Effect of Patiromer in Hyperkalemic Patients Taking and Not Taking RAAS Inhibitors

Abstract

Introduction: Hyperkalemia (potassium >5.0 mEq/L) affects heart failure patients with renal disease regardless of the use of renin-angiotensin-aldosterone system inhibitors (RAASi). The open-label TOURMALINE study showed that patiromer, a sodium-free, nonabsorbed potassium binder, lowers serum potassium of hyperkalemic patients similarly when given with or without food; unlike prior studies, patients were not required to be taking RAASi. We conducted post hoc analyses to provide the first report of patiromer in patients not taking RAASi.

Methods: Hyperkalemic patients received patiromer, 8.4 g/d to start, adjusted to achieve and maintain serum potassium of 3.8 to 5.0 mEq/L. If taking RAASi, stable doses were required. The primary end point was the proportion of patients with serum potassium 3.8 to 5.0 mEq/L at week 3 or 4. This analysis presents data by patients taking or not taking RAASi.

Results: Demographics and baseline characteristics were similar in patients taking (n = 67) and not taking RAASi (n = 45). Baseline mean (SD) serum potassium was 5.37 (0.37) mEq/L and 5.42 (0.43) mEq/L in patients taking and not taking RAASi, respectively. Mean (SD) daily patiromer doses were similar (10.7 [3.2] and 11.5 [4.0] g, respectively). The primary end point was achieved in 85% (95% confidence interval [CI]: 74-93) of patients taking RAASi and in 84% (95% CI: 71-94) of patients not taking RAASi. From baseline to week 4, the mean (SE) change in serum potassium was -0.67 (0.08) mEq/L in patients taking RAASi and -0.56 (0.10) mEq/L in patients not taking RAASi (both P < .0001 vs baseline, P = nonsignificant between groups). Adverse events were reported in 26 (39%) patients taking RAASi and 25 (54%) not taking RAASi; the most common adverse event was diarrhea (2% and 11%, respectively; no cases were severe). Five patients (2 taking RAASi) reported 6 serious adverse events; none considered related to patiromer.

Conclusions: Patiromer was effective and generally well-tolerated for hyperkalemia treatment, whether or not patients were taking RAAS inhibitors.

Keywords: RAAS inhibitor; chronic kidney disease; heart failure; hyperkalemia; patiromer.

Figure 1.

TOURMALINE study design. ^aRandomization was stratified by screening K⁺, race, and history of diabetes mellitus; although patients were randomized on the morning of the baseline visit (day 1), patients did not initiate with or without food dosing until day 2. Abbreviations and symbols: ↑, scheduled blood draw; BL, baseline; F1, follow-up visit 1; F2, follow-up visit 2; HK, hyperkalemia; K⁺, potassium; QD, once daily.

Figure 2.

Disposition of patients taking and not taking RAAS inhibitors. ^aExcluded from the efficacy analysis: 1 patient who did not receive patiromer and 1 patient with a protocol violation and no postbaseline serum potassium observations. Excluded from the safety analysis: 1 patient who did not receive patiromer. HK indicates hyperkalemia; RAASi, renin–angiotensin–aldosterone system inhibitor.

Figure 3.

Forest plot of responders at either week 3 or 4 by subgroup. Responders were defined as patients achieving target serum potassium of 3.8 to 5.0 mEq/L. DM indicates diabetes mellitus; eGFR, estimated glomerular filtration rate; RAASi, renin–angiotensin–aldosterone system inhibitor.

Figure 4.

Mean (SE) serum potassium over time by baseline RAAS inhibitor use. The shaded area represents the target range for serum potassium (3.8-5.0 mEq/L). BL indicates baseline; K⁺, potassium; RAAS, renin–angiotensin–aldosterone system; SE, standard error.