Sacubitril/valsartan Eligibility and Outcomes in the ESC-EORP-HFA Heart Failure Long-Term Registry: Bridging Between European Medicines Agency/Food and Drug Administration Label, the PARADIGM-HF Trial, ESC Guidelines, and Real World

Eur J Heart Fail. 2019 Nov;21(11):1383-1397. doi: 10.1002/ejhf.1532. Epub 2019 Jun 18.

Abstract

Aims: To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM-HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes.

Methods and results: Outpatients with HFrEF in the ESC-EORP-HFA Long-Term Heart Failure (HF-LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM-HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM-HF and guideline criteria, respectively. Absent PARADIGM-HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub-optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub-optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM-HF and guidelines. One-year heart failure hospitalization was higher (12% and 17% vs. 12%) and all-cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM-HF.

Conclusions: Among outpatients with HFrEF in the ESC-EORP-HFA HF-LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM-HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM-HF enalapril group.

Keywords: Angiotensin receptor-neprilysin inhibitor; Eligibility; LCZ696; Prognosis; Registry; Sacubitril/valsartan.

Publication types

  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Heart Failure*
  • Humans
  • Neprilysin
  • Registries
  • Stroke Volume
  • Tetrazoles
  • United States
  • United States Food and Drug Administration
  • Valsartan

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Tetrazoles
  • Valsartan
  • Neprilysin
  • sacubitril-valsartan