Hypokalemia and Outcomes in Patients With Chronic Heart Failure and Chronic Kidney Disease

TLDR

Little is known about how hypokalemia affects outcomes in patients with chronic heart failure and chronic kidney disease. In a cohort of 7,788 heart‑failure patients, 2,793 had chronic kidney disease; among them, 527 had hypokalemia and 2,266 had normokalemia, and propensity‑score matching produced 522 patient pairs for analysis. Hypokalemia was associated with a 56% higher risk of all‑cause mortality (48% vs 36%) and increased risks of cardiovascular (HR 1.65), heart‑failure (HR 1.82), and hospitalization events, with similar excess risks observed in subgroups of mild hypokalemia and lower eGFR.

Abstract

Background— Little is known about the effects of hypokalemia on outcomes in patients with chronic heart failure (HF) and chronic kidney disease. Methods and Results— Of the 7788 patients with chronic HF in the Digitalis Investigation Group trial, 2793 had chronic kidney disease, defined as estimated glomerular filtration rate <60 mL/min per 1.73 m 2 . Of these, 527 had hypokalemia (serum potassium <4 mEq/L; mild) and 2266 had normokalemia (4 to 4.9 mEq/L). Propensity scores for hypokalemia were used to assemble a balanced cohort of 522 pairs of patients with hypokalemia and normokalemia. All-cause mortality occurred in 48% and 36% of patients with hypokalemia and normokalemia, respectively, during 57 months of follow-up (matched hazard ratio when hypokalemia was compared with normokalemia, 1.56; 95% CI, 1.25 to 1.95; P <0.0001). Matched hazard ratios (95% CIs) for cardiovascular and HF mortalities and all-cause, cardiovascular, and HF hospitalizations were 1.65 (1.29 to 2.11; P <0.0001), 1.82 (1.28 to 2.57; P <0.0001), 1.16 (1.00 to 1.35; P =0.036), 1.27 (1.08 to 1.50; P =0.004), and 1.29 (1.05 to 1.58; P =0.014), respectively. Among 453 pairs of balanced patients with HF and chronic kidney disease, all-cause mortality occurred in 47% and 38% of patients with mild hypokalemia (3.5 to 3.9 mEq/L) and normokalemia, respectively (matched hazard ratio, 1.31; 95% CI, 1.03 to 1.66; P =0.027). Among 169 pairs of balanced patients with estimated glomerular filtration rate <45 mL/min per 1.73 m 2 , all-cause mortality occurred in 57% and 47% of patients with hypokalemia (<4 mEq/L; mild) and normokalemia, respectively (matched hazard ratio, 1.53; 95% CI, 1.07 to 2.19; P =0.020). Conclusions— In patients with HF and chronic kidney disease, hypokalemia (serum potassium <4 mEq/L) is common and associated with increased mortality and hospitalization.