Physicians' Academy for Cardiovascular Education

Early benefit on health status with ARNI treatment in HFrEF patients

Association Between Sacubitril/Valsartan Initiation and Health Status Outcomes in Heart Failure With Reduced Ejection Fraction

Literature - Khariton Y, Fonarow GC, Arnold SV et al.., - JACC: Heart Failure. 2019. DOI: 10.1016/j.jchf.2019.05.016

Introduction and methods

Health status in patients with heart failure with reduced ejection fraction (HFrEF) is a strong and independent predictor of CV morbidity and mortality [1-4] and optimizing health status is a primary treatment goal. Few therapeutic agents have, however, been demonstrated to improve quality of life (QoL) and reduce symptoms.

Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) treatment that was demonstrated to improve survival and lower hospitalization rates in HFrEF as compared with enalapril, in the PARADIGM-HF study. Moreover, less deterioration of health status was seen in ARNI-treated patients from baseline to 8 months [5]. A limitation of the PARADIGM-HF trial was that it did not assess health status before the run-in phase, thus early health status benefits of sacubitril/valsartan could not be evaluated. Moreover, the impact of ARNI treatment on patients’ health status in routine clinical practice is unknown.

This study therefore used data from the CHAMP-HF (Change the Management of Patients with Heart Failure) registry [6] to assess the association between treatment with sacubitril/valsartan and patient-reported health status. CHAMP-HF is a prospective, multicenter, observational registry of outpatients with HFrEF (EF ≤40%) that captures serial health status outcomes by means of the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). Change in KCCQ score was the primary outcome and the clinical significance of patient-level changes was defined as small (<5), moderate (5-10), large (10-20) or very large (>20 points) improvement.

Patients were allocated to ARNI therapy or not, depending on whether they began ARNI treatment at any time after enrollment. Patients were matched (1:2) on their pre-ARNI ACEi/ARB status (using ACEi/ARB in the preceding 2 weeks), and on a time-dependent propensity score and their most recent KCCQ-overall summary (OS) score. 508 of Patients who were newly prescribed ARNI were successfully matched with 1016 patients who had not begun ARNI therapy at the same point during follow-up. Of those initiating ARNI treatment, 267 (53%) had taken ACEi/ARB therapy and 241 (47%) had not in the 2 weeks preceding ARNI initiation.

Main results


Real-world data of the CHAMP-HF study shows that outpatients with chronic HFrEF starting treatment with sacubitril/valsartan experience early and robust improvements in disease-specific health status. Benefits were greatest in the physical limitation and QoL domains. The benefit of ARNI treatment was independent of prior treatment with ACEi/ARB.


Show references

Find this article online at JACC: Heart Failure

Share this page with your colleagues and friends: