Abstract
AIMS: Patients with heart failure (HF) at high risk for hyperkalaemia are underrepresented in prospective HF registries. The CARE-HK in HF registry sought to characterize prospectively the clinical profile, management, and outcomes for patients with HF at high risk of hyperkalaemia. METHODS AND RESULTS: CARE-HK in HF was a multinational prospective registry of outpatients with HF (regardless of left ventricular ejection fraction [LVEF]) treated with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI) and either receiving or potential candidate for a mineralocorticoid receptor antagonist (MRA). All patients were at increased risk of hyperkalaemia, defined as hyperkalaemia at baseline, prior hyperkalaemia, or estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m(2). Outcomes included frequency of hyperkalaemic events (defined by clinician report with associated potassium value), achievement of renin-angiotensin system inhibitor (RASi) optimization (defined as ≥50% target doses for ACEI/ARB/ARNI and MRA), medication changes following hyperkalaemic episodes, and clinical events. Overall, 2558 patients from 111 sites across nine countries were included. Median (25th-75th) age was 73 (65-80) years, 32% were women, 61% had LVEF ≤40%, and 40% had prior laboratory evidence of hyperkalaemia. Median baseline eGFR and serum potassium were 44 (33-60) ml/min/1.73 m(2) and 5.0 (4.4-5.3) mEq/L, respectively. Over a median follow-up of 12.3 (9.4-18.1) months, 29% of patients had a hyperkalaemic event, and 7% had multiple events. In characterizing treatment prescribed for most of follow-up, 29% of patients received optimal RASi/MRA therapy, 69% received suboptimal RASi/MRA therapy, and 3% received no RASi/MRA. In the 30 days following the first hyperkalaemic event, RASi/MRA was down-titrated or discontinued in 3.6% of cases. Potassium binder use was low (patiromer 9.1%, sodium zirconium cyclosilicate 5.9%). Compared with patients without a hyperkalaemic event, patients experiencing a hyperkalaemic event had similar risk of all-cause mortality (hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.92-1.62, p = 0.16) and a higher risk of subsequent hospitalization (HR 1.59, 95% CI 1.35-1.86, p < 0.001). CONCLUSIONS: In this contemporary multinational prospective registry of patients with HF at high risk for hyperkalaemia, hyperkalaemic events were common but infrequently associated with RASi/MRA modification or potassium binder use. Fewer than one in three patients received optimal RASi/MRA therapy for the majority of follow-up, and hyperkalaemic events were associated with higher risk of adverse clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04864795.