Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease

Chronic kidney disease (CKD), defined by a reduced estimated glomerular filtration rate (eGFR) is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF). CKD is a significant risk factor for worse cardiovascular outcomes and is associated with more severe heart failure. Furthermore, when present, CKD often influences the decision to start, uptitrate, or discontinue possible life-saving HFrEF therapies. Historically pivotal HFrEF trials have excluded heart failure patients with CKD stage 4 and 5 (eGFR <30 mL/min/1.73 m2. Therefore, information on the efficacy and safety of HFrEF therapies in these patients is limited. More recent HFrEF trials with novel classes of drugs have included patients with more severe CKD. In this review, we show that for all-cause mortality and the combined endpoint of cardiovascular death or heart failure hospitalization, most HFrEF drug classes are safe and effective up to CKD stage 3B (eGFR minimum 30 mL/min/1.73 m2). In HF patients with CKD stage 4 (eGFR 15 – 29 ml/min/1.73m2), evidence is available of efficacy and tolerability of sodium glucose cotransporter 2 inhibitors, and to a lesser extent in angiotensin-converting enzyme inhibitors, vericiguat, digoxin and omecamtiv mecarbil, regarding the endpoint of cardiovascular death and heart failure hospitalization. In CKD stage 5 (eGFR < 15 mL/min/1.73 m2 or dialysis) data is lacking for both endpoints. After initiation of several HFrEF drug classes (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/mineralocorticoid receptor antagonists/angiotensin receptor blocker neprilysin inhibitors/sodium glucose cotransporter 2 inhibitors), an initial decline in eGFR is frequently observed. However, renal function often stabilizes over time, and the drugs maintain their efficacy. In the context of a stable or improving clinical condition, a decline in eGFR should therefore not be a cause for concern and should not lead to discontinuation of life-saving HFrEF therapies.