Patiromer vs. Placebo to Enable Spironolactone in Patients with Resistant Hypertension and Chronic Kidney Disease (AMBER): Results in Prespecified Subgroups

Abstract

Introduction Spironolactone (SPIRO) is effective at reducing blood pressure (BP) in patients (pts) with uncontrolled resistant hypertension (RHTN); however, its use in pts with chronic kidney disease (CKD) may be limited by hyperkalemia. Hypothesis Results of AMBER showed that patiromer (PAT) enabled more persistent use of SPIRO in pts with advanced CKD and RHTN. We hypothesize that PAT will also enable more persistent SPIRO use in clinically relevant prespecified subgroups. Methods This multicenter, randomized, double-blind, placebo (PBO)-controlled study recruited outpatients with CKD (estimated GFR 25-≤45 mL/min/1.73 m2) and uncontrolled RHTN. Pts were randomly assigned (1:1) to receive either PBO or PAT, and SPIRO 25 mg once daily, with dose titrations permitted after 1 wk (PAT) and 3 wks (SPIRO). The primary (between-group difference at wk 12 in the proportion of pts on SPIRO) and secondary (between-group least squares mean [LSM] difference in unattended systolic automated office BP [AOBP] to wk 12) endpoints were assessed in prespecified subgroups, including by age ( Results 295 pts were randomized to SPIRO plus either PBO (n=148) or PAT (n=147). In the overall population, baseline mean (SD) systolic BP (mmHg) was 144.9 (7.0) and 143.3 (6.5) and mean (SD) serum potassium (mEq/L) was 4.69 (0.37) and 4.74 (0.36), for the PBO and PAT groups, respectively. Consistent with results seen in the overall population, there was ∼20% difference between PAT and PBO in the % of pts remaining on SPIRO at wk 12 across subgroups, with no interaction between subgroups (Figure). Overall, systolic AOBP decreased from baseline by 10.8 mmHg (95% CI: -13.2, -8.3) for PBO and by 11.7 (95% CI: -14.1, -9.3) for PAT (both p Conclusion PAT enabled more persistent use of SPIRO in pts with advanced CKD and RHTN across all prespecified subgroups, including by age, baseline eGFR, and presence/history of diabetes and heart failure.