Be part of the knowledge.

We’re glad to see you’re enjoying ReachMD…
but how about a more personalized experience?

Register for free

Early benefit on health status with ARNI treatment in HFrEF patients
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

  • The average KCCQ-OS score at enrollment in the CHAMP-HF study was 63.6 ± 23.7, which corresponds to New York Heart Association (NYHA) functional class II.
  • From the last pre-match to the first post-match health status assessment, during a median of 57 days (IQR: 32-104), ARNI patients experienced an average 5.3 ± 18.6-point improvement in the KCCQ-OS, compared to 2.5 ± 17.4 points in no-ARNI patients (adjusted group-level difference with regression modelling: 2.9, 95%CI: 1.14-4.6, P<0.001).
  • KCCQ-OS consists of 4 equally-weighted domains: physical limitation (PL), symptom frequency (SF), QoL and social limitation (SL). Improvements were largest in the PL (4.8 ± 24.8 vs. 2.0 ± 22.2 points) and QoL (6.4 ± 23.9 vs. 2.7 vs. 24.1 points) domains.
  • Similar findings were seen in de novo users of ARNI (mean difference: 2.9, 95%CI: 0.3-5.5, P=0.028) and in those who switched from ACEi/ARB to ARNI therapy (2.7, 95%CI: 0.4-5.0, P=0.024).
  • 43.7% of ARNI patients vs 39.8% of the no-ARNI patients experienced at least a moderate improvement in health status, and 32.7% vs. 26.9% a large, and 20.5% vs. 12.1% a very large benefit. - Numbers needed to treat (NNT) for 1 patient to have a large benefit was 18 (95%CI: 10-111) and for a very large health status benefit was 12 (95%CI: 9-24).


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.


1. Pokharel Y, Khariton Y, Tang Y, et al. Association of serial Kansas City Cardiomyopathy Questionnaire assessments with death and hospitalization in patients with heart failure with preserved and reduced ejection fraction: a secondary analysis of 2 randomized clinical trials. JAMA Cardiol 2017;2: 1315–21.

2. Kosiborod M, Soto GE, Jones PG, et al. Identifying heart failure patients at high risk for near term

cardiovascular events with serial health status assessments. Circulation 2007;115:1975–81.

3. Soto GE, Jones P, Weintraub WS, et al. Prognostic value of health status in patients with heart failure after acute myocardial infarction. Circulation 2004;110:546–51.

4. Spertus J, Peterson E, Conard MW, et al. Monitoring clinical changes in patients with heart

failure: a comparison of methods. Am Heart J 2005;150:707–15.

5. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993–1004

6. DeVore AD, Thomas L, Albert NM, et al. Change the management of patients with heart failure: rationale and design of the CHAMP-HF registry. Am Heart J 2017;189:177–83.

Find this article online at JACC: Heart Failure

Facebook Comments

Schedule30 May 2024