Serum potassium in the PARADIGM-HF trial

João Pedro Ferreira, Ulrik M Mogensen, Pardeep S Jhund, Akshay S Desai, Jean-Lucien Rouleau, Michael R Zile, Patrick Rossignol, Faiez Zannad, Milton Packer, Scott D Solomon, John J V McMurray


AIMS: The associations between potassium level and outcomes, the effect of sacubitril-valsartan on potassium level, and whether potassium level modified the effect of sacubitril-valsartan in patients with heart failure and a reduced ejection fraction were studied in PARADIGM-HF. Several outcomes, including cardiovascular death, sudden death, pump failure death, non-cardiovascular death and heart failure hospitalization, were examined.

METHODS AND RESULTS: A total of 8399 patients were randomized to either enalapril or sacubitril-valsartan. Potassium level 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 ≥5.5 mmol/L) in various statistical models. Hyperkalaemia was defined as K+  ≥5.5 mmol/L and hypokalaemia as K+  ≤3.5 mmol/L. Compared with potassium 4.1-4.9 mmol/L, both hypokalaemia [hazard ratio (HR) 2.40, 95% confidence interval (CI) 1.84-3.14] and hyperkalaemia (HR 1.42, 95% CI 1.10-1.83) were associated with a higher risk for 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 levels.

CONCLUSIONS: Although both higher and lower potassium levels were independent predictors of cardiovascular death, potassium abnormalities may mainly be markers rather than mediators of risk for death.

TidsskriftEuropean Journal of Heart Failure
Udgave nummer11
Sider (fra-til)2056-2064
Antal sider9
StatusUdgivet - nov. 2020


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