Eligibility For Sacubitril/Valsartan In Heart Failure Across The Ejection Fraction Spectrum: Real-World Data From The Swedish Heart Failure Registry (Vol 289, Pg 369, 2021)

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 analysed. 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: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) 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. noneligible 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.