Sacubitril/Valsartan: Neprilysin Inhibition 5 Years After PARADIGM-HF

Authors and Disclosures

Kieran F. Docherty, MBCHB^a,*, Muthiah Vaduganathan, MD, MPH^b,*, Scott D. Solomon, MD^b and John J.V. McMurray, MBCHB, MD<sup>a

a</sup>British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom; and the ^bBrigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts. *Drs. Docherty and Vaduganathan contributed equally to this work and are joint first authors. Dr. Vaduganathan is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH/NCATS Award UL 1TR002541); and serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Celladon, Gilead, GlaxoSmithKline, Ionis Pharmaceutics, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Novartis, Sanofi Pasteur, and Theracos; and has consulted for Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Corvia, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Pfizer, Takeda, and Theracos. Prof. McMurray's employer, Glasgow University, has been paid by Novartis (who manufacture sacubitril/valsartan) for his time spent as committee member for the trials listed (using sacubitril/valsartan), meetings related to these trials and other activities related to sacubitril/valsartan e.g., lectures, advisory boards and other meetings. Novartis has also paid his travel and accommodation for some of these meetings. These payments were made through a Consultancy with Glasgow University and he has not received personal payments in relation to these trials/this drug. The trials include PARADIGM-HF: co-PI; PARAGON-HF: co-PI; PERSPECTIVE, PARADISE-MI and UK HARP III Trial: executive/steering committees. Prof. McMurray and Dr. Docherty are conducting an investigator originated study funded by the British Heart Foundation (Project Grant no. PG/17/23/32850) using sacubitril/valsartan supplied by Novartis.

Address for Correspondence
Prof. John J.V. McMurray, Institute of Cardiovascular and Medical Sciences, BHF Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, United Kingdom. E-mail: john.mcmurray@glasgow.ac.uk.

Appendix

For supplemental tables, please see the online version of this paper.

Sidebar

Highlights

• In PARADIGM-HF, sacubitril/valsartan reduced morbidity and mortality compared to enalapril in patients with chronic HFrEF.

• A series of subsequent analyses of PARADIGM-HF have provided further insight into the benefits of sacubitril/valsartan compared to enalapril.

• Subsequent smaller mechanistic trials have highlighted the favorable effects of sacubitril/valsartan in attenuating adverse myocardial remodeling.

• Other trials have advanced potential pathways for therapeutic implementation (including during hospitalization for heart failure).

• Ongoing trials may provide evidence of new indications for sacubitril/valsartan.