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Managing Heart Failure With Reduced Ejection Fraction in Patients With Chronic Kidney Disease: A Case-Based Approach
1Associate Professor (Partner), Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Insights
Managing heart failure with reduced ejection fraction (HFrEF) in patients with chronic kidney disease (CKD) requires careful drug selection and dosing. Monitoring renal function and potassium is crucial when titrating standard HFrEF therapies in CKD patients.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Heart failure with reduced ejection fraction (HFrEF) frequently coexists with chronic kidney disease (CKD).
- CKD complicates the management of standard HFrEF pharmacotherapies due to altered drug pharmacokinetics and increased toxicity risk.
- Individualized dosing strategies considering renal function trends and drug-specific risks are essential.
Purpose of the Study:
- To review the challenges and strategies for optimizing guideline-directed medical therapy in HFrEF patients with concurrent CKD.
- To provide evidence-based recommendations for the use of renin-angiotensin system inhibitors, sacubitril/valsartan, beta-blockers, SGLT2 inhibitors, and MRAs in this population.
Main Methods:
- Literature review of current guidelines and clinical trials.
- Analysis of drug efficacy and safety profiles in patients with varying degrees of renal impairment.
- Synthesis of recommendations for drug initiation, titration, and monitoring.
Main Results:
- Renin-angiotensin system inhibitors can be used with close monitoring for renal function and hyperkalemia.
- Sacubitril/valsartan is contraindicated with an eGFR < 30 mL/min/1.73 m².
- Bisoprolol is the preferred beta-blocker, though dose titration is still necessary.
- SGLT2 inhibitors (dapagliflozin, empagliflozin) offer cardiovascular and renal benefits if eGFR meets specific thresholds.
- Mineralocorticoid receptor antagonists are recommended for eGFR ≥ 30 mL/min/1.73 m², starting at low doses and titrating cautiously.
Conclusions:
- Pharmacologic management of HFrEF in CKD requires a tailored approach, balancing efficacy with renal safety.
- Careful selection and titration of therapies, alongside vigilant monitoring, can improve outcomes for these complex patients.
- Specific drug classes have different thresholds for initiation and require distinct monitoring parameters in CKD.
Abstract:
Patients with heart failure with reduced ejection fraction (HFrEF) often have concurrent chronic kidney disease (CKD), which can make initiating and titrating the 4 standard pharmacologic therapies a challenge. Drug dosing is often based on a calculation of the patient's creatine clearance or estimated glomerular filtration rate (eGFR), but it should also incorporate the trend in their renal function over time and the risk of toxicity of the drug. The presence of CKD in a patient should not preclude the use of a renin-angiotensin system inhibitor, although patients should be monitored frequently for worsening renal function and hyperkalemia. Sacubitril/valsartan is not recommended in patients with an eGFR < 30 mL/min per 1.73 m2. Of the 3 ß-blockers recommended in the management of HFrEF, only bisoprolol may accumulate in patients with renal impairment; however, patients should still be titrated to the target dose (10 mg daily) or the maximally tolerated dose, depending on their clinical response. The sodium-glucose cotransporter 2 inhibitors are effective at reducing adverse cardiovascular and renal outcomes in patients with HFrEF and CKD (eGFR ≥ 25 mL/min per 1.73 m2 with dapagliflozin or ≥ 20 mL/min per 1.73 m2 with empagliflozin), although declining kidney function is a risk, due to the osmotic diuretic effect. Finally, mineralocorticoid receptor antagonist therapy should be considered in all patients with HFrEF and an eGFR ≥ 30 mL/min per 1.73 m2. The starting dose should be low (eg, 6.25-12.5 mg daily or 12.5 mg every other day) and can be uptitrated based on the patient's renal function and serum potassium.
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