To evaluate the impact of various antihypertensive drugs on secondary stroke prevention in a real-life setting.

Nationwide historic cohort study.

French healthcare system data (SNDS).

Adults hospitalised for ischaemic stroke between 2014 and 2015 were followed up until December 2021 and stratified based on the presence of atrial fibrillation (AF).

Risk of stroke recurrence was assessed using a time-dependent Cox cause-specific model accounting for changes in drug exposure. We also investigated the risk of major adverse cardiovascular events (MACE) or all-cause death. Models were adjusted on stroke characteristics, coprescriptions and co-morbidities, at inclusion and across follow-up.

Among 54 764 patients without AF (median age 71; 46% women) and 17 960 with AF (median age 79; 51% women), stroke recurrence occurred in 11% and 13%, respectively. In non-AF patients, reduced recurrence risk was associated only with use of calcium channel blockers (adjusted HR (aHR) 0.91, 95% CI 0.86 to 0.97), thiazide diuretics (aHR 0.90, 95% CI 0. 83 to 0.97), loop diuretics (aHR 0.86, 95% CI 0.77 to 0.95) and potassium-sparing agents (aHR 0.83, 95% CI 0.70 to 0.98). In AF patients, only potassium-sparing agents (aHR 0.82, 95% CI 0.69 to 0.99) were associated with reduced recurrence risk. All antihypertensive drugs, apart from loop diuretics, were associated with a reduced risk of MACE or all-cause death.

In this large cohort, only diuretics and calcium channel blockers were associated with a reduced risk of recurrent stroke. Most antihypertensive drugs, however, may be more effective in overall cardiovascular prevention.