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

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection.

OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective) / PARAGON-HF [sacubitril/valsartan effective in mildly-reduced ejection fraction (EF)].

METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analyzed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF≤57% (i.e. median). We defined reduced EF / PARADIGM-HF as EF<40%, mildly-reduced EF / PARAGON-HF ≤median as EF 40-49%, and normal EF / PARAGON-HF >median as EF ≥50%. We assessed 2 scenarios: 1) criteria likely to influence treatment decisions (pragmatic scenario); 2) all criteria (literal scenario).

RESULTS: Of 37,790 outpatients, 57% had EF<40%, 24% EF 40-49%, and 19% EF≥50%. In the pragmatic scenario, 63% were eligible in EF<50% (67% for EF<40% and 52% for 40-49%) and 52% in EF≥40% (52% for EF≥50%). For the literal scenario, 32% were eligible in EF<50% (38% of EF<40%, 20% of EF 40-49%) and 22% in EF≥40% (25% for EF≥50%). Eligible vs. non-eligible patients had more severe HF, more comorbidities and overall worse outcomes.

CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF <50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF<50% may be reproduced whether or not a higher cut-off for EF is considered.