Exploring Sex Differences in Outcomes of Dual Antiplatelet Therapy for Patients With Noncardioembolic Mild-to-Moderate Ischemic Stroke or High-Risk Transient Ischemic Attack: A Propensity-Matched Analysis of the READAPT Study Cohort.

Background: Sex may impact clinical outcomes in patients with stroke treated with dual antiplatelet therapy (DAPT). We aimed to investigate the sex differences in the short-term outcomes of DAPT within a real-world population of patients with noncardioembolic mild-to-moderate ischemic stroke or high-risk transient ischemic attack.
Methods: We performed a propensity score-matched analysis from a prospective multicentric cohort study (READAPT [Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack]) by including patients with noncardioembolic mild-to-moderate stroke (National Institutes of Health Stroke Scale score of 0-10) or high-risk transient ischemic attack (age, blood pressure, clinical features, duration of transient ischemic attack, presence of diabetes [ABCD ₂ ] ≥4) who initiated DAPT within 48 hours of symptom onset. The primary effectiveness outcome was the 90-day risk of new ischemic stroke or other vascular events. The secondary effectiveness outcomes were the 90-day modified Rankin Scale score ordinal shift, vascular and all-cause mortality, and 24-hour early neurological improvement or deterioration. The safety outcomes included the 90-day risk of moderate-to-severe and any bleeding, symptomatic intracranial hemorrhage, and 24-hour hemorrhagic transformation. Outcomes were compared between sexes using Cox and generalized ordinal logistic regression analyses, along with calculating risk differences and ratios.
Results: From 2278 patients in the READAPT study cohort, we included 1643 mild-to-moderate strokes or high-risk transient ischemic attacks treated with DAPT (mean age, 69.8±12.0 years; 34.3% women). We matched 531 women and men. The 90-day risk of new ischemic stroke or other vascular events was significantly lower among women than men (hazard ratio, 0.53 [95% CI, 0.28-0.99]; P =0.039). There were no significant differences in secondary effectiveness outcomes. The 90-day risk of safety outcomes was extremely low and did not differ between women and men (moderate-to-severe bleedings: 0.4% versus 0.8%; P =0.413; symptomatic intracranial hemorrhage: 0.2% versus 0.4%; P =0.563). Subgroup analysis for primary effectiveness outcome showed a lower 90-day risk of new ischemic stroke or other vascular events among women aged <50 years, baseline National Institutes of Health Stroke Scale score of 0 to 5, prestroke modified Rankin Scale score <2, large artery atherosclerosis cause, and no diabetes.
Conclusions: Our findings suggest that women with noncardioembolic mild-to-moderate stroke or high-risk transient ischemic attack treated with DAPT may have lower short-term risk of recurrent ischemic events than men. Further research is needed to understand the mechanisms behind potential sex-based differences in outcomes after DAPT use.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.
Competing Interests: Dr Piscaglia reports grants from Sanofi Genzyme, Roche Health Solutions, Inc, Novartis Pharma, Biogen, and Merck Company Foundation. Dr Paciaroni reports compensation from Boehringer Ingelheim, PFIZER CANADA INC, Bristol-Myers Squibb; iRhythm Technologies; SANOFI-AVENTIS U.S. LLC, and Daiichi Sankyo Europe GmbH for other services. Dr Zini reports compensation from Bayer Healthcare for other services and Boehringer Ingelheim, Alexion Pharmaceuticals, and CSL Behring for consultant services. Dr Ornello reports grants from Novartis, Pfizer, and Allergan and compensation from Teva Pharmaceutical Industries, Eli Lilly and Company, Novartis, and H. Lundbeck A S for other services; AbbVie and Eli Lilly for data and safety monitoring services; Teva Pharmaceutical Industries for consultant services; and reports and travel support from Teva Pharmaceutical Industries. Dr Sacco reports compensation from Novartis for other services; compensation from Novo Nordisk, Boehringer Ingelheim, Teva Pharmaceutical Industries, Allergan, Novartis, PFIZER CANADA INC, Abbott Canada, H. Lundbeck A S, AstraZeneca, and Eli Lilly and Company for consultant services; and employment by Università degli Studi dell’Aquila. The other authors report no conflicts.