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
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 . 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  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.
- 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.