Spironolactone and clinical outcomes in patients with alcohol use disorder and comorbid hypertension: a target trial emulation study

Abstract Rationale Alcohol use disorder (AUD) is a major contributor to the global burden of disease, yet treatments are limited. Therefore, developing evidence-based pharmacotherapies for AUD is critical. Preclinical and clinical studies suggest that spironolactone reduces alcohol intake and could be repurposed for AUD. Objective To examine associations of spironolactone prescription with AUD remission and alcohol intoxication in a real-world population. Method Target trial emulations were conducted using a population-based analytics platform of electronic health records from over 100 million US patients (TriNetX). Patients with AUD and comorbid hypertension, without prior documented AUD remission, who were prescribed spironolactone were compared with propensity-score matched controls prescribed other antihypertensive medications. The studied outcomes were AUD remission and alcohol intoxication, identified by International Classification of Diseases codes during a one-year follow-up. Results Spironolactone prescription was associated with a significantly higher hazard rate for AUD remission compared with prescriptions for all other groups of antihypertensive medications, with hazard ratios ranging from 1.24 95% confidence interval (CI): 1.06–1.45 compared to loop diuretics and 2.07 95% CI: 1.73–2.48 compared to angiotensin II receptor blockers. Furthermore, spironolactone prescriptions were associated with a significantly lower hazard rate for alcohol intoxication compared with most other groups of antihypertension medications. Conclusion Patients prescribed spironolactone were more likely to experience AUD remission and less likely to experience alcohol intoxication compared with propensity score-matched controls. These real-world findings further support the potential of spironolactone as a new pharmacotherapy for AUD and underscore the need for further testing in randomized controlled trials.