Potassium-Binding Agents to Facilitate Renin-Angiotensin-Aldosterone System Inhibitor Therapy

Abstract

Objective: To evaluate safety and efficacy data for potassium-binding resins in renin-angiotensin-aldosterone system (RAAS)-associated hyperkalemia. Data Sources: A search of MEDLINE (EBSCOhost; 1946 to February 2016) was conducted using the terms hyperkalemia, rennin-angiotensin-aldosterone system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonists, resin, and binder. Results were limited to human trials in English language journals. References of identified articles were reviewed to identify other relevant articles. Study Selection and Data Extraction: Concurrent potassium-binding agents and RAAS inhibitor use literature were reviewed. Inclusion criteria a 2-week minimum therapy duration with hyperkalemia or high-risk patients receiving concurrent RAAS-inhibiting agents. Seven articles met inclusion criteria: 1 retrospective case series for sodium polystyrene sulfonate (SPS), 1 noncontrolled study using patiromer, and 5 randomized, placebo-controlled trials using 3 different agents—2 patiromer, 2 sodium zirconium cyclosilicate (SZC), and 1 cross-linked polyelectrolyte (CLP). Data Synthesis: SPS efficacy data are limited to a mean potassium reduction of 1.8 mEq/L in a 14-patient uncontrolled case series. CLP did not reduce hyperkalemia incidence compared with placebo. Patiromer effectively maintained potassium at 0.45 to 0.72 mmol/L lower than placebo while allowing spironolactone dose titration in more patients (91% vs 74%, P = 0.019). SZC also safely and effectively normalized and maintained potassium levels in patients receiving RAAS inhibitors (71%-85% vs 48% for placebo, P < 0.01). Conclusions: Currently, the literature does not support SPS and CLP for preventing RAAS inhibitor–associated hyperkalemia. Patiromer and SZC safely and effectively lower serum potassium and prevent hyperkalemia redevelopment in patients receiving RAAS inhibitors for up to 4 and 8 weeks,0 respectively.