Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors

Abstract

Aims: We evaluated the effects of patiromer, a potassium (K(+))-binding polymer, in a pre-specified analysis of hyperkalaemic patients with heart failure (HF) in the OPAL-HK trial.

Methods and results: Chronic kidney disease (CKD) patients on renin-angiotensin-aldosterone system inhibitors (RAASi) with serum K(+) levels ≥5.1 mEq/L to <6.5 mEq/L (n = 243) received patiromer (4.2 g or 8.4 g BID initially) for 4 weeks (initial treatment phase); the primary efficacy endpoint was mean change in serum K(+) from baseline to week 4. Eligible patients (those with baseline K(+) ≥5.5 mEq/L to <6.5 mEq/L and levels ≥3.8 mEq/L to <5.1 mEq/L at the end of week 4) entered an 8-week randomized withdrawal phase and were randomly assigned to continue patiromer or switch to placebo; the primary efficacy endpoint was the between-group difference in median change in the serum K(+) over the first 4 weeks of that phase. One hundred and two patients (42%) had heart failure (HF). The mean [± standard error (SE)] change in serum K(+) from baseline to week 4 was -1.06 ± 0.05 mEq/L [95% confidence interval (CI), -1.16,-0.95; P < 0.001]; 76% (95% CI, 69,84) achieved serum K(+), 3.8 mEq/L to <5.1 mEq/L. In the randomized withdrawal phase, the median increase in serum K(+) from baseline of that phase was greater with placebo (n = 22) than patiromer (n = 27) (P < 0.001); recurrent hyperkalaemia (serum K(+), ≥5.5 mEq/L) occurred in 52% on placebo and 8% on patiromer (P < 0.001). Mild-to-moderate constipation was the most common adverse event (11%); hypokalaemia occurred in 3%.

Conclusion: In patients with CKD and HF who were hyperkalaemic on RAASi, patiromer was well tolerated, decreased serum K(+), and, compared with placebo, reduced recurrent hyperkalaemia.

Keywords: chronic kidney disease; heart failure; hyperkalaemia; patiromer.

Figure 1

Serum K⁺ levels over time during the treatment phase. a, Treatment phase primary endpoint: Mean serum K⁺ change from baseline to week 4. b, Mean serum K⁺ change from baseline to week 4 over time. Secondary endpoint: 76% and 75% of patients with and without HF, respectively, had serum K⁺ 3.8 to < 5.1 mEq/L at week 4. HF, heart failure; CI, confidence interval; K⁺, potassium; SE, standard error.

Figure 2

Effect of patiromer on serum K⁺ in patients with and without HF during the randomized withdrawal phase. †P < 0.001; CI, confidence interval; HF, heart failure; K⁺, potassium.

Figure 3

Time to first recurrence of hyperkalaemia [(a) K⁺ ≥5.1 mEq/L; (b) K⁺ ≥5.5 mEq/L] in patients with HF during the randomized withdrawal phase. Circles indicate censored observations. BL, baseline; HF, heart failure; K⁺, potassium; Wk, week.

Figure 4

Proportion of patients discontinuing RAASi therapy during the randomized withdrawal phase. (a) HF patients; (b) non‐HF patients. BL, baseline of withdrawal; HF, heart failure; RAASi, renin‐angiotensin‐aldosterone system inhibitor; Wk, week.