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.