AbstractBackgroundRandomized controlled trials (RCT) generalizability may be limited due to strict patient selection.ObjectiveIn 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)].MethodsOutpatients 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).ResultsOf 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.ConclusionIn 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.