Aldosterone excess is known to worsen hypertension and kidney function. Three selective aldosterone synthase inhibitors (ASIs) were evaluated in 3 phase 2 trials. In the first study, the ASI baxdrostat 2 mg orally once daily decreased systolic blood pressure (SBP) by 11.0 mmHg compared with placebo after 12 weeks in patients with treatment-resistant hypertension. In the second study including patients with uncontrolled hypertension, placebo-corrected reduction in SBP with lorundrostat 50 mg once daily was 9.6 mmHg after 8 weeks. Patients receiving thiazides and those with body mass index (BMI) > 30 kg/m² had the optimum blood pressure (BP) response to lorundrostat, whereas plasma renin activity (PRA) did not affect its antihypertensive potency. In the third trial including patients with chronic kidney disease (CKD), the ASI BI 690517 (10 mg once daily) decreased urinary albumin creatinine ratio (UACR) by 39% after 14 weeks compared with 3% reduction with placebo. Reduction in UACR was generally similar in presence or absence of concomitant treatment with empagliflozin. The 3 ASIs mildly decreased (by <15%) estimated glomerular filtration rate (eGFR) compared with placebo. The most common adverse effects of ASIs were hyperkalemia occurring in 2.9% and 7.9% among patients randomized to baxdrostat and lorundrostat, respectively versus none in the placebo groups. In patients with CKD, frequency of hyperkalemia was higher: 14.2% and 6.0% with BI 690517 and placebo, respectively. Adrenal insufficiency was reported in 1.3% of patients randomized to BI 690517 versus 1.0% with placebo. Preliminary data suggest that selective ASIs are effective in lowering BP in patients with resistant and uncontrolled hypertension and decreasing albuminuria in CKD. Phase 3 clinical trials should be conducted to assess long-term efficacy and safety of ASIs in a wide spectrum of patients with uncontrolled BP and CKD. 

Aldosterone synthase, Hyperkalemia, Hypertension, Chronic kidney disease, Albuminuria