• Scott D Solomon, Brian Claggett, Milton Packer, Akshay Desai, Michael R Zile, Karl Swedberg, Jean Rouleau, Victor Shi, Martin Lefkowitz, and McMurrayJohn J VJJVUniversity of Glasgow, Glasgow, United Kingdom..
• Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: ssolomon@rics.bwh.harvard.edu.
• JACC Heart Fail. 2016 Oct 1; 4 (10): 816-822.

ObjectivesThis study assessed whether the benefit of sacubtril/valsartan therapy varied with clinical stability.BackgroundDespite 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.MethodsOutcomes 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%]).ResultsTwenty 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.ConclusionsPatients 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).Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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