Hyperkalemia in Heart Failure with Reduced Ejection Fraction Patients Treated with Sacubitril/Valsartan: Experience from a Tertiary Cardiac Center in Riyadh, Saudi Arabia

<b>Background/Objectives</b>: Heart failure with reduced ejection fraction (HFrEF) remains a major global health burden. Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), improves outcomes in HFrEF but may cause hyperkalemia. <b>Methods</b>: A single-center retrospective cohort study was conducted at King Abdulaziz Cardiac Center, Riyadh, including 238 HFrEF patients initiated on sacubitril/valsartan (2016-2021). Potassium levels were assessed pre-initiation and at 0-3, 3-6, and 6-12 months post-initiation. Hyperkalemia was analyzed at thresholds >5.0, >5.5, and >6.0 mmol/L. <b>Results</b>: Median age was 58 years (IQR 48-69); 75.2% were male. Hyperkalemia >5.0 mmol/L occurred in 44.4% (95% CI: 38.1-51.0) within three months post-initiation versus 8.2% (95% CI: 5.3-12.4) pre-initiation. Only 17.3% exceeded 5.5 mmol/L. Treatment discontinuation occurred in 7.1% of patients, with 1.3% stopping due to clinically significant hyperkalemia. McNemar's test confirmed a significant increase in prevalence across time points (<i>p</i> < 0.0001). <b>Conclusions</b>: Despite increased hyperkalemia incidence, discontinuation rates were low, consistent with prior trials (PARADIGM-HF, PARAGON-HF). Sacubitril/valsartan remains an effective and generally safe therapy for HFrEF, with hyperkalemia manageable through monitoring. Limitations include missing potassium data, potential confounding factors, and the lack of a control group; future prospective studies with regular electrolyte monitoring are recommended.