RESEARCH LETTER
Scope of Sacubitril/Valsartan Eligibility After Heart Failure Hospitalization Findings From the GWTG-HF Registry (Get With The Guidelines-Heart Failure)
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Circulation. 2017;135:2077–2080. DOI: 10.1161/CIRCULATIONAHA.117.027773
Kishan S. Parikh, MD Steven J. Lippmann, PhD Melissa Greiner, MS Paul A. Heidenreich, MD, MS Clyde W. Yancy, MD, MSc Gregg C. Fonarow, MD Adrian F. Hernandez, MD, MHS
Correspondence to: Adrian F. Hernandez, MD, MHS, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715. E-mail
[email protected] Key Words: drugs ◼ heart failure © 2017 American Heart Association, Inc.
May 23, 2017
2077
CORRESPONDENCE
acubitril/valsartan was compared to enalapril in the PARADIGM-HF trial (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure [HF]), which was stopped early after an observed 20% reduction in the composite end point of cardiovascular death or HF hospitalization.1 The US Food and Drug Administration (FDA) approved sacubitril/ valsartan for patients with HF with reduced ejection fraction (HFrEF) in July 2015. However, FDA labeling is broader than trial entry criteria, and the scope of potential sacubitril/valsartan use in HFrEF is not well understood. We used the GWTG-HF registry (Get With The Guidelines-Heart Failure) to characterize patients’ eligibility and potential barriers for sacubitril/valsartan initiation according to criteria set forth in FDA labeling and PARADIGM-HF. The GWTG-HF registry was started in 2005 by the American Heart Association to improve adherence to quality of care guidelines for patients hospitalized for HF. Patients were eligible for inclusion in the registry if they were admitted for worsening HF or developed significant HF symptoms during a hospitalization.2 We included GWTG-HF registry participants ≥18 years of age hospitalized with HFrEF (EF ≤40%) between January 1, 2011, and December 31, 2013. Patients were excluded if they had in-hospital death or any missing information for variables needed to determine PARADIGM-HF eligibility. To assess clinical outcomes after discharge, participants who were ≥65 years of age with fee-for-service Medicare coverage were linked to Medicare denominator and inpatient claims files. We divided patients into 3 groups: FDA-excluded (not meeting FDA labeling), PARADIGM-HF-excluded (meeting FDA but not PARADIGM-HF criteria), and PARADIGM-HFlike (meeting PARADIGM-HF criteria). FDA labeling requires HFrEF, potassium ≤5.2 mmol/L, and no contraindication or intolerance to ACEI/angiotensin-receptor blocker (ARB). To incorporate real-world considerations, we also required patients to have discharge SBP ≥90 mm Hg because of concern for hypotension with sacubitril/valsartan. The PARADIGM-HF-like group met the following additional criteria: EF ≤35%; BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL (or, if hospitalized for HF within 6 months, BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL); on ACEI/ARB and β-blocker at discharge; discharge SBP ≥100 mm Hg; and estimated glomerular filtration rate ≥30 mL/min/1.73 m2. PARADIGM-HF criteria were modified based on GWTG-HF data availability in 2 instances: (1) natriuretic peptide cutoffs were determined with a 12-month window of previous HF hospitalizations in PARADIGM-HF; and (2) a 2-week run-in period with enalapril 20 mg daily in PARADIGM-HF (no ACEI discharge dose in GWTG-HF). For the primary analysis, we made group comparisons for baseline, in-hospital, and discharge characteristics; for the Medicare-linked analysis, we compared survival and HF hospitalization outcomes at 30 days and 1 year after discharge. The Institutional Review Board of the Duke University Health System approved this study. Among 28 932 hospitalizations of HFrEF patients, 20 083 (69%) were for patients meeting FDA labeling (Table). The stricter PARADIGM-HF criteria limited eligibility to
Parikh et al
Table. Characteristics and Outcomes, by Sacubitril/Valsartan Eligibility FDAExcluded
PARADIGMHF-Excluded
PARADIGMHF-Like
8849
9065
11 018
Age, mean±SD, y
71.8±14.2
69.3±15.1
66.8±15.4
