High versus low dose losartan and serum potassium: an analysis from HEAAL
Abstract
Background: Patients with HF experience frequent alterations of serum potassium. Despite the high risk of events associated with hypokalemia, hyperkalemia is feared by clinicians and often leads to interruption or discontinuation of RAAS inhibitors. Data on serum potassium of patients treated with different doses of RAAS inhibitors are scarce.
Methods: HEAAL randomized 3834 HFrEF patients intolerant to ACEi to losartan 150 (high-dose) vs. 50 (low-dose) mg/day. We studied the associations of serum potassium (baseline and time-updated) with study outcomes and the effect of the randomized treatment on serum potassium.
Results: Patients with higher baseline potassium were older, had diabetes, poorer renal function, and used MRAs more frequently. In time-updated models, hyperkalemia (>5 or ≥5.5 mmol/L) was not associated with cardiovascular death nor the composite of cardiovascular death or HF hospitalization. Hypokalemia (serum potassium ≤3.5 mmol/L, in particular) was associated with a higher risk of the composite of cardiovascular death or HF hospitalization (HR 1.58, 95%CI 1.19-2.08), all-cause death (HR 1.68, 95%CI 1.26-2.24) and sudden cardiac death or resuscitated cardiac arrest (HR 1.74, 95%CI 1.11-2.73). High-dose losartan decreased the risk of hypokalemia (HR 0.77, 95%CI 0.63-0.92) and increased the risk of hyperkalemia (HR 1.21, 95%CI 1.05-1.39). High-dose losartan reduced the composite of cardiovascular death or HF hospitalizations consistently across the full spectrum of serum potassium at baseline (interaction P-value =0.85).
Conclusions: In HFrEF patients intolerant to ACEi and treated with either high- or low-dose losartan, incident hypokalemia had a stronger association with poor outcomes than incident hyperkalemia. High-dose losartan reduced the incidence of hypokalemia, and its benefits were maintained across the full spectrum of serum potassium.
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