Hospitalization Rates in Patients with Heart Failure and Reduced Ejection Fraction Initiating Sacubitril/Valsartan or Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers: A Retrospective Cohort Study

Abstract

Introduction: The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (SAC/VAL) has shown benefit in patients with symptomatic heart failure (HF), including those naïve to renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and is considered the preferred RAASi for chronic HF. Real-world data on ARNI, specifically in RAASi-naïve patients, are limited. This study compared real-world outcomes of ARNI (SAC/VAL) vs. angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy in RAASi-naïve patients with HF and reduced ejection fraction (HFrEF).

Methods: This retrospective cohort study included de-identified data on RAASi-naïve patients with HFrEF (left ventricular ejection fraction ≤ 40%) who had newly initiated SAC/VAL or ACEi/ARB between July 1, 2015, and March 31, 2019, from the Optum® Electronic Health Records database in the US. New SAC/VAL users were propensity score matched 1:2 with new ACEi/ARB users by pre-selected characteristics. One-year post-index rates of all-cause, HF, and cardiovascular hospitalizations and the composite of HF hospitalization or emergency room (ER) visits were measured using negative binomial regression. Time to first all-cause hospitalization, HF hospitalization, and composite of HF hospitalization or ER visits was measured using a subdistribution hazards model.

Results: The matched sample included 3059 new SAC/VAL and 6118 new ACEi/ARB users. Rates of all-cause hospitalization and composite of HF hospitalization or ER visits were significantly lower with SAC/VAL compared with ACEi/ARB (incidence rate ratio [95% confidence interval]: 0.87 [0.81-0.93] and 0.87 [0.81-0.94], respectively), whereas rates of HF hospitalizations and cardiovascular hospitalizations were similar (1.00 [0.91-1.11] and 0.94 [0.87-1.02], respectively). Time-to-event analyses also showed a similar trend.

Conclusions: In real-world clinical practice, RAASi-naïve patients with HFrEF initiating SAC/VAL were less likely to be hospitalized than those initiating ACEi/ARB, suggesting a potential for a reduced clinical and economic burden in these patients.

Keywords: Angiotensin receptor blocker; Angiotensin receptor neprilysin inhibitor; Angiotensin-converting enzyme inhibitor; Heart failure; Sacubitril/valsartan.

Fig. 1

Study design. SAC/VAL sacubitril/valsartan, ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker

Fig. 2

Patient selection. *Criteria used as a proxy for the continuous enrollment in the Optum EHR database as this information was not directly available. ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, CM Clinical Modification, EHR electronic health record, HF heart failure, ICD International Classification of Diseases, IDN Integrated Delivery Network, LVEF left ventricular ejection fraction, SAC/VAL sacubitril/valsartan

Fig. 3

Comparison of rate of events between new SAC/VAL users and new ACEi/ARB users. ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, CI confidence interval, CV cardiovascular, ER emergency room, HF heart failure, IRR incidence rate ratio, PY patient-year, SAC/VAL sacubitril/valsartan

Fig. 4

Comparison of time to event between new SAC/VAL users and new ACEi/ARB users. ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, CI confidence interval, ER emergency room, HF heart failure, HR hazard ratio, SAC/VAL sacubitril/valsartan