Efficacy of Sacubitril/Valsartan Relative toa Prior Decompensation

Fro Ba Ve Mo Kin Dr an ex con com rel Ma 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 1⁄4 1,611 [19%]), between 3 and 6 months (n 1⁄4 1,009 [12%]), between 6 and 12 months (n 1⁄4 886 [11%]), >12 months (n 1⁄4 1,746 [21%]), or who had never been hospitalized (n 1⁄4 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) (J Am Coll Cardiol HF 2016;-:-–-) © 2016 by the American College of Cardiology Foundation. T he angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) (1) reduced both death and heart failure (HF) hospitalizations in patients with New York Heart Association (NYHA) functional classes II to IV HF and ejection m the Cardiovascular Division, Brigham and Women’s Hospital, Boston, ylor University Medical Center, Dallas, Texas; Medical University of So terans Affairs Medical Center, Charleston, South Carolina; University o ntreal, Montreal, Quebec, Canada; Novartis, East Hanover, New Jersey gdom. The PARADIGM-HF trial was funded by Novartis. Dr. Solomon is a c . Packer has received consulting fees from Novartis. Dr. Desai is a consultan d has received travel support and grants from Novartis. Dr. Zile has recei ecutive committee. Dr. Swedberg is an advisory board member and has sultant for Novartis. Dr. Shi is an employee of Novartis. Dr. Lefkowitz is a pensation while participating in the PARADIGM-HF study from Novartis ationships relevant to the contents of this paper to disclose. nuscript received March 30, 2016; revised manuscript received May 2, 20 fraction compared with enalapril in the PARADIGMHF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial (2). The benefits of sacubitril/valsartan therapy were consistent across Massachusetts; Baylor Heart and Vascular Institute, uth Carolina and Ralph H. Johnson Department of f Gothenburg, Gothenburg, Sweden; University of ; and the University of Glasgow, Glasgow, United onsultant for and has received grants from Novartis. t for Novartis, St. Jude Medical, Merck, and Relypsa; ved honoraria from Novartis for participation in the received honoraria from Novartis. Dr. Rouleau is a n employee of Novartis. Dr. McMurray has received . All other authors have reported that they have no 16, accepted May 3, 2016. ABBR EV I A T I ON S