Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials

Background Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. Methods MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. Results A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin- aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I-2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I-2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I-2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I-2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60- 1.93; p = 0.801; I-2 = 0%). Conclusion The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.