News - June 23, 2020

Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real world data from the Swedish Heart Failure Registry

HFA Discoveries 2020 webinar presented by Gianluigi Savarese (Stockholm, Sweden)

In the PARADIGM-HF trial, treatment with sacubitril/valsartan reduced the risk of the primary endpoint, a composite of CV death and HF hospitalization, by 20% compared to enalapril in HF patients with reduced ejection fraction. Sacubitril/valsartan was also tested in HFpEF patients (those with EF ≥45), in the PARAGON-HF trial. Lower rates of CV death and HF hospitalization were observed with sacubitril/valsartan compared to valsartan alone, but the difference was not significant. A prespecified subgroup analysis of PARAGON-HF demonstrated potential efficacy of sacubitril/valsartan in those with EF below the median of 57%. Therefore, the benefit of sacubitril/valsartan in PARADIGM-HF could be extended to mildly reduced EF and may even challenge the definition of HFrEF to inlude HFmrEF.

To increase potential treatment effects in studies and reducing the sample size needed, criteria are applied to patients. The generalizability of findings is therefore questionable, and can lead to limiting implementation of treatments in clinical practice.

In this study, the proportion and characteristics of HF patients with reduced/mildly reduced (EF <50%) and with mildly-reduced/preserved EF (EF ≥40%) who would be eligible for sacubitril/valsartan based on PARADIGM-HF and PARAGON-HF criteria was assessed.

Data of 37,790 outpatients with known EF from the Swedish HF registry (SwedeHF) were used. Two potential scenarios were applied: a literal scenario (all trials inclusion/exclusion criteria which could be assessed in the database) and a pragmatic scenario (considering inclusion/exclusion criteria which may be more likely to influence the likelihood of receiving sacubitril/valsartan in clinical practice).

Main results

• 81% of patients had EF<50%. In those with EF <50%, 29% were eligible based on the literal scenario and 63% based on the pragmatic scenario. This was 19% based on the literal scenario in those with EF ≥40% and 52% based on the pragmatic scenario. Similar eligibility was observed for those with EF 40-49% and those with EF ≥50%.
• Inclusion criteria that had an impact on eligibility were diuretic use or use of ACEi/ARBs, NYHA class and NT-proBNP criteria. For exclusion criteria these were: history of ACS, SBP<110/100 mmHg, kidney failure (eGFR <30).
• Compared to non-eligible patients, eligible patients were older, more likely female, less likely to be referred to speciality care, more severe HF, more comorbidities, more likely to use diuretics.
• In the pragmatic scenario, higher event rates were observed for all outcomes in eligible patients compared to non-eligible patients, regardless of EF. In the literal scenario, also higher event rates were observed for all outcomes in eligible patients compared to non-eligible patients, except for lower event rates in eligible patients compared to non-eligible patients with EF<50% or EF <40%.

Conclusions

Eligibility was assessed in a cohort of real-world Swedish HF patients, of which 81% had EF<50%. Eligibility was similar in those with EF 40-49% and those with EF ≥50%, suggesting that eligibility estimates may be reproduced for EF <50% when a higher cutoff for EF is applied. In addition, this study examined characteristics and outcomes in eligible vs. non-eligible patients.

- Our reporting is based on the information provided by the HFA Discoveries webinar -