Sex‐based differences in biomarkers, health status, and reverse cardiac remodelling in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan

Abstract

Aims We sought to determine sex‐based differences in biomarkers, self‐reported health status, and magnitude of longitudinal changes in measures of reverse cardiac remodelling among patients with heart failure with reduced ejection fraction (HFrEF, left ventricular ejection fraction ≤40%) treated with sacubitril/valsartan (S/V). Methods and results This was a subgroup analysis of patients initiated on S/V in the Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE‐HF) study. There were 226 (28.5%) women in the study. Though women had lower baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP), they had more rapid early reduction in the biomarker after initiation of S/V. Compared to men, women had lower average baseline Kansas City Cardiomyopathy Questionnaire (KCCQ)‐23 Total Symptom score (67.6 vs. 71.9; P = 0.003) but showed greater linear improvement (7.4 vs. 5.5 points; P < 0.001) and faster pace of KCCQ change (P < 0.001) over the course of the trial. Women and men demonstrated similar degrees of reverse left ventricular remodelling following S/V initiation; however, women did so earlier than men with more consistent changes. These results remained unchanged with adjustment for relevant covariates. Reduction in NT‐proBNP was associated with reverse cardiac remodelling in both women and men. Treatment with S/V was well tolerated in all. Conclusions In women with HFrEF, treatment with S/V was associated with significant NT‐proBNP reduction, health status improvement and reverse cardiac remodelling.

Sacubitril/Valsartan in the Treatment of Right Ventricular Dysfunction in Patients With Heart Failure With Reduced Ejection Fraction: A Real-world Study

“…Notably, the value of sacubitril/valsartan treatment for reversing LV remodeling in patients with HFrEF has been confirmed in recent years. 3,22,23 In our study, we found that the degree of TAPSE improvement was closely associated with improvements in LVEF and LVESV after adjusting for age. This association between RV function and LV remodeling was revealed to be an independent one after adjusting for echocardiographic variables.…”

ARNI versus ACEI/ARB in Reducing Cardiovascular Outcomes after Myocardial Infarction

“…This indicates that ARNI might exert long‐term cardiovascular benefits on female patients, and the exact mechanism remains to be explored. 23 …”

“…This correlates to the findings from the PARAGON study 22 that ARNI treatment reduced the primary endpoint (total hospitalization for HF and risk of cardiovascular death) by 27% among female patients with HF with preserved ejection fraction. This indicates that ARNI might exert long‐term cardiovascular benefits on female patients, and the exact mechanism remains to be explored 23 …”

Heart Failure with Reduced Ejection Fraction—Does Sex Matter?

“…However, women have been observed to be less likely to receive appropriate prescription, with some studies showing female gender to be independently associated with lower odds of ARNI prescription [34,35]. This data is even more striking in the context subgroup analysis from the PROVE-HF study showing that, when compared to men, women had a more rapid and early reduction in serum N-terminal pro-BNP after ARNI initiation [36]. Furthermore, whilst women and men had similar degrees of reverse left ventricular remodelling after ARNI use, women displayed earlier and more consistent remodelling.…”