PARADIGM-HF eligibility in historical German HFrEF populations: clinical characteristics and 1-year outcomes.

BACKGROUND: In the PARADIGM-HF trial, sacubitril/valsartan improved outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Because patients enrolled in randomized trials often differ from those in routine care, we assessed the proportion and characteristics of patients fulfilling PARADIGM-HF eligibility criteria in historical German HFrEF datasets and used the PARADIGM-HF enalapril arm as descriptive clinical context. METHODS AND RESULTS: We analyzed 7605 HFrEF patients enrolled between 1994 and 2013 in three German datasets (EVITA-HF, HeLuMa, INH). Full eligibility, including natriuretic peptide (NP) criteria, was assessable in 4442 patients and confirmed in 1828 (41.2%). Mean age was 63.8 ± 13.3 years, 23.1% were female, and ischemic heart disease was the predominant etiology (51.7%). Compared with non-PARADIGM patients, PARADIGM-like patients were older, had lower LVEF, higher NP concentrations, and more comorbidities. In an exploratory pooled Cox analysis, the unadjusted HR of the PARADIGM-like patients for one-year all-cause mortality was 1.17 (95% CI 0.97-1.40) and was attenuated to 1.08 (95% CI 0.90-1.30) after adjustment for age, sex, NYHA functional class III/IV, LVEF, and renal function. Descriptive contextualization against the PARADIGM-HF enalapril arm showed overlap in clinical characteristics but also differences in disease severity, biomarker concentrations, and ascertainment conditions. CONCLUSIONS: In these historical German HFrEF datasets, full PARADIGM-HF eligibility including NP criteria was confirmed in 41.2% of patients with completely assessable eligibility information, indicating that PARADIGM-HF included a high rate of patients seen in routine care. PARADIGM-like compared to non-PARADIGM-like patients exhibited a more advanced clinical profile.