Association between Use of Spironolactone and Risk of Stroke in Hypertensive Patients: A Cohort Study

Objective: to investigate the relationship between the use of spironolactone and the risk of stroke in hypertensive patients. Methods: a total of 2464 spironolactone users and 12,928 non-users were identified (unmatched original cohort), and 1:1 matched pairs of 2461 spironolactone users and 2461 non-users based on propensity scores were created (propensity-score-matched cohort). Results: In the unmatched original cohort, the unadjusted analysis showed that the use of spironolactone was associated with a lower risk of total stroke (HR, 0.71; 95% CI, 0.61-0.84; p < 0.001), which was sustained in the adjusted analysis. According to stroke type, the association was with ischemic strokes (propensity-score-adjusted HR, 0.71; 95% CI, 0.59-0.85; p < 0.001) and hemorrhagic ones (propensity-score-adjusted HR, 0.63; 95% CI, 0.45-0.88; p = 0.008). Similar results were shown in the propensity-score-matched cohort. The results of the subgroup and sensitivity analyses were consistent with those of the primary analysis. The dose-response analysis demonstrated a dose-dependent association of spironolactone with a lower risk of stroke in hypertensive patients. Conclusions: The use of spironolactone was associated with a significantly lower risk of stroke events in hypertensive patients. Further research, including prospective randomized clinical trials, is needed to validate our findings.