Dyskalemia in real-world HF patients with different EF
Incidence, Predictors, and Outcome Associations of Dyskalemia in Heart Failure With Preserved, Mid-Range, and Reduced Ejection FractionLiterature - Savarese G, Xu H, Trevisan M et al. - JACC HF 2019 7(1):65-76. doi: 10.1016/j.jchf.2018.10.003
Introduction and methods
Use of medical treatments in HF may interfere with potassium levels resulting in dyskalemia (dysK) including both hypokalemia (hypoK) and hyperkalemia (hyperK) [1,2}. Data on incidence of dysK in HF patients is limited, and mainly concerns HFrEF patients included in randomized clinical trials . More information is needed of incidence of dysK in different EF types and because fear of dysK may lead to underuse of underdosing of renin-angiotensin-aldosterone system (RAAS) inhibitors. Therefore, this study examined the incidence, predictors and association with clinical outcomes of dysK in HF patients with different ejection fraction (EF) in a real-world population.
HF patients from the Swedish Heart Failure (SwedeHF) Registry  registered between January 1 2006 and December 31 2010, were enrolled in this study and their potassium levels were measured on the index date and within 1 year from the index registration. After exclusion of those with missing potassium and creatinine data, with abnormal potassium levels, with missing EF data, or on dialysis, 5848 patients were included in the analysis.
The first study outcome was 1-year incidence of hypoK or hyperK. The second outcome was 1-year risk of all-cause death, HF hospitalization, or CVD hospitalization other than HF after incidence of hypoK or hyperK. Incident hyperK and hypoK were defined as the first measurements of potassium, >5.0 and <3.5 mmol/l, respectively, and moderate or severe hyperkalemia and severe hypokalemia as >5.5 mmol/l and <3.0 mmol/l.
- 24.4% of patients experienced at least 1 hyperK occurrence within 1 year, and 10.2% had moderate or severe hyperK. Crude 1-year risk of moderate or severe hyperK was higher in HFpEF and HFmrEF patients.
- 20.3% of patients experienced at least 1 occurrence of hypoK within 1 year, and 3.7% experienced severe hypoK. Crude and adjusted risks of any hypoK were highest in HFpEF patients.
- Variables independently associated with increased hyperK were: male sex, baseline potassium 4.5 to 5.0 mmol/l, lower eGFR, hemoglobin <120 g/dl, history of diabetes, COPD, alcoholism, cancer, inpatient status, NYHA functional class ≥II, use of MRA, and nonuse of beta-blockers.
- Variables that independently predicted hypoK were: female sex, potassium 3.5 to 3.9 mmol/l, eGFR <30 ml/min/1.73 m2, hemoglobin <120 g/dl, history of myocardial infarction, atrial fibrillation, COPD, alcoholism, being an inpatient, NYHA functional class ≥III, use of diuretics, nonuse of ACE inhibitors/ARBs and beta blockers.
- Incident hyperK was associated with increased risk of death (HR: 4.03; 95% CI: 3.42 to 4.75) with similar findings across the EF spectrum.
- Incident hypoK was associated with the risk of death (HR: 3.28; 95% CI: 2.79 to 3.86)), also similar across the different EF strata. Incident hypoK was also associated with the risk of CVD hospitalization other than HF (HR: 1.83; 95% CI: 1.24 to 2.71).
In a cohort of real-world HF patients, the incidence of dysK (both hyperK and hypoK) was common and risk of moderate or severe hyperK was highest in HFpEF and HFmrEF, and risk of hypoK was highest in HFpEF. HyperK and hypoK were associated with similar predictors. Incident dysK was associated with increased mortality regardless of EF category. Incident hypoK was associated with the risk of CVD hospitalization other than HF.
These data may support tailoring of RAAS inhibitor therapy, identify patients in need of potassium monitoring and those more likely to develop dysK, and can be useful in the design of HF trials with RAAS inhibitors and potassium binder agents.
After summarizing the results, Cooper and Mentz  list the strengths of the study by Savarese et al, including the large sample size, the inclusion of the range of EF, studying both hypokalemia and hyperkalemia, and the study population from a clinical practice registry. Especially the latter is important as data from clinical trials suggest that rates of drug discontinuation or hospitalization are low in HF patients who take RAAS and experience hyperkalemia, whereas in the real-world these numbers are higher. However, as with all register study, there is the limitation of unmeasured confounders. In the study by Savarese et al, there was no mentioning of the rational, frequency or timing of measurement of potassium levels, nor of the response to dyskalemia (for example change in medication). The authors conclude that the study by Savarese et al laid the groundwork for future studies to test and implement strategies to avoid dyskalemia in HF patients.