Heart failure (HF) remains a significant public health burden, requiring guideline-directed medical therapies—particularly renin-angiotensin-aldosterone system (RAAS) inhibitors—to improve survival. However, these life-saving medications frequently cause hyperkalemia (elevated potassium levels), a condition linked to arrhythmias, hospitalization, and mortality. In clinical practice, hyperkalemia often prompts a gradual dose reduction or discontinuation of RAAS inhibitors. Despite available potassium-management strategies, these therapies are rarely reintroduced once stopped, potentially compromising patient outcomes.
This population-based cohort study assessed the incidence of hyperkalemia in patients with chronic HF receiving RAAS inhibitors and the clinical impact of subsequent treatment modifications. Specifically, it compared outcomes associated with discontinuing or gradually reducing therapy versus continuing treatment.
In a cohort of 67,557 patients, RAAS inhibitor–associated hyperkalemia was common, with an incidence of 17 episodes per 100 treatment-years. Following a hyperkalemia episode, clinicians frequently reduced or discontinued therapy. Critically, these modifications were associated with a significant increase in adverse events, confirming the protective value of RAAS inhibitors. Furthermore, dose reduction or discontinuation did not significantly lower the risk of recurrent hyperkalemia compared to maintaining therapy. This finding underscores the need to look beyond cardiovascular disease and investigate other factors driving hyperkalemia.
Ultimately, this study highlights a critical paradox: while hyperkalemia events often drive the decision to reduce or stop RAAS inhibitors, this discontinuation is associated with higher rates of mortality and cardiovascular events. Consequently, strategies that allow patients to maintain therapy—such as the use of potassium binders—may significantly improve outcomes, even after high-potassium episodes. While monitoring remains essential, clinicians should exercise caution before discontinuing RAAS inhibitor therapy.
This study was led by CVC trainee Aanchel Gupta, BA, MD, under the supervision of Justin Ezekowitz, MBBCh, MSc. It was conducted in collaboration with Sunjidatul Islam, MBBS, MSc; Douglas Dover, PhD; Padma Kaul, PhD; and Finlay McAlister, MD, MSc.
