More Bleeding Events After PCI in Women With Baseline Risk Factors

Haemorrhagic stroke. Illustration of a ruptured blood vessel in the brain causing a stroke.
The researchers explored the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin.

Baseline factors, such as older age and kidney impairment, increased bleeding risk for women compared with men who underwent percutaneous coronary intervention (PCI) and were treated with ticagrelor. Withdrawal of aspirin while continuing treatment with ticagrelor reduced bleeding events in both women and men, according to study results published in JAMA Cardiology.

In a prespecified secondary analysis of TWILIGHT, a placebo-controlled, randomized multicenter trial, the investigators sought to evaluate treatment outcomes associated with sex among patients treated with ticagrelor plus aspirin vs ticagrelor monotherapy. The primary endpoint for bleeding events was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding; the primary endpoint for ischemic events was a composite of death, myocardial infarction, or stroke.

Researchers analyzed data from 7119 patients who underwent successful PCI with drug-eluting stents from 187 sites across 11 countries. Study participants had at least 1 clinical and 1 angiographic feature associated with a high risk of bleeding or ischemic events and were adherent to ticagrelor plus aspirin for 3 months postintervention.

Participants without any major adverse events were then randomly assigned to receive ticagrelor with aspirin (852 women, 2712 men) or ticagrelor with placebo (846 women, 2709 men) for 12 more months. Models were adjusted for baseline risk factors and confounding conditions, including age, race, region, smoking status, diabetes, anemia, hypertension, chronic kidney disease, previous PCI, and more.

Women made up 23.9% (1698) of the study population, and participants’ mean [SD] age was 63.9 [10.2] years. Compared with men, women were older (65.5 [9.6] years vs 63.4 [10.3] years) and more likely to be non-White. Women had a higher prevalence of insulin-dependent diabetes, anemia, hypertension, and chronic kidney disease (21.2% vs 14.7%). On the other hand, women were less likely to be smokers or to report previous myocardial infarction, PCI, or coronary artery bypass graft surgery.

At 12 months, BARC 2, 3, or 5 bleeding occurred more often in women than in men (6.8% vs 5.2%; hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P =.01). After multivariate adjustment, associated bleeding risk for women was no longer significant (adjusted HR [aHR], 1.20; 95% CI, 0.95-1.52; P =.12). No significant differences in ischemic endpoints were reported between women and men.

In comparing treatments, ticagrelor monotherapy vs ticagrelor plus aspirin was associated with lower risk of bleeding in women (5% vs 8.6%; aHR, 0.62; 95% CI, 0.42-0.92; P =.02) and in men (3.7% vs 6.6%; aHR, 0.57; 95% CI, 0.44-0.73; P <.001). In fact, aspirin withdrawal was associated with an absolute reduction of bleeding risk for women (-3.6%; 95% CI, -6.0% to -1.2%) and in men (-2.9%; 95% CI, -4.1% to -1.7%). Rates of ischemic endpoints were similar for both aspirin and placebo groups in women (3.5% vs 3.5%; aHR, 1.04; 95% CI, 0.61-1.77; P =.88) and in men (4.0% vs 4.1%; aHR, 1.06; 95% CI, 0.80-1.39; P =.69).

The investigators suggested that differences in baseline characteristics between women and men place women who undergo PCI and receive ticagrelor at higher hemorrhagic risk. When adjusting for baseline factors, however, the risk of bleeding was similar between women and men. The researchers indicated that the benefits of continuing ticagrelor therapy without aspirin (namely, an absolute reduction in bleeding events) were comparable between women and men.

Disclosure: This work was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.


Vogel B, Baber U, Cohen DJ, et al. Sex differences among patients with high risk receiving ticagrelor with or without aspirin after percutaneous coronary intervention: a subgroup analysis of the TWILIGHT randomized clinical trial. JAMA Cardiol. Published online May 15, 2021. doi:10.1001/jamacardio.2021.1720