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Abstract: TH-PO1108

A Cause for Concern: RAAS Inhibitors Are Associated with Significant Risk of Hyperkalemia in Patients with Chronic Heart Failure: A Meta-Analysis

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 704 Fluid, Electrolyte, Acid-Base Disorders


  • Jain, Ankur, University of Florida, Gainesville, Florida, United States
  • Koratala, Abhilash, University of Florida, Gainesville, Florida, United States
  • Nasser, Hesham, University of Florida, Gainesville, Florida, United States
  • Kazory, Amir, University of Florida, Gainesville, Florida, United States

Inhibitors of renin-angiotensin-aldosterone system (RAAS) are widely used in patients with chronic heart failure (HF). We previously reported that the impact of angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) on renal function is distinct from that of downstream blockers of the RAAS (i.e. mineralocorticoid receptor antagonists [MRA]). In this study, we sought to evaluate the effect of these agents on the incidence of hyperkalemia in HF.


Articles cited in PubMed, EMBASE, and Cochrane database from 1987 to 2017 using key words: “heart failure”, “angiotensin-converting enzyme”, “angiotensin receptor blocker”, and “mineralocorticoid receptor antagonist” were searched and those randomized controlled trials (RCTs) that addressed the impact of RAAS inhibition in HF were identified. Hyperkalemia, defined as serum potassium level >5.5 mmol/L, was considered the primary endpoint. A meta-analysis was performed. Mantel-Haenszel random-effects model was used to calculate risk ratios (RRs) with 95% confidence intervals (CIs).


A total of 3389 studies were selected after extensive database search. After excluding duplicate and non-randomized trials, 14 RCTs with 29,433 participants were found eligible for analysis. Compared to placebo, ACE-I/ARB significantly increased the risk of hyperkalemia (RR 2.31 CI 1.77-3.02, p≤0.01). Addition of MRA to ACE-I/ARB further increased the risk (RR 2.19 CI 1.51-3.16, p≤0.01). When evaluated for severe hyperkalemia (i.e. serum potassium levels > 6 mmol/L), ACE-I/ARB increased the risk compared to placebo (RR 1.59, CI 1.13-2.25, p=0.01), and addition of MRA to ACE-I/ARB further increased it (RR 1.63 CI 1.13-2.35, p=0.01).


In patients with HF, ACE/ARB therapy increases the risk of hyperkalemia by more than two folds and downstream addition of MRA increases the risk further. RAAS inhibitors have been shown to improve outcomes including mortality in this patient population. Future studies are needed to evaluate therapeutic strategies (e.g. newer potassium binders) for prevention of hyperkalemia to avoid underutilization of RAAS inhibition.