Patients hospitalized for acute heart failure (HF) have better 180-day survival when doses of mineralocorticoid receptor antagonists (MRAs) and angiotensin-converting enzyme inhibitors (ACEis) and/or angiotensin receptor blockers (ARBs) are increased or maintained, according to a study published in JACC Heart Failure. Incident hyperkalemia, while common during hospitalization for HF, was not linked to worse outcomes after hospital discharge.
Hospitalization for HF is typically associated with a high risk for hypokalemia due to diuretic therapy or hyperkalemia due to initiation or adjustment of doses of renin-angiotensin-aldosterone system inhibitors (RAASis). Current guidelines recommend that ACEis/ARBs and MRAs be avoided or down-titrated if serum potassium exceeds 5 mEq/L; however, little data are available on the association between incident hyperkalemia and up- or down-titration of RAASis in hospitalization for acute HF. The objective of this study was to investigate the relationship between hyperkalemia and adjustment of RAASi doses in patients hospitalized for acute HF.
In this study, researchers measured serum potassium daily until day 7 or discharge in patients hospitalized with acute HF (N=1589) who were enrolled in a separate trial. Researchers classified serum potassium concentrations <3.5 mEq/L as hypokalemia and concentrations >5 mEq/L as hyperkalemia. They defined incident hyperkalemia as ≥1 episode during hospitalization in which potassium was >5 mEq/L. The primary outcome was all-cause mortality at 180 days, and the secondary outcome was all-cause mortality through 60 days or rehospitalization for cardiovascular or renal causes.
Results revealed that concentrations of serum potassium increased from 4.3±0.6 mEq/L at baseline to 4.5±0.6 mEq/L at discharge or day 7 (P <.001). The average change in potassium during hospitalization was 0.22±0.68 mEq/L. Incident hypokalemia occurred in 17% of patients (n=265), and incident hyperkalemia occurred in 35% of patients (n=564). Of these patients, 5% (n=28) had hyperkalemia on day 1 of hospitalization, and 2% of patients (n=34) experienced both hypokalemia and hyperkalemia episodes.
Compared with patients who had incident hypokalemia or normal potassium, patients with incident hyperkalemia were more often taking MRAs (53%) and ACEis/ARBs (78%) before hospitalization. MRAs were more often down-titrated in patients with incident hyperkalemia (15%) compared with patients with incident hypokalemia (8%) or normal potassium (9%). ACEis/ARBs were not down-titrated more often in patients with incident hyperkalemia compared with patients with incident hypokalemia or patients with normal potassium (P =.296).
Overall, 17% of patients (n=269) died within 180 days and 27% of patients (n=434) experienced the secondary outcome. Mortality at 180 days was associated with down-titration of MRAs during hospitalization (hazard ratio [HR] 1.73; 95% CI, 1.15-2.6) regardless of incident hyperkalemia (P >.1). Lower 180-day mortality was observed in patients with incident hyperkalemia who were discharged on an increased or same dose of MRAs (HR 0.52; 95% CI 0.32-0.85) or ACEis/ARBs (HR 0.47; 95% CI 0.29-0.77).
The limitations of this study are as follows. The separate trial from which patients were observed excluded patients with serum potassium <3 mEq/L, and no dosing data are available for this subgroup. In addition, researchers did not record the reasons doses of RAASi were changed during hospitalization. Last, changes in RAASi were recorded only within a 7-day period, and effects of dose adjustments after this period may have affected outcomes.
The study researchers concluded that incident hyperkalemia does not result in impaired prognosis in patients hospitalized for acute HF and that patients with incident hyperkalemia who are discharged with an increased or same dose of MRAs and/or ACEis/ARBs may experience lower 180-day mortality.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Beusekamp JC, Tromp J, Cleland JGF, et al. Hyperkalemia and treatment with RAAS-inhibitors during acute heart failure hospitalizations and their association with mortality [published online October 5, 2019]. JACC Heart Fail. doi:10.1016/j.jchf.2019.07.010