Aldosterone synthase inhibitors for resistant or uncontrolled hypertension: a network meta-analysis of randomized clinical trials

Abstract

Resistant hypertension is a challenging condition and linked with considerable morbidity. We aimed to evaluate the efficacy and safety of aldosterone synthase inhibitors (ASIs) among patients with resistant hypertension. Four electronic databases were searched to identify randomized clinical trials (RCTs) evaluating ASIs compared with placebo for resistant hypertension. A frequentist network meta-analysis was conducted. Continuous outcomes were reported as mean differences and dichotomous outcomes as risk ratio, each with 95% confidence interval (95% CI), using a random-effect model. The primary outcomes were changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). A total of 2725 patients from six RCTs were included. Baxdrostat and Lorundrostat significantly reduced SBP (Baxdrostat: MD -8.81 mmHg, 95% CI -10.94 to -6.67; Lorundrostat: MD -8.42 mmHg, 95% CI -11.05 to -5.78) and DBP (Baxdrostat: MD -3.28 mmHg, 95% CI -4.68 to -1.87; Lorundrostat: MD -3.13 mmHg, 95% CI -4.27 to -1.98). In contrast, Osilodrostat did not show a significant difference in SBP or DBP compared with placebo. Baxdrostat and Lorundrostat were associated with significant increases in serum potassium levels and hyperkalemia. None of the three drugs significantly increased the risk of serious adverse events. Highly selective ASIs (Baxdrostat and Lorundrostat) significantly lowered BP in patients with resistant hypertension without increasing the risk of serious adverse events, whereas the nonselective agent Osilodrostat did not reach significant difference. These findings suggest that selective aldosterone synthase inhibition represents a promising therapeutic option for resistant hypertension.