Author + information
- Received March 30, 2016
- Revision received May 2, 2016
- Accepted May 3, 2016
- Published online October 1, 2016.
- Scott D. Solomon, MDa,∗ (, )
- Brian Claggett, PhDa,
- Milton Packer, MDb,
- Akshay Desai, MDa,
- Michael R. Zile, MDc,
- Karl Swedberg, MDd,
- Jean Rouleau, MDe,
- Victor Shi, MDf,
- Martin Lefkowitz, MDf and
- John J.V. McMurray, MDg
- aCardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
- bBaylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas
- cMedical University of South Carolina and Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina
- dUniversity of Gothenburg, Gothenburg, Sweden
- eUniversity of Montreal, Montreal, Quebec, Canada
- fNovartis, East Hanover, New Jersey
- gUniversity of Glasgow, Glasgow, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Scott D. Solomon, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Objectives This study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability.
Background Despite the benefit of sacubitril/valsartan therapy shown in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, it has been suggested that switching from an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker should be delayed until occurrence of clinical decompensation.
Methods Outcomes were compared among patients who had prior hospitalization within 3 months of screening (n = 1,611 [19%]), between 3 and 6 months (n = 1,009 [12%]), between 6 and 12 months (n = 886 [11%]), >12 months (n = 1,746 [21%]), or who had never been hospitalized (n = 3,125 [37%]).
Results Twenty percent of patients without prior HF hospitalization experienced a primary endpoint of cardiovascular death or heart failure (HF) hospitalization during the course of the trial. Despite the increased risk associated with more recent hospitalization, the efficacy of sacubitril/valsartan therapy did not differ from that of enalapril according to the occurrence of or time from hospitalization for HF before screening, with respect to the primary endpoint or with respect to cardiovascular or all-cause mortality.
Conclusions Patients with recent HF decompensation requiring hospitalization were more likely to experience cardiovascular death or HF hospitalization than those who had never been hospitalized. Patients who were clinically stable, as shown by a remote HF hospitalization (>3 months prior to screening) or by lack of any prior HF hospitalization, were as likely to benefit from sacubitril/valsartan therapy as more recently hospitalized patients. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)
The PARADIGM-HF trial was funded by Novartis. Dr. Solomon is a consultant for and has received grants from Novartis. Dr. Packer has received consulting fees from Novartis. Dr. Desai is a consultant for Novartis, St. Jude Medical, Merck, and Relypsa; and has received travel support and grants from Novartis. Dr. Zile has received honoraria from Novartis for participation in the executive committee. Dr. Swedberg is an advisory board member and has received honoraria from Novartis. Dr. Rouleau is a consultant for Novartis. Dr. Shi is an employee of Novartis. Dr. Lefkowitz is an employee of Novartis. Dr. McMurray has received compensation while participating in the PARADIGM-HF study from Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 30, 2016.
- Revision received May 2, 2016.
- Accepted May 3, 2016.
- 2016 American College of Cardiology Foundation