Reverse Cardiac Remodeling Following Initiation of Sacubitril/Valsartan in Patients With Heart Failure With and Without Diabetes

Objective: This study sought to determine whether patients with heart failure and reduced ejection fraction (HFrEF) with type 2 diabetes mellitus (T2DM) have similar reverse cardiac remodeling with sacubitril/valsartan as patients without T2DM.

Background: Sacubitril/valsartan promotes reverse cardiac remodeling and improves outcomes in patients with HFrEF. Patients with HFrEF with T2DM have worse prognosis than those without T2DM.

Methods: In this post hoc analysis of PROVE-HF (Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure), we examined changes in N-terminal pro-b-type natriuretic peptide (NT-proBNP), measures of cardiac remodeling, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) scores from baseline to 12 months following initiation of sacubitril/valsartan between patients with HFrEF with and without T2DM. Using latent growth curve modeling, we evaluated the longitudinal association between changes in NT-proBNP, left ventricular ejection fraction, and KCCQ-OS.

Results: Among 794 patients enrolled, 361 (45.5%) had T2DM. NT-proBNP concentrations were modestly higher at baseline among patients with T2DM but were reduced after initiation of sacubitril/valsartan. Cross-sectional improvement was observed in left ventricular ejection fraction (T2DM: 28.3% at baseline and 37% at 12 months vs. non-T2DM: 28.1% at baseline and 38.3% at 12 months) and KCCQ-OS (T2DM: 71 at baseline and 83 at 12 months vs. non-T2DM: 76 at baseline and 88 at 12 months). Similar changes were also observed for other echocardiographic measures. In longitudinal analyses, the average NT-proBNP change was similar in patients with T2DM (-5.6% vs. -7.1% per 90-day interval; p = 0.64), whereas improvements in KCCQ-OS scores were slightly smaller (2.1 vs. 3.46 per 90-day interval; p = 0.07).

Conclusions: Sacubitril/valsartan favorably affects natriuretic peptide levels, reverse cardiac remodeling, and health status in patients with HFrEF with and without T2DM. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).