Purpose: Patients (pts) with heart failure (HF) and chronic kidney disease (CKD) are at risk for hyperkalemia (HK), especially when treated with renin angiotensin aldosterone system inhibitors (RAASi). Patiromer, the active moiety of which is a nonabsorbed potassium (K+)-binder, was previously shown in clinical trials to lower serum K+ (s-K+) with good gastrointestinal tolerability. This was a two-phase multicenter international study in 243 pts with HK and an eGFR 15-<60 mL/min/1.73m2 with/without HF on RAASi. This prespecified subgroup analysis presents the findings in CKD pts with (n = 102) and without HF (n = 141).
Methods: Phase 1, a 4-wk single-blind treatment study, assessed patiromer for HK treatment. Phase 2, an 8-week placebo-controlled randomized withdrawal study, assessed whether chronic patiromer treatment prevented recurrent HK. Primary outcomes were change from baseline in s-K+ (Phase 1) and the between group difference in change in s-K+ from Phase 2 Baseline to Phase 2 Wk 4 (Phase 2). Secondary outcomes included the proportion with s-K+ in the target range (Phase 1) and the proportion with recurrent HK (Phase 2).
Results: The mean (±SE) change in s-K+ from baseline to week 4 was −1.06 ± 0.05 mEq/L (95% CI, −1.16 to −0.95, p < 0.001) in pts with HF and −0.98 ± 0.04 (95% CI, −1.06 to −0.90, p < 0.001) in pts without HF (p value for interaction, 0.22). Serum K+ was controlled (3.8-<5.1 mEq/L) at the end of Phase 1 in 76% of HF and 75% of non-HF pts. Primary endpoint results for Phase 2 are shown in the Table. Significantly (p < 0.001) more placebo than patiromer pts (HF, 52% vs 8%; non-HF, 66% vs 23%) developed recurrent HK (s-K+ >5.5 mEq/L) during Phase 2. Patiromer was well tolerated; constipation (none severe) was the most common adverse event with patiromer in both pts with/without HF (11% and 4% in Parts 1 and 2, respectively).
Conclusions: Patiromer provided effective s-K+ control and, compared to placebo, decreased HK recurrence in CKD pts with and without HF, with a well-tolerated safety profile that may allow continuous management of s-K+ in HF pts with HK on RAASi.