What study evaluated restricted vs liberal transfusion in upper Gastrointestinal (GI) bleeding?

Villanueva Study Evaluated Restricted vs Liberal Transfusion in Upper GI Bleeding

The 2013 Villanueva et al. study published in The New England Journal of Medicine is the landmark trial that evaluated restricted versus liberal transfusion strategies in upper gastrointestinal bleeding. 1

Key Features of the Villanueva Study

• Single-center prospective study of 921 patients with severe acute upper gastrointestinal bleeding randomized to either restrictive (Hb <7 g/dL) or liberal (Hb <9 g/dL) transfusion strategies 1, 2
• Patients were stratified according to the presence or absence of liver cirrhosis 1
• The restrictive strategy demonstrated significantly improved outcomes compared to the liberal strategy, including:
  • Higher 6-week survival probability (95% vs. 91%; hazard ratio 0.55) 1
  • Lower rebleeding rates (10% vs. 16%) 1
  • Fewer adverse events (40% vs. 48%) 1
  • Significantly fewer transfusions (51% of restrictive group patients received no transfusions vs. only 14% in the liberal group) 1

Impact and Validation of the Villanueva Study

• This study provided Level I evidence supporting restrictive transfusion practices in upper GI bleeding 2
• The findings have been corroborated by subsequent meta-analyses showing that restrictive transfusion strategies in GI bleeding are associated with:
  • Reduced mortality (RR 0.65,95% CI 0.44-0.97) 3
  • Lower rebleeding rates (RR 0.58,95% CI 0.40-0.84) 3
  • Shorter hospital stays 4
  • Fewer blood units transfused 4

Additional Supporting Studies

• The TRIGGER trial (2015) was a pragmatic, open-label, cluster randomized feasibility trial across six UK hospitals that further evaluated restrictive (Hb <80 g/L) vs. liberal (Hb <100 g/L) transfusion strategies 5
• A 2021 single-center RCT by Saudi researchers confirmed the non-inferiority of restrictive (Hb <7 g/dL) compared to liberal (Hb <8 g/dL) transfusion strategies in UGIB 6

Clinical Practice Implications

• Current guidelines from the American College of Chest Physicians (2024) recommend a restrictive RBC transfusion strategy for patients with acute gastrointestinal bleeding 2
• The European Society of Intensive Care Medicine (2021) similarly suggests a restrictive (7 g/dL) transfusion threshold over a liberal (9 g/dL) threshold for non-massive gastrointestinal bleeding 2
• The restrictive strategy has demonstrated benefits in patients both with and without portal hypertension-related GI bleeding 2

Important Clinical Considerations

• The restrictive transfusion approach has been shown to reduce:
  • 30-day mortality (RR 0.68,95% CI 0.48-0.97) 2
  • Acute transfusion reactions (RR 0.35,95% CI 0.20-0.61) 2
  • Volume overload (RR 0.13,95% CI 0.03-0.54) 2
• A key exception to consider is patients with acute coronary syndrome, where more liberal transfusion strategies may be beneficial 2
• The portal pressure gradient increased significantly in patients assigned to the liberal strategy but not in those assigned to the restrictive strategy, which may explain the higher rebleeding rates with liberal transfusion 1