Introduction: RAAS inhibitors (RAASi) reduce mortality in patients (pts) with HF ± CKD, yet hyperkalaemia (HK) can limit RAASi use in these pts. We evaluated the effect of patiromer, a novel investigational K+ binder, on serum K+ (s-K+) in HK pts with HF and advanced CKD on RAASi.
Methods: OPAL-HK (OP) was a 12-wk, 2-part, randomised, single-blind study; AMETHYST-DN (A-DN) was a 52-wk, randomised, open-label study. Eligible pts had eGFR 15–59, were on ≥1RASSi and, in A-DN, had T2DM; pts with NYHA class 4–5 HF were excluded. Entry s-K+ was 5.1-<6.5 mEq/L (OP) and >5.0-<6.0 mEq/L (A-DN). In a posthoc subgroup analysis, efficacy data were pooled over the 1st 4 wk in pts with HF and stage 3b-5 CKD and analysed for s-K+ change from baseline (1° endpoint) by s-K+ strata: >5.0–5.5 (mild) and >5.5-<6.0 mEq/L (mod/severe) in A-DN; 5.1-<5.5 (mild) and 5.5-<6.5 mEq/L (mod/severe) in OP.
Results: Of HF pts with advanced CKD, 66 had mild and 66 had mod/severe HK. Pts were primarily male (∼60%) and ≥65 yr (62%); mean±SD eGFR was 29±10 in mild and 27±9 mL/min/1.73m2 in mod/severe pts. With patiromer mean s-K+ was reduced to <5.0 mEq/L by the first post-baseline visit (Day 3) in mild HK and by wk 1 in mod/severe HK pts and continued to improve (Fig). By wk 4, mean (95% CI) s-K+ change from baseline was −0.62 mEq/L (−0.74, −0.50) in mild HK and −1.13 mEq/L (−1.28, −0.97) in mod/severe HK pts; both P<0.001. One pt developed s-K+ <3.5 mEq/L through wk 4. AEs were predominately mild-to-moderate GI complaints; AEs led to patiromer discontinuation in 6 pts in each study over the entire study period.
Conclusions: Patiromer significantly reduced s-K+ in HK patients with HF and advanced CKD over 4 wk. If approved, patiromer may be an option for HK treatment in pts with HF and advanced CKD.