Serum potassium in the PARADIGM‐HF trial

Abstract

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.

2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

“…Hyperkalaemia is defined as serum potassium >5 mmol/L and can be classified as mild (>5.0 to <5.5 mmol/L), moderate (5.5 to 6.0 mmol/L), or severe (>6.0 mmol/L) 761 . It is associated with an increased risk of hospitalization and death 753 , 754 , 756 , 757 , 762 , 763 . Hyperkalaemia can be associated with the administration of RAAS inhibitors, CKD and increased absorption 761 .…”

Prevalence, Incidence, and Outcomes of Hyperkalaemia in Patients with Chronic Heart Failure and Reduced Ejection Fraction from a Spanish Multicentre Study: SPANIK-HF Design and Baseline Characteristics

“…In HFrEF, the relationship between potassium (K + ) concentration and adverse outcomes appears to be U-shaped, where both low- and high-K + levels are associated with negative effects [ 6 , 7 ]. However, it remains unclear to what extent dyskalaemia is a risk factor itself rather than a risk marker representing the patients’ overall clinical status, other comorbidities, and/or use or non-use of HF medication [ 8 ].…”

January 2022 at a glance: time for the new ESC guidelines on heart failure

“…Potassium abnormalities are associated with a worse prognosis 27,28 . Patiromer, a novel potassium binder, is a valuable option in patients with hyperkalaemia and may favour the implementation of treatment with renin–angiotensin–aldosterone system inhibitors (RAASi).…”