Higher Bleeding Risk In Women After PCI Mostly Due To Baseline Sex Differences

The higher bleeding risk in women compared with men receiving dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is mostly due to baseline differences between the sexes, according to a subgroup analysis of the TWILIGHT study.

In addition, in this high-risk PCI population, "the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men," the study team says.

The results were published in JAMA Cardiology and presented at ACC.21, the virtual annual meeting of the American College of Cardiology, by Dr. Birgit Vogel of the Icahn School of Medicine at Mount Sinai in New York.

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DAPT with the P2Y12-receptor inhibitor ticagrelor and aspirin decreases the risk of ischemic events after PCI but raises the risk of bleeding. Studies have shown that, compared with men, women have a higher bleeding risk after PCI.

"While these associations may reflect differences in baseline risk factors, such as older age and renal impairment that are more prevalent in women, other data suggest an independent biological effect of female sex on hemorrhagic risk may exist," Dr. Vogel noted in her presentation.

In the Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT) study, monotherapy with ticagrelor after a short period of DAPT compared with continued DAPT reduced bleeding without increasing ischemic events among patients at high risk for bleeding or ischemic events after PCI.

"Whether these effects vary in relation to sex remains unknown," Dr. Vogel said.

The researchers explored sex differences and evaluated the association of sex with outcomes among patients treated with ticagrelor monotherapy versus ticagrelor plus aspirin in a subgroup analysis of TWILIGHT.

Three months after PCI, 7,119 adults (mean age, 63.9 years; 23.9% women) adherent to ticagrelor plus aspirin without major adverse event were randomly allocated to either aspirin or placebo for an additional 12 months along with ticagrelor.

Compared with men, women were significantly older (65.5 vs. 63.4 years) and significantly more likely to have chronic kidney disease (21.2% vs. 14.7%), anemia (23.2% vs. 18.3%) and hypertension (76.5% vs. 71.1%).

The primary bleeding endpoint (BARC type 2, 3, or 5 bleeding at 12 months after randomization) occurred more often in women than men (6.8% vs. 5.2%; hazard ratio, 1.32; 95% confidence interval: 1.06 to 1.64).

But after multivariable adjustment, the bleeding risk in women was no longer significantly higher than in men (adjusted HR, 1.20; 95% CI, 0.95 to 1.52).

There was no significant difference between women and men in the primary ischemic endpoint (a composite of death, myocardial infarction, or stroke: 3.5% and 4.0%, respectively; adjusted HR, 0.87; 95% CI, 0.64 to 1.18).

In comparing the two treatment strategies in women and men, compared with ticagrelor plus aspirin, ticagrelor plus placebo was associated with significantly lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62) and men (adjusted HR, 0.57).

"The relative risk reduction associated with early aspirin withdrawal was similar between sexes at around 40%," Dr. Vogel said.

Discussant for the study, Dr. Jacqueline Tamis-Holland, of Icahn School of Medicine at Mount Sinai, said this is a "really interesting" analysis.

"What we know is that women notoriously have higher bleeding risk than men," she noted. Yet this analysis "did not show any differences in bleeding risk after adjusting for other confounding variables. And in fact, one would think that the relative benefit of a treatment that's designed to decrease bleeding would be more favorable in women because women are at higher bleeding risk. And in fact, (the researchers) didn't show that."

Dr. Vogel said it's important to note several limitations of the analysis. Neither of the sex-specific subgroups was individually powered to draw definitive conclusions on the effect of ticagrelor monotherapy versus ticagrelor plus aspirin on outcome.

The findings are also specific to a PCI population at high risk for bleeding or ischemic events. Finally, she noted that the analyses considered only patients who tolerated an initial three months of DAPT with ticagrelor plus aspirin without any major adverse events.

"Our findings should motivate dedicated studies to further explore the benefits of early aspirin withdrawal in women," Dr. Vogel concluded.

—Megan Brooks

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