Patients with mild 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.
Dr. Feldman went on to note that "doctors are prescribing these drugs without knowledge of these theoretical risks."
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, a peptide that can accumulate in the brain, where it contributes to Alzheimer's disease, as well as in the eye, where it is implicated in macular degeneration. The balance between the production and clearance of amyloid beta is crucial to the pathogenesis of Alzheimer's disease and is suspected to influence the development of macular degeneration. In animal models, blocking neprilysin disturbs that balance and exacerbates the development of Alzheimer's pathology.