Promising New Therapies in Heart Failure: Ivabradine and the Neprilysin Inhibitors

Abstract

Current guideline-directed medical therapy for heart failure (HF) is a triumph of translation medicine. An understanding of neurohormonal activation, translated into medications to block these maladaptive systems, has culminated in improved quality of life and survival for patients with HF. The most effective drug therapies for chronic systolic HF are those that inhibit the activity of the sympathetic nervous system (SNS) and renin angiotensin aldosterone system (RAAS). These agents include the beta-blockers to inhibit SNS activity and the angiotensinconverting enzyme inhibitors (Aces), angiotensin II type 1 receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRA) to act on the RAAS pathway. Two new HF medications have recently been approved and represent a deepened understanding of neurohormonal mechanisms in HF. The first is ivabradine, which inhibits the funny current of the sinoatrial node and lowers heart rate without reducing contractility. In patients already on maximally tolerated beta-blocker dosages, ivabradine reduces the risk of HF hospitalization. The second medication is sacubitril combined with valsartan, which takes advantage of the natriuretic peptide system and other endogenous vasoactive peptides. Sacubitril, a neprilysin inhibitor, increases vasoactive peptide levels resulting in beneficial effects in HF. The angiotensin receptorneprilysin inhibitor combination sacubitril/valsartan is superior enalapril in reducing death and HF hospitalizations. This review article provides an overview of guideline-directed medical therapy in HF. It highlights the mechanisms of these two new HF agents and their pivotal clinical trials and offers practical advice for prescribing these medications to HF patients.