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New drug for heart failure: Entresto by Novartis

“Patients with heart failure stand to benefit from a new drug that can halt the progression of their disease and reduce their risk of cardiovascular–related death. But the drug — a tablet that combines the agents valsartan and sacubitril, sold under the trade name Entresto by drugmaker Novartis — may be too good to be true, according to Arthur M. Feldman, MD, PhD, Executive Dean of the Lewis Katz School of Medicine at Temple University (LKSOM), Chief Academic Officer of the Temple University Health System, and Laura H. Carnell Professor of Medicine at LKSOM. In an article published online December 7th in the Journal of the American Medical Association, Dr. Feldman and colleagues at Thomas Jefferson University and the University of Florida warn that valsartan/sacubitril could theoretically increase patients’ risk of Alzheimer’s disease and macular degeneration, a blinding condition affecting the retina of the eye. The article raises these concerns about the drug, which was approved by the U.S. Food and Drug Administration in July 2015. “Basic science data has caused us to speculate that off–target effects of valsartan/sacubitril may cause an exacerbation of Alzheimer’s disease and could also exacerbate the course of macular degeneration,” Dr. Feldman explained. Valsartan/sacubitril works by inhibiting an enzyme known as neprilysin, which normally plays a critical role in breaking down a wide array of peptides in cells. Among those substances are the so–called natriuretic peptides, which function in regulating scarring and cell growth in the heart when neprilysin is blocked. Because of those activities, valsartan/sacubitril can delay the progression of heart failure in some patients. Neprilysin, however, also normally degrades amyloid beta. In heart failure patients the blood–brain barrier frequently is compromised by hypertension and other vascular conditions, allowing drugs to enter the central nervous system.” (Journal of the American Medical Association, 2015)

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