- In patients with heart failure (HF), the therapeutic effects of sacubitril/valsartan vs renin-angiotensin-system (RAS) inhibitor alone varied by left ventricular ejection fraction (LVEF), with greatest therapeutic benefits in those with ejection fraction (EF) below the normal range.
- These therapeutic benefits appeared to extend to a higher LVEF range in women than men.
Why this matters
- Findings suggest that patients with EF lower than normal, which includes those with so-called heart failure with mid-range EF or borderline EF would likely benefit from sacubitril/valsartan compared with RAS inhibition.
- Study evaluated combined data from PARADIGM-HF (n=8399) and PARAGON-HF (n=4796) trials.
- All patients with HF were divided into LVEF categories:
- ≤40%: n=8397;
- >40 to 50%: n=730; and
- >50%: n=4067.
- Time to first CV death and hospitalisation for HF (HHF), its components, all-cause mortality, total HHF and CV death and total HHF were evaluated.
- Funding: Novartis.
- Sacubitril/valsartan was superior to RAS inhibitors in terms of:
- time to first CV death or HHF (HR, 0.84; 95% CI, 0.78-0.90);
- CV death (HR, 0.84; 95% CI, 0.76-0.92);
- HHF (HR, 0.84; 95% CI, 0.77-0.91);
- all-cause mortality (HR, 0.88; 95% CI, 0.81-0.96);
- total HHF and CV death (HR, 0.82; 95% CI, 0.75-0.89); and
- and total HHF (HR, 0.81; 95% CI, 0.73-0.90).
- Interaction analyses suggested that LVEF was a significant effect modifier of the treatment effect of sacubitril/valsartan for first CV death and HHF (Pinteraction=.02) and therapeutic benefits were greater in patients with EF below the normal range.
- Effect modification by LVEF on the efficacy of sacubitril/valsartan was similar in both men and women, but the treatment benefits persisted to higher EF in women vs men (Pinteraction=.032).
- Semi-quantitative estimation of LVEF by site investigators.