Cardiovascular

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

TL;DR

Full PARADIGM-HF eligibility including natriuretic peptide criteria was confirmed in 41.2% of historical German HFrEF patients with completely assessable eligibility information, indicating that PARADIGM-HF included a high rate of patients seen in routine care.

Key Findings

Among historical German HFrEF patients with fully assessable eligibility criteria, 41.2% met full PARADIGM-HF eligibility including natriuretic peptide criteria.

  • Total study population was 7605 HFrEF patients enrolled between 1994 and 2013 in three German datasets (EVITA-HF, HeLuMa, INH).
  • Full eligibility including natriuretic peptide criteria was assessable in 4442 patients.
  • Of the 4442 assessable patients, 1828 (41.2%) confirmed full PARADIGM-HF eligibility.
  • The authors concluded this indicates 'PARADIGM-HF included a high rate of patients seen in routine care.'

PARADIGM-like patients in the historical German datasets were older, had lower LVEF, higher natriuretic peptide concentrations, and more comorbidities compared to non-PARADIGM-like patients.

  • Mean age of PARADIGM-like patients was 63.8 ± 13.3 years.
  • 23.1% of PARADIGM-like patients were female.
  • Ischemic heart disease was the predominant etiology at 51.7%.
  • PARADIGM-like patients exhibited 'a more advanced clinical profile' compared to non-PARADIGM-like patients.

PARADIGM-like patients had a numerically higher unadjusted one-year all-cause mortality risk compared to non-PARADIGM-like patients, which was attenuated after multivariable adjustment.

  • In an exploratory pooled Cox analysis, the unadjusted hazard ratio for one-year all-cause mortality in PARADIGM-like patients was 1.17 (95% CI 0.97–1.40).
  • After adjustment for age, sex, NYHA functional class III/IV, LVEF, and renal function, the HR was attenuated to 1.08 (95% CI 0.90–1.30).
  • Both the unadjusted and adjusted confidence intervals crossed 1.0, indicating no statistically significant difference.
  • The analysis was described as 'exploratory.'

Descriptive comparison of historical German PARADIGM-like patients against the PARADIGM-HF enalapril arm showed overlap in clinical characteristics but also differences in disease severity, biomarker concentrations, and ascertainment conditions.

  • The PARADIGM-HF enalapril arm was used as 'descriptive clinical context,' not for formal statistical comparison.
  • Differences were noted in disease severity and biomarker concentrations between the historical German cohorts and the PARADIGM-HF enalapril arm.
  • Ascertainment conditions also differed between the historical datasets and the trial setting.
  • The comparison was explicitly framed as 'descriptive contextualization' rather than an inferential analysis.

Natriuretic peptide eligibility criteria represented a key limiting factor in determining full PARADIGM-HF eligibility, as NP data were not assessable in all patients.

  • Of the total 7605 HFrEF patients, full eligibility including NP criteria was assessable in only 4442 patients.
  • This means NP data or other eligibility components were missing or unassessable in 3163 patients (approximately 41.6% of the total cohort).
  • The three datasets (EVITA-HF, HeLuMa, INH) were enrolled between 1994 and 2013, predating routine NP measurement in some clinical settings.

What This Means

This research examined how many patients with heart failure and reduced pumping function (HFrEF) treated in routine German clinical care would have been eligible to participate in the landmark PARADIGM-HF clinical trial, which demonstrated that the drug sacubitril/valsartan improves outcomes compared to enalapril. The researchers analyzed records from 7,605 heart failure patients enrolled in three German registries or studies between 1994 and 2013. Among the roughly 4,400 patients for whom all necessary eligibility information—including blood biomarker (natriuretic peptide) levels—could be assessed, about 41% met all the PARADIGM-HF entry criteria. This suggests that the PARADIGM-HF trial enrolled a patient population that substantially overlaps with patients seen in everyday clinical practice. Patients who met the PARADIGM-HF eligibility criteria tended to have more severe disease than those who did not qualify: they were older, had weaker heart function (lower ejection fraction), higher biomarker levels indicating heart stress, and more additional health conditions. Despite this more advanced clinical profile, their one-year risk of death was only modestly and non-significantly higher than non-eligible patients, particularly after accounting for differences in age, sex, heart function, and kidney function. When the German registry patients who met eligibility criteria were compared descriptively to patients in the enalapril (control) arm of PARADIGM-HF, there was considerable overlap in clinical features, though some differences in disease severity and measurement conditions existed. This research suggests that the results of the PARADIGM-HF trial may be broadly applicable to HFrEF patients seen in routine clinical practice in Germany and potentially other similar healthcare settings. The finding that about 4 in 10 real-world HFrEF patients meet trial eligibility criteria supports the generalizability of the trial, while also highlighting that eligibility assessment requires complete biomarker data, which may not always be available in everyday care. The more advanced disease profile of eligible patients underscores the importance of timely identification and treatment of high-risk heart failure patients.

Have a question about this study?

Citation

Hobbach A, Hochadel M, Angermann C, Störk S, Senges J, Zeymer U. (2026). PARADIGM-HF eligibility in historical German HFrEF populations: clinical characteristics and 1-year outcomes.. International journal of cardiology. https://doi.org/10.1016/j.ijcard.2026.134749