Author + information
- Kieran F. Docherty, MBChBa,∗,
- Muthiah Vaduganathan, MD, MPHb,∗,
- Scott D. Solomon, MDb and
- John J.V. McMurray, MBChB, MDa,∗ ()
- aBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
- bBrigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts
- ↵∗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.
• 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.
Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms among patients with chronic heart failure with reduced ejection fraction compared to enalapril, the gold standard angiotensin-converting enzyme inhibitor. In the 5 years since the publication of the results of PARADIGM-HF, further insight has been gained into integrating a neprilysin inhibitor into a comprehensive multidrug regimen, including a renin-angiotensin aldosterone system (RAS) blocker. This paper reviews the current understanding of the effects of sacubitril/valsartan and highlights expected developments over the next 5 years, including potential new indications for use. Additionally, a practical, evidence-based approach is provided to the clinical integration of sacubitril/valsartan among patients with heart failure with reduced ejection fraction.
↵∗ 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.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failure author instructions page.
- Received May 21, 2019.
- Revision received June 10, 2020.
- Accepted June 11, 2020.
- Central Illustration
- How Does Neprilysin Inhibition Work?
- Clinical Benefits of Sacubitril/Valsartan Versus RAS Blockade Alone
- Safety of Sacubitril/Valsartan
- Sacubitril/Valsartan Across The HF Spectrum
- Practical Considerations With Sacubitril/Valsartan