Sacubitril/Valsartan and Ivabradine: Two Compounds for Heart Failure with Low Ejection Fraction (EFrEF), Acting by Innovative Mechanisms

Federico Cacciapuoti


The role of two new compounds - Sacubitril/valsartan and Ivabradine in treatment of systolic heart failure (HFrEF) was evaluated. Sacubitril/valsartan (also called as Entresto), together the remaining optimal medical therapy, antagonize HFrEF both strengthening the beneficial effects of natriuretic peptides (NP) and acting against angiotensin II by angiotensin receptor blocker (ARB), valsartan. PARADIGM-HF study has demonstrated that Sacubitril/valsartan is superior to angiotensin-converting-enzyme (ACE) alone in reducing the risks of death and hospitalization for HFrEF. On the contrary Ivabradine, a selective inhibitor of the “funny” channel current present in the sino-atrial node, acts against HFrEF inducing a reduction of heart rate in sinus rhythm patients. This reduction yields an improvement in stroke volume due to the increased of LV diastolic filling, improving the HFrEF symptoms. The results reported in the SHIFT Trial support the importance of heart rate reduction obtained with Ivabradine for improvement of clinical outcomes in HFrEF and confirm the important role of heart rate in the pathophysiology of this disorder. Two drugs act with two diverse and innovative mechanisms and, together the remaining optimal medical therapy, represent an effective improvement in HFrEF therapy.


Systolic heart failure; Ejection fraction; Sacubitril/valsartan (Entresto); Ivabradine

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