Consequences of Recurrent Hyperkalemia on Cardiovascular Outcomes and Mortality.

Background: Hyperkalemia (HK) has been linked to serious cardiovascular (CV) outcomes, but the impact of recurrent HK on these outcomes is ill-defined.

Objectives: This study evaluated mortality and CV outcomes associated with recurrent HK vs normokalemia in patients with chronic kidney disease (CKD) and in a subset of patients with co-occurring heart failure (HF).

Methods: REVOLUTIONIZE III was a retrospective cohort study of adults (aged ≥18 years) diagnosed with stage 3/4 CKD, with or without HF in Optum's deidentified Market Clarity database (January 2016 to August 2022). Patients with recurrent HK (≥2 events) were exactly and propensity score-matched to patients with normokalemia (no serum [K+] <3.5 or >5.0 mmol/L or HK diagnosis ever). The primary endpoint was all-cause mortality; secondary endpoints were CV outcomes including major adverse CV events plus (major adverse cardiovascular event or hospitalization with heart failure [MACE+]; defined as all-cause mortality or hospitalized myocardial infarction, stroke, or HF and hospitalized arrhythmia). Cause-specific Cox proportional hazard models were used to compare outcomes between cohorts.

Results: The study included 6,337 matched pairs overall, including 2,129 with HF. Characteristics of the samples were well-balanced. Recurrent HK was associated with higher risks of all-cause mortality (HR overall: 1.29 [95% CI: 1.20-1.38]; HF substudy: 1.30 [95% CI: 1.18-1.44]), MACE+ (overall: 1.53 [95% CI: 1.43-1.65]; HF substudy: 1.45 [95% CI: 1.29-1.64]), and hospitalized arrhythmia (overall: 1.94 [95% CI: 1.74-2.16]; HF substudy: 1.85 [95% CI: 1.55-2.21]) compared with normokalemia.

Conclusions: In patients with CKD, recurrent HK increased the risks of all-cause mortality, MACE+, and hospitalized arrhythmia compared with normokalemia, including in a subset of patients with HF.