Standard-dose unfractionated heparin versus low-dose unfractionated heparin and low-molecular-weight heparin in extracorporeal life support (RATE): an open-label, randomised, non-inferiority trial.

Summary

In this multicenter randomized noninferiority trial in ECMO patients, both low-dose UFH and therapeutic LMWH were noninferior to standard-dose UFH for a composite of severe bleeding, severe thromboembolism, or 6-month mortality. Severe bleeding occurred less often with lower-intensity strategies without an excess of thromboembolic events, supporting reconsideration of anticoagulation targets in ECMO.

Key Findings

• Composite primary outcome occurred in 87/107 (81%) standard-dose UFH, 78/108 (72%) low-dose UFH (risk difference -9.1 percentage points; 95% CI -20.3 to 2.1), and 79/105 (75%) LMWH (-6.1; 95% CI -17.2 to 5.0), meeting noninferiority.
• Severe bleeding was numerically lower with low-dose UFH (58%) and LMWH (59%) versus standard-dose UFH (65%), without excess severe thromboembolic events (10% and 9% vs 11%).
• Six-month mortality was 50% (standard-dose UFH), 42% (low-dose UFH), and 44% (LMWH).

Clinical Implications

Lower-intensity anticoagulation (low-dose UFH or therapeutic LMWH) can be considered as alternatives to standard-dose UFH in ECMO, potentially reducing severe bleeding without increasing thromboembolism; centers should revisit anticoagulation protocols.

Limitations

• Open-label design with potential for performance bias
• Composite endpoint may obscure differences in individual components; secondary outcomes did not reach statistical significance

Future Directions

Head-to-head blinded trials or pragmatic registries could refine patient selection, evaluate bleeding phenotypes, and assess cost-effectiveness and outpatient transitions between UFH and LMWH.