To bind or not to bind: potassium-lowering drugs in heart failure

This editorial refers to ‘Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial’[†][1], by B. Pitt et al. , on page 820 More than a decade ago the first large randomized controlled trial studying the effects of spironolactone in heart failure patients was published.1,2 The Randomized Aldactone Evaluation Study (RALES) trial showed for the first time the robust effects of aldosterone receptor blockers on reducing mortality. In this landmark trial patients with systolic heart failure in New York Heart Association (NYHA) class III were included. It is well known that one of the potential serious side effects of spironolactone is hyperkalaemia. Therefore patients with potassium levels >5 mmol/L were excluded from participation in RALES and potassium levels were measured frequently. Probably because of these intense safety checks the incidence of serious hyperkalaemia was extremely low and occurred in only 2% of the patients randomized to spironolactone compared with 1% in the placebo group. Similar findings were observed in the EPHESUS trial, which studied the effects of eplerenone, a selective aldosterone receptor blocker, in myocardial infarction complicated by heart failure.3 Blocking the aldosterone receptor resulted in a significant reduction in all-cause mortality. However, serious hyperkalaemia (>6.0 mmol/L) rates … [1]: #fn-2