PROVE HF: Impact of Sacubitril/Valsartan Initiation on Health Status in Patients with HFrEF

1 Feb, 21

Introduction

Patients with heart failure (HF) have a poor quality of life. Treatment of HF with reduced ejection fraction (HFrEF) may improve patient-reported health outcomes. The Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 is one of the most commonly used patient-reported instrument that represents health-related attributes of HF. Increases in KCCQ-23 summary scores indicate improving results of other important objective measures in HF. Studies have demonstrated that sacubitril/valsartan treatment improves clinical outcomes and also modestly improves KCCQ-23 in patients with HFrEF. Nevertheless, the existing data on the impact of sacubitril/valsartan on KCCQ scores was influenced by a run-in-period. Data on impact of sacubitril/valsartan on KCCQ scores following initiation of treatment may provide valuable insights.

Aim

To determine timing and magnitude of change in KCCQ-23 scores following initiation of sacubitril/valsartan
To determine the interaction with change in amino terminal pro–B-type natriuretic peptide (NT-proBNP) concentrations

Patient Profile

Patients with HFrEF with left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association (NYHA) class II to IV within past 6 months (age ≤18 years; n=678 patients of the PROVE-HF population)

Methods

Study Design

A pre-specified secondary analysis of PROVE-HF trial
PROVE-HF was a phase 4, open-label, single-group study conducted across 78 sites in the United States

Treatment Strategy

Following the discontinuation of angiotensin-converting enzyme (ACE) inhibitor/ angiotensin receptor blocker (ARB), patients received sacubitril/valsartan twice daily (dose was increased every 2 to 4 weeks to achieve the target dose of 97/103 mg)

Outcomes

To characterize the change in KCCQ-23 scores following initiation of sacubitril/valsartan
To correlate the changes in KCCQ-23 scores with parallel changes in NT-proBNP or measures of reverse cardiac remodelling (in this case as a function of change in LVEF).

KCCQ-23 Assessment

The KCCQ-23 scores were assessed before discontinuation of ACE inhibitor/ ARB and initiation of sacubitril/valsartan and at every follow-up visit thereafter
Patient-level data (on KCCQ-23 score) from the randomized EVALUATE-HF study were used as historic controls

Results

Mean age of the study population was 64.7 years, 71.5% were male. At baseline, KCCQ-23 overall score (OS) was 65.6 with 32.9% (n=262) patients having an KCCQ-23 OS of ≥75, indicating excellent health.
The KCCQ-23 OS improved by a least-square mean average of 6 points (p < 0.001) in 1 month and by a least-square mean average of 9.1 points (p < 0.001) at month 2. This average increase at month 2 was maintained at each subsequent time point till the end of the study.
Notably, amongst the patients with baselines KCCQ-23 OS of <75 points at baseline, 34.4% (233/678) had an increase in KCCQ-23 OS ≥75 points at some time point during the study. Majority of the study population (236/678; 60.8%) had an increased in KCCQ-23 OS by ≥10 points and 176 (26%) had an increase in KCCQ-23 OS by ≥20 points.
Longitudinal changes in KCCQ-23 OS scores suggested an improvement in the KCCQ-23 OS scores at an average rate of 2.30 points per 90-day interval.
Following the initiation of sacubitril/valsartan, there was a rapid fall in NT-proBNP levels (-6.55% per 90-day interval).
The average baseline LVEF was 29.03%, during the study period, the LVEF improved at a rate of 2.38% per 90-day interval.
Rate of change in KCCQ-23 OS was strongly associated with change in circulating NT-proBNP concentrations (r² = -0.544; p < 0.001). Thus, smaller improvements in KCCQ-23 OS translated in less rapid reductions in NT-proBNP levels.
As per the analysis of control group of patients in EVALUATE-HF, the linear rate of increase in KCCQ-12 OS/14-day interval was higher in sacubitril/valsartan arm vs. enalapril arm (1.19 points; p=<0.001 vs. 0.37 points; p=0.06). These findings were almost identical to the findings of this study (1.08 points; p < 0.001).

Conclusions

Amongst patients with HFrEF, treatment with sacubitril/valsartan was associated with rapid and significant improvement in KCCQ-23 scores, that was sustained over a period of 12 months.
The improvement in KCCQ-23 score related significantly with change in NT-proBNP levels

J Am Coll Cardiol HF 2021;9:42–51.