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
Authors: Foschi Matteo , D’Anna Lucio , De Matteis Eleonora , De Santis Federico , Romoli Michele , Tassinari Tiziana , Saia Valentina , Cenciarelli Silvia , Bedetti Chiara , Padiglioni Chiara , Censori Bruno , Puglisi Valentina , Vinciguerra Luisa , Guarino Maria , Barone Valentina , Zedde Marialuisa , Grisendi Ilaria , Diomedi Marina , Bagnato Maria Rosaria , Petruzzellis Marco , Mezzapesa Domenico Maria , Di Viesti Pietro , Inchingolo Vincenzo , Cappellari Manuel , Zivelonghi Cecilia , Candelaresi Paolo , Andreone Vincenzo , Rinaldi Giuseppe , Bavaro Alessandra , Cavallini Anna , Moraru Stefan , Piscaglia Maria Grazia , Terruso Valeria , Mannino Marina , Pezzini Alessandro , Frisullo Giovanni , Muscia Francesco , Paciaroni Maurizio , Mosconi Maria Giulia , Zini Andrea , Leone Ruggiero , Palmieri Carmela , Cupini Letizia Maria , Marcon Michela , Tassi Rossana , Sanzaro Enzo , Papiri Giuli , Paci Cristina , Viticchi Giovanna , Orsucci Daniele , Falcou Anne , Beretta Simone , Tarletti Roberto , Nencini Patrizia , Rota Eugenia , Sepe Federica Nicoletta , Ferrandi Delfina , Caputi Luigi , Volpi Gino , La Spada Salvatore , Beccia Mario , Rinaldi Claudia , Mastrangelo Vincenzo , Di Blasio Francesco , Invernizzi Paolo , Pelliccioni Giuseppe , De Angelis Maria Vittoria , Bonanni Laura , Ruzza Giampietro , Caggia Emanuele Alessandro , Russo Monia , Tonon Agnese , Acciarri Maria Cristina , Anticoli Sabrina , Roberti Cinzia , Manobianca Giovanni , Scaglione Gaspare , Pistoia Francesca , Fortini Alberto , De Boni Antonella , Sanna Alessandra , Chiti Alberto , Barbarini Leonardo , Caggiula Marcella , Masato Maela , Del Sette Massimo , Passarelli Francesco , Bongioanni Maria Roberta , De Michele Manuela , Ricci Stefano , Ornello Raffaele , Sacco Simona , Valente Martina , Paolucci Silvia , Biscetti Leonardo , Cameriere Valentina , Ponente Eleonora , Caccamo Martina , Galotto Debora , Altomare Sergio , Giorelli Maurizio , Naldi Federica , Bassi Chiara , Faini Claudia , Ajdinaj Paola , di Giovanni Anna , Sacchini Elisa , Zito Antonio , Giossi Alessia , Cardinali Patrizio , Maria Angelocola Stefania , Tudisco Laura , Cristina Baruffi Maraia , Canessa Alessandro , Sassos Davide , Grazia Vittorini Maria , Gallo Cassarino Serena , Valcamonica Gloria , Rizzo Annalisa , Vista Marco , Menegazzo Elisabetta , Diamanti Susanna , Ferrarese Carlo , De Mase Antonio , Spina Emanuele , Fleetwood Thomas , Luca Bruzzone Gian , Genovese Antonio , Monaco Daniela , Tocco Pierluigi , Menichetti Chiara , Letteri Federica , Nannucci Serena , Pascarella Rosario , Assenza Federica , Maria Lotti Enrico , Bernabè Giorgia , Di Lisi Filomena , Maestrini Ilaria , Bonaffini Novella , Chiara Ricciardi Maria , De Fino Chiara , Giuseppa Caracciolo Nicoletta , De Michele Manuela , Scala Irene , Bellavia Simone , Paci Cristina , Puca Emanuele , Matteo Fratta Giovanni , Giuseppe Ivo , Maurizio Acampa De Franco , Cappellani Roberto , Sgarlata Eleonora , Zenorini Mara , De Luca Cristina , Perini Francesco 
Published: December 2024

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.