Elsevier

JACC: Heart Failure

Volume 8, Issue 1, January 2020, Pages 43-54
JACC: Heart Failure

Clinical Research
Comparative Effectiveness of Sacubitril-Valsartan Versus ACE/ARB Therapy in Heart Failure With Reduced Ejection Fraction

https://doi.org/10.1016/j.jchf.2019.08.003Get rights and content
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Abstract

Objectives

This paper aims to compare the effectiveness of sacubitril-valsartan and angiotensin-converting enzyme inhibitor (ACE)/angiotensin receptor blocker (ARB) in systolic heart failure (HF).

Background

Sacubitril-valsartan reduced risks of death and hospitalization for HF versus enalapril in ambulatory patients with HF and reduced ejection fraction in the PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor with Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) trial. However, the comparative effectiveness of sacubitril-valsartan and ACE/ARB in patients treated in routine clinical practice is unclear.

Methods

We identified patients with systolic HF in a U.S. administrative claims database treated with sacubitril-valsartan or ACE/ARB from July 1, 2015, to February 2, 2018. One-to-one propensity score matching was used to balance patients on 29 clinical variables. Cox models were used to compare outcomes between treatment groups.

Results

A total of 7,893 matched pairs were included; mean (SD) follow-up was 6.3 (5.4) months. Sacubitril-valsartan was associated with lower risks of all-cause mortality or all-cause hospitalization (hazard ratio [HR]: 0.86, 95% confidence interval (CI): 0.81 to 0.91; p < 0.001), all-cause mortality (HR: 0.80, 95% CI: 0.66 to 0.97; p = 0.027), and all-cause hospitalization (HR: 0.86, 95% CI: 0.80 to 0.91; p < 0.001), but not HF hospitalization (HR: 1.07, 95% CI: 0.96 to 1.19; p = 0.26). A lower risk of the primary outcome with sacubitril-valsartan was observed in white patients (HR: 0.83, 95% CI: 0.76 to 0.90) but not black patients (21% of population, HR: 1.00, 95% CI: 0.88 to 1.15; interaction p = 0.032). No statistically significant differences in treatment response by sex or age were observed.

Conclusions

Sacubitril-valsartan was associated with lower risks of death and hospitalization compared with ACE/ARB in a heterogeneous cohort of patients with systolic HF. However, our finding that outcomes with sacubitril-valsartan and ACE/ARBs were similar in black patients warrants further evaluation.

Key Words

heart failure
hospitalization
medication
mortality
sacubitril-valsartan

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme inhibitor
ARB
angiotensin receptor blocker
CI
confidence interval
HF
heart failure
HFrEF
heart failure with reduced ejection fraction
HR
hazard ratio
ICD
implantable cardioverter-defibrillator

Cited by (0)

Dr. Shah has received grants from Centers for Medicare & Medicaid Services (CMS)/Center for Medicare & Medicaid Innovation (CMMI), Food and Drug Administration (FDA), Agency for Healthcare Research and Quality (AHRQ), National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), and National Science Foundation (NSF). Dr. S.J. Sangaralingham has received grants from the NIH and the FDA. Dr. Dunlay has received grants from the NIH and from the Patient Centered Outcomes Research Institute to develop a Clinical Data Research Network. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.