Sacubitril/valsartan therapeutic strategy in HFpEF: Clinical insights and perspectives

• Published in: International journal of cardiology Vol. 281; pp. 158 - 165
• Main Authors: Gori, Mauro, D'Elia, Emilia, Senni, Michele
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2019
• Subjects: Aminobutyrates - administration & dosage; Angiotensin Receptor Antagonists - administration & dosage; Animals; Drug Combinations; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart failure with preserved ejection fraction; Humans; Neprilysin inhibition; Randomized Controlled Trials as Topic - methods; Sacubitril/valsartan; Stroke Volume - drug effects; Stroke Volume - physiology; Tetrazoles - administration & dosage; Heart failure with preserved ejection fraction; Neprilysin inhibition; Sacubitril/valsartan
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2018.06.060

Sacubitril/valsartan represents the first of a new class of drugs able to act as a neprilysin inhibitor and as an angiotensin receptor blocker. This double inhibition has the advantage of concomitantly blocking a pro-fibrotic/pro-hypertrophic mechanism (angiotensin receptor blocker component) while stimulating an anti-fibrotic/anti-hypertrophic mechanism (neprilysin inhibitor component). Furthermore, the novel drug has natriuretic and diuretic properties, better preserves renal function, provides better blood pressure control as compared to renin angiotensin system inhibitors, and improves ventricular-arterial coupling. Consequently, sacubitril/valsartan provides greater target organ protection than angiotensin receptor blocker therapy alone, including cardiac, vascular, and renal protection. Up to now, this drug does not have an indication in patients with heart failure with preserved ejection fraction (HFpEF). However, its complex mechanism of action and previous experimental and clinical data seem to suggest its possible success in HFpEF. In this review we highlight and discuss the rationale, clinical insights, and perspectives behind the use of sacubitril/valsartan in HFpEF, specifically referring to its possible efficacy in pathophysiologic mechanisms, such as myocardial hypertrophy, fibrosis, and ischemia, renal dysfunction, impaired ventricular-arterial coupling, which are all tightly related to elevated left ventricular end diastolic pressure, a common hallmark for this multifaceted syndrome. •Trials of conventional heart failure medications have been inconclusive in HFpEF.•LCZ696 is a novel drugs able to act as a neprilysin inhibitor and as an angiotensin receptor blocker.•The PARAMOUNT-HF trial gave promising results on the effectiveness of LCZ696 in HFpEF.