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Valsartan/Sacubitril for Heart Failure Reconciling Disparities Between Preclinical and Clinical Investigations

Arthur M. Feldman, MD, PhD1; Julia A. Haller, MD2,3; Steven T. DeKosky, MD4
[+] Author Affiliations
1Departments of Medicine and Physiology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania
2Wills Eye Institute, Philadelphia, Pennsylvania
3Thomas Jefferson University, Philadelphia, Pennsylvania
4Department of Neurology, McKnight Brain Institute, University of Florida College of Medicine, Gainesville
JAMA. 2016;315(1):25-26. doi:10.1001/jama.2015.17632.
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This Viewpoint discusses the importantance of developing effective mechanisms for reconciling differences that emerge when information accrual from genetic animal models outpace the data collection from patients enrolled in clinical trials.

Valsartan/sacubitril (Entresto, Novartis) is a combination of the neprilysin inhibitor sacubitril and the angiotensin receptor antagonist valsartan. In July 2015, the US Food and Drug Administration (FDA) approved valsartan/sacubitril through the fast-track pathway for the treatment of patients with New York Heart Association class II through IV heart failure symptoms and a reduced ejection fraction. The approval was based on the results of a single phase 3 clinical trial (PARADIGM-HF)1 that included 8400 patients. In this trial, valsartan/sacubitril was associated with a 20% (hazard ratio, 0.80) decrease in the primary end point of death from cardiovascular cause or first hospitalization for heart failure (from 26.5% to 21.8%), when compared with the angiotensin-converting inhibitor enalapril, and a 16% (hazard ratio, 0.84) reduction in all-cause mortality (from 19.8% to 17.0%). However, recent translational science studies involving the central nervous system and the eye suggest that other effects of valsartan/sacubitril might influence its use in some patients.


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