PATIROMER VS PLACEBO TO ENABLE SPIRONOLACTONE IN PATIENTS WITH RESISTANT HYPERTENSION AND CKD: ANALYSIS ACCORDING TO PATIENT SEX (AMBER TRIAL)

Abstract

Objective: Spironolactone (SPIRO) effectively reduces BP in patients (pts) with resistant hypertension (RHTN), but hyperkalaemia (HK) may limit its use in pts with advanced CKD. In AMBER, patiromer (PAT) enabled more persistent SPIRO use in pts with RHTN and eGFR 25– < = 45 mL/min/1.73 m2. As biological differences between men and women may contribute to variations in drug response, we evaluated the AMBER results by sex in a prespecified analysis. Design and method: AMBER was a randomised, double-blind, placebo (PBO)-controlled RCT in adults with eGFR 25– < = 45 mL/min/1.73 m2 and uncontrolled RHTN (unattended systolic automated office blood pressure [AOBP]) 135–160 mm Hg, despite taking > = 3 antihypertensives. Pts were assigned (1:1) to receive PBO or PAT, and SPIRO 25 mg QD, to start along with their baseline (BL) BP medications. Dose titrations were permitted after 1 week for PAT/PBO and after 3 weeks for SPIRO. The primary endpoint (between-group difference at Wk 12 in % of pts on SPIRO) was assessed in prespecified subgroups by sex. Results: Of 295 pts randomised, there were 153 (51.9%) men and 142 (48.1%) women with BL mean (SD) systolic AOBP of 144.6 (6.7) mmHg and 143.5 (6.8) mmHg and serum K+ of 4.77 (0.37) mmol/L and 4.65 (0.35) mmol/L, respectively. More pts treated with PAT than PBO remained on SPIRO at Wk 12 in both subgroups (between treatment difference of 19.3% [P = 0.0035] for men and 19.7% [P = 0.0065] for women with P = 0.80 for interaction between subgroups) (Figure). LS Mean (SE) cumulative SPIRO dose was higher with PAT than PBO, by 449 (180) mg in men and 326 (178) mg in women. Similar reductions in AOBP were observed in both subgroups at 12 weeks (P < 0.0001). Adverse events occurred in 52% (PBO) and 53% (PAT) of men and 55% (PBO) and 59% (PAT) of women. One PBO (woman) and 3 PAT pts (2 men, 1 woman) had serum Mg 0.49 to < 0.58 mmol/L; none had serum Mg < 0.49 mmol/L. Conclusions: SPIRO reduced AOBP in pts with advanced CKD and RHTN and PAT enabled more of these pts to continue treatment with SPIRO, regardless of sex.