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 a multicenter randomized non-inferiority trial of 320 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. Lower-intensity strategies showed a trend toward less severe bleeding without an increase in thromboembolism, supporting reconsideration of anticoagulation targets in ECMO.

Key Findings

• Low-dose UFH and therapeutic LMWH were noninferior to standard-dose UFH for the composite of severe bleeding, severe thromboembolic complications, or 6‑month mortality.
• Severe bleeding was numerically lower with low-dose UFH (58%) and LMWH (59%) than with standard-dose UFH (65%), without excess severe thromboembolism.
• All-cause mortality at 6 months was 50% (standard UFH), 42% (low-dose UFH), and 44% (LMWH).
• Noninferiority margin was an absolute risk difference of 7.5 percentage points; both interventions met this criterion.

Clinical Implications

Centers may safely consider lower-intensity anticoagulation (low-dose UFH or LMWH) during ECMO, balancing bleeding and thrombosis risks while monitoring local protocols and patient-specific indications.

Limitations

• Open-label design could introduce performance bias
• Bleeding and thromboembolism differences were not statistically significant despite favorable trends

Future Directions

Head-to-head pragmatic trials comparing LMWH vs UFH with standardized bleeding definitions, and subgroup analyses (VV vs VA ECMO, surgical vs medical) to refine anticoagulation targets.