Heart failure with reduced ejection fraction (HFrEF) is a significant health issue, with sacubitril/valsartan (an angiotensin receptor neprilysin inhibitor) improving outcomes but potentially causing hyperkalemia due to aldosterone suppression and interactions with other therapies. This study evaluated potassium levels and hyperkalemia prevalence in HFrEF patients post-initiation, comparing pre- and post-treatment rates in a real-world Saudi cohort to inform monitoring strategies.
A retrospective cohort study at King Abdulaziz Cardiac Center, Riyadh, included 238 HFrEF patients starting sacubitril/valsartan (2016-2021). Data from electronic medical records encompassed demographics, comorbidities (e.g., diabetes, hypertension, CKD), concomitant medications (e.g., spironolactone, beta-blockers), and serum potassium at baseline (n=233) and follow-up intervals: 0-3 months (n=225), 3-6 months (n=171), and 6-12 months (n=176). Hyperkalemia was defined at thresholds >5.0, >5.5, and >6.0 mmol/L. Analyses used medians/IQRs for non-normal data, McNemar’s test for paired hyperkalemia changes, and 95% CIs. A sensitivity analysis focused on paired baseline/0-3 month data (n=220). No imputation was performed; complete-case analyses were used.
Median age was 58 years (IQR 48-69); 75.2% male; common comorbidities included diabetes (71.8%) and hypertension (70.6%); 77.7% used spironolactone. Baseline median potassium was 4.4 mmol/L (IQR 4.1-4.7). Post-initiation, it rose to 5.0 mmol/L (IQR 4.6-5.4) at 0-3 months. Hyperkalemia (>5.0 mmol/L) prevalence increased from 8.2% (95% CI: 5.3-12.4) baseline to 44.4% (95% CI: 38.1-51.0) at 0-3 months, 26.9% (95% CI: 20.8-34.0) at 3-6 months, and 33.0% (95% CI: 26.4-40.2) at 6-12 months (McNemar p<0.0001 for all vs. baseline). Moderate (>5.5 mmol/L) and severe (>6.0 mmol/L) rates at 0-3 months were 17.3% and 4.0%. Discontinuation occurred in 7.1%, with 1.3% due to hyperkalemia. Sensitivity analysis confirmed the rise (7.3% to 44.1%; p<0.0001).
Sacubitril/valsartan initiation significantly increases early mild hyperkalemia in HFrEF patients, particularly within 3 months, but severe cases and discontinuations are rare, aligning with trials like PARADIGM-HF. Structured early monitoring is essential, especially for CKD/MRA users. Limitations include retrospective design, missing data, and lack of controls/outcomes linkage; prospective multicenter studies are recommended.
