Transdermal Clonidine versus Spironolactone in Resistant Hypertension

Objectives: To compare real-world cardiovascular outcomes and safety events in patients with resistant hypertension following initiation of transdermal clonidine (TC) or spironolactone. Methods: A retrospective analysis was performed using Merative MarketScan(R) Databases in the USA to identify cohorts with resistant hypertension initiating TC or spironolactone as a fourth-line agent between January 2012 and September 2024. Major Adverse Cardiovascular Events (MACE) and safety events were assessed during variable follow-up periods. Inverse probability of treatment weighting (IPTW) was applied to adjust for differences in baseline characteristics. Cox proportional hazard models were used to adjust for post-index beta-blocker utilization as a time-varying covariate for MACE outcomes. Results: The analysis included 3,113 patients in the TC cohort and 30,640 in the spironolactone cohort. After IPTW, baseline characteristics were well balanced between cohorts (standardized mean differences <0.10; mean age 60 years, 54% male). Mean follow-up was 7.1 and 10.5 months for the TC and spironolactone cohorts, respectively. After IPTW no differences in MACE outcomes were observed between the two cohorts (weighted rate ratio 1.27 [0.79-2.06]). Results were consistent after adjusting for post-index beta-blocker use. The risk of hyperkalemia was significantly lower in the TC cohort (weighted rate ratio, 0.48 [0.33-0.70]. Conclusions: In this real-world analysis, patients with resistant hypertension treated with TC have similar risk for MACE outcomes as with spironolactone, but with significantly lower risk of hyperkalemia. Thus, in patients with resistant hypertension TC appears to provide similar cardiovascular protection, with a more favorable safety profile.