Sex Differences Among Patients With High Risk Receiving Ticagrelor With or Without Aspirin After Percutaneous Coronary Intervention

Abstract

IMPORTANCE Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI).OBJECTIVE To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin. DESIGN, SETTING, AND PARTICIPANTSThis was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020.INTERVENTIONS At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor. MAIN OUTCOMES AND MEASURESThe primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke. RESULTSOf 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P = .01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P = .12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P = .02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P < .001; P for interaction = .69). Ischemic end points were similar between treatment groups in both sexes.CONCLUSIONS AND RELEVANCE These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men.

Coronary Artery Disease in Women: A Comprehensive Appraisal

“…The TWILIGHT study assessed early aspirin withdrawal with the continuation of ticagrelor after percutaneous coronary intervention (PCI) in patients at high risk for bleeding or ischemic events. Early aspirin withdrawal with the continuation of ticagrelor was associated with a lower bleeding rate amongst both sexes with no increased risk of ischemic events [73]. Thus, this treatment strategy could potentially have a specific advantage in women.…”

Secondary Prevention of Cardiovascular Disease in Women: Closing the Gap

“…[ 87 , 88 ] Among individuals at high risk of bleeding after percutaneous coronary intervention (PCI), one emerging strategy is to stop aspirin after 3 months of DAPT and to continue with a P2Y 12 inhibitor as monotherapy. [ 89 ] In the TWILIGHT study, which tested this strategy, women did have higher bleeding rates after PCI than men, but this was largely due to differences in baseline characteristics. [ 89 ] There was no difference between women and men with regard to the benefit of early aspirin withdrawal and ticagrelor monotherapy on ischaemic endpoints.…”

“…[ 89 ] In the TWILIGHT study, which tested this strategy, women did have higher bleeding rates after PCI than men, but this was largely due to differences in baseline characteristics. [ 89 ] There was no difference between women and men with regard to the benefit of early aspirin withdrawal and ticagrelor monotherapy on ischaemic endpoints. [ 89 ]…”

“…[ 89 ] There was no difference between women and men with regard to the benefit of early aspirin withdrawal and ticagrelor monotherapy on ischaemic endpoints. [ 89 ]…”

Sex-based outcomes in contemporary antiplatelet therapy trials

“…A prespecified secondary analysis assessed outcomes by sex. 22 A total of 7119 patients with a mean age of 63.9 years were included 23.9% of women. Women were older (65.5 years vs 63.4 years), with a significantly higher prevalence of CKD (21.2% vs 14.7%) and anaemia.…”