Effectiveness and safety of cardiac glycosides in HFrEF: target trial emulation and transportability of DIG and DIGIT-HF effects to a contemporary real-world population

Study summary

No information provided.

Study identification

• EU PAS number:
  EUPAS1000001109
• Study ID:
  1000001109
• Official title and acronym:
  Effectiveness and safety of cardiac glycosides in HFrEF: target trial emulation and transportability of DIG and DIGIT-HF effects to a contemporary real-world population
• DARWIN EU® study:
  No
• Study countries:
  France

  Sweden
• Study description:
  Digoxin may be considered to reduce hospitalisations in patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm according to ESC guidelines, based primarily on secondary outcomes of the 1997 DIG trial, whose neutral primary outcome was all-cause mortality. The recently published DIGIT-HF trial demonstrated that the pharmacologically similar agent digitoxin significantly reduced the risk of all-cause mortality or HF hospitalisation. This has renewed interest in both cardiac glycosides, and digoxin is currently being investigated at low doses in patients with HFrEF or HF with mildly reduced ejection fraction, irrespective of heart rhythm, in the DECISION trial.; ; This study contextualises evidence on cardiac glycosides in a contemporary Swedish real-world HF population. Aim 1: to estimate the effectiveness and safety of digoxin versus standard of care without digoxin by transporting the causal effect estimated in DIG individual patient data to the SwedeHF population in sinus rhythm, combined with a target trial emulation in patients with atrial fibrillation/flutter; both analyses are merged into a single enriched treatment effect. Aim 2: to estimate the effectiveness and safety of digitoxin versus standard of care by transporting the causal effect estimated in DIGIT-HF individual patient data to a DIGIT-HF-eligible SwedeHF population.; ; Data sources comprise the SwedeHF registry (index registrations 2017–2024), linked to the LISA database, the National Patient Register, the National Prescribed Drug Register, and the Cause of Death Register. The primary outcome is the risk difference of all-cause mortality or first HF hospitalisation at 36 months, estimated using AIPCW-based one-step estimators with cross-fitting. Findings are intended to inform the decision on whether, and which, cardiac glycoside to use in Sweden and comparable countries.
• Study status:
  Ongoing

Research institutions and networks

Institutions

Karolinska Institutet

Sweden

Centre for Research in Epidemiology and Statistics (Paris, France)

Networks

More-EUROPA (Horizon Europe)

Study timelines

Date when funding contract was signed

Planned:05/02/2026

Actual:05/02/2026

Study start date

Planned:08/04/2026

Actual:08/04/2026

Data analysis start date

Planned:07/09/2026

Date of final study report

Planned:01/03/2027

Sources of funding

EU institutional research programme

Other public funding (e.g. hospital or university)

More details on funding

This work is supported by the Horizon Europe programme (project number 101095479 - More-EUROPA). Dr Beer is supported by a grant of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation; grant number 535014557).

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable