Risk of developing hyperkalemia in patients with hypertension treated with combination antihypertensive therapy – a retrospective register-based study

Abstract

Background The risk of hyperkalemia in relation to different combinations of antihypertensive therapy remains to be elucidated.Methods In this Danish register-based study, we aimed to investigate the risk of developing hyperkalemia in relation to different combinations of antihypertensive therapy. Using incidence density matching, we matched a hyperkalemic patient to five normokalemic patients on renal function, age, sex, and time between study entry and date of potassium measurement. Combination therapies were subdivided into eight groups: beta blockers (BB) + calcium channel blockers (CCB), BB + renin angiotensin system inhibitors (RASi), BB + RASi + mineralocorticoid receptor antagonists (MRA), CCB + RASi, CCB + RASi + thiazides, CCB + thiazides, RASi + thiazides, and other combinations. Multivariable conditional logistic regression was used to estimate the odds of hyperkalemia within 90 days for each of the eight antihypertensive combination therapies.Results A total of 793 patients with hyperkalemia were matched to 3,788 normokalemic patients. In multivariable analysis, odds of developing hyperkalemia when being treated with BB + RASi + MRA was 2.58 (95% CI, 1.87–3.56) compared to RASi + thiazides (reference). Another significant association with other combinations that indicated a strong association with increased hyperkalemia was seen for the BB + RASi combination (OR, 1.55 [95% CI, 1.21-2.00]). Combinations including CCB + RASi (OR, 1.00 [95% CI, 0.76–1.32]) and CCB + RASi + thiazides (OR, 0.85 [95% CI, 0.54–1.34]) were not significantly associated with hyperkalemia.Conclusion Combinations of BB + RASi, with and without MRA were significantly associated with an increased risk of developing hyperkalemia within 90 days of initiating treatment.