause mortality and new Q-wave MI at two years; their secondary endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding.

The researchers included 15,968 patients in their analysis, 23.3% of whom were women. They found the risk of the primary endpoint at two years was similar between women and men, but compared with men, women saw a 32% increased risk of BARC type 3 or 5 bleeding and a nearly five-fold increased risk of hemorrhagic stroke two years after their procedure.

The authors didn’t identify any between-sex difference in the efficacy and safety of either antiplatelet strategy two years down the line, but they did report that at one year, compared with DAPT, ticagrelor monotherapy was linked to a 28% reduced risk of bleeding in men, but not in women.

“This study reveals that women undergoing PCI are at higher risk of major bleeding and hemorrhagic stroke than men,” Chichareon and colleagues wrote. “This difference persists after adjustment for confounders, confirming that sex is an independent predictor for major bleeding after PCI.

“Therefore, our findings question the predictive ability of bleeding risk scores where sex is not included and emphasizes the need for external validation of bleeding risk scores in contemporary PCI practice."