Eur J Heart Fail. 2020 Aug 18. doi: 10.1002/ejhf.1987. Online ahead of print.
BACKGROUND: We studied the association between potassium and outcomes, the effect of sacubitril/valsartan on potassium, and whether potassium level modified the effect of sacubitril/valsartan in patients with heart failure and a reduced ejection fraction in PARADIGM-HF.
AIMS: We examined several outcomes including cardiovascular death, sudden-death, pump-failure death, non-cardiovascular death and heart failure hospitalization.
METHODS: 8399 patients were randomized to either enalapril or sacubitril/valsartan. Potassium at randomization and follow-up was examined as a continuous and categorical variable (≤3.5, 3.6-4.0, 4.1-4.9, 5.0-5.4, and ≥5.5mmol/L) in various statistical models. Hyperkalemia was defined as K+ ≥5.5mmol/L and hypokalemia as K+ ≤3.5mmol/L.
RESULTS: Compared to potassium 4.1-4.9mmol/L, both hypokalemia (HR 2.40, 95%CI 1.84-3.14) and hyperkalemia (HR 1.42, 1.10-1.83) were associated with a higher risk of cardiovascular death. However, potassium abnormalities were similarly associated with sudden death and pump failure death, as well as non-cardiovascular death and heart failure hospitalization. Sacubitril/valsartan had no effect on potassium overall. The benefit of sacubitril/valsartan over enalapril was consistent across the range of baseline potassium.
CONCLUSIONS: Although both higher and lower potassium were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk of death.