Interactions Between Left Ventricular Ejection Fraction, Sex and Effect of Neurohumoral Modulators in Heart Failure
Key result
Treatment with neurohumoral modulators benefited women at higher LVEF than men, with women having mean LVEF 6.3%, 9.4%, and 10.3% higher than men across the respective trial pools.
Why the study?
To further investigate the relationship between sex, LVEF, and treatment response to neurohumoral modulators across the full range of HF phenotypes.
Does treatment with neurohumoral modulators (ARB, MRA, ARNI) have a differential effect based on sex and LVEF in patients with heart failure?
Comparison
Candesartan, MRAs, or sacubitril/valsartan vs trial control groups
Design
Pooled individual patient-level post hoc analysis of clinical trials
Authors
Discussion
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Member takes
Implication
May support higher LVEF thresholds for neurohumoral therapy benefit in women with HF; extends meta-analytic evidence on sex-specific responses.
Study Design
Type
Meta-Analysis (n=26,961)
Multicenter
Yes
Structured PICO
Does treatment with neurohumoral modulators (ARB, MRA, ARNI) have a differential effect based on sex and LVEF in patients with heart failure?
P
Population
26,961 patients with heart failure across the full range of LVEF, pooled from multiple clinical trials to assess sex and LVEF interactions with neurohumoral modulators.
I
Intervention
Neurohumoral modulators (candesartan, mineralocorticoid receptor antagonists, or sacubitril/valsartan)
C
Comparator
Control groups from the respective trials (placebo or active comparator)
O
Outcome
Composite of first occurrence of heart failure hospitalization or cardiovascular deathcomposite
Women with heart failure may derive clinical benefit from neurohumoral modulators at higher left ventricular ejection fractions than men, suggesting sex-specific LVEF thresholds for treatment efficacy.
Limitations
- Post hoc analyses, only hypothesis generating
- Interpretation of PARAGON-HF is more complex as it had an active comparator compared with a placebo control in the other trials
- Post hoc analyses
- Hypothesis generating
- PARAGON-HF had an active comparator compared with a placebo control in the other trials
Cite This Study
Dewan et al. (2020) conducted a meta-analysis in Heart failure (n=26,961). Neurohumoral modulators (ARB, MRA, or ARNI) vs. Placebo or active comparator was evaluated on First occurrence of HF hospitalization or cardiovascular death. Treatment with neurohumoral modulators benefited women at higher LVEF than men, with women having mean LVEF 6.3%, 9.4%, and 10.3% higher than men across the respective trial pools.