Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in CKD: A Population-Based Cohort Study
Abstract
RATIONALE & OBJECTIVE
Renin-Angiotensin-Aldosterone system inhibitors (RAASi) are evidence-based therapies that slow the progression of Chronic Kidney Disease (CKD) but can cause hyperkalemia. We aimed to evaluate the association of discontinuing RAASi's after an episode of hyperkalemia and clinical outcomes in patients with CKD.
STUDY DESIGN
Retrospective cohort study.
SETTING AND PARTICIPANTS
Adults in Manitoba (7,200) and Ontario, Canada (n=71,290) with an episode of de novo RAASi-related hyperkalemia (serum potassium ≥ 5.5 mmol/L) and CKD.
EXPOSURE
RAASi prescription.
OUTCOMES
The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, fatal and non-fatal CV events, dialysis initiation and a negative control outcome (cataract surgery).
ANALYTICAL APPROACH
Cox proportional hazards models examined the association of RAASi continuation (vs. discontinuation) and outcomes using intention to treat approach. Sensitivity analyses included time-dependent, dose-dependent, and propensity matched analyses.
RESULTS
The mean potassium and mean eGFR were 5.8 mEq/L and 41 ml/min/1.73m2 in Manitoba and 5.7 mEq/L and 41 ml/min/1.73m2 in Ontario. RAASi discontinuation was associated with a higher risk of all-cause mortality [hazard ratio (HR) 1.32, 95% CI: 1.22-1.41 in Manitoba, and HR: 1.47, 95% CI: 1.41-1.52 in Ontario] and cardiovascular mortality [HR: 1.28, 95% CI: 1.13-1.44 in Manitoba, and HR: 1.32, 95% CI: 1.25-1.39 in Ontario]. RAASi…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 71,290 participants or records.
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