Sex Differences in Midterm Prognostic Implications of High Platelet Reactivity After Percutaneous Coronary Intervention With Drug-Eluting Stents in East Asian Patients: Results From the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium

Abstract

Background Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug-eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all-cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis). HPR was more common in women (46.7%) than in men (28.1%). In propensity-adjusted models, HPR was an independent predictor of MACCEs (men with HPR: hazard ratio [HR], 1.60 [95% CI, 1.20-2.12]; women with HPR: HR, 0.99 [95% CI, 0.69-1.42]) and all-cause mortality (men with HPR: HR, 1.61 [95% CI, 1.07-2.44]; women with HPR: HR, 0.92 [95% CI, 0.57-1.50]) in men, although those associations were insignificant among women. In addition, a significant interaction between sex was noted in the associations between HPR and MACCE (P_interaction=0.013) or all-cause mortality (P_interaction=0.025). Conclusions In this study, HPR was a differential risk factor for 1-year MACCEs and all-cause mortality in women and men. And it was an independent predictor of 1-year MACCEs and all-cause mortality in men but not in women. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028. Registered July 9, 2003, https://clinicaltrials.gov/ct2/show/NCT04734028.

Keywords: coronary artery disease; drug‐eluting stent; female; platelet function; sex.

Figure 1. Study flow.

HPR indicates high platelet reactivity; PFT, platelet function test; PRU, P2Y12 reaction unit; and PTRG‐DES, Platelet Function and Genotype‐Related Long‐Term Prognosis in Drug‐Eluting Stent–Treated Patients With Coronary Artery Disease.

Figure 2. Kaplan‐Meier curve according to sex and high platelet reactivity (HPR) for clinical outcomes.

Kaplan‐Meier curves according to sex and HPR showing major adverse cardiac and cerebrovascular events (MACCEs) (A), all‐cause mortality (B), stent thrombosis (C), and major bleeding (D). HR indicates hazard ratio.

Figure 3. Association between sex, high platelet reactivity (HPR), and clinical outcomes.

HR indicates hazard ratio; and MACCE, major adverse cardiac and cerebrovascular event.

Figure 4. Sex differences in prognostic implications of high platelet reactivity (HPR) after percutaneous coronary intervention (PCI).

HPR was more common in women than men (left upper). There was no statistically significant difference between women and men in 1‐year major adverse cardiac and cerebrovascular events (MACCEs) (right upper). Compared with women, HPR is important as an independent predictor of 1‐year MACCEs and 1‐year mortality in men (lower). HR indicates hazard ratio.