Meta-analysis
Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF
- Individual patient-level network meta-analysis of randomised trials
- COMBINE AF database (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48)
- multivariable Cox model with treatment-by-CrCl interaction and random effects
Authors' conclusion
Standard-dose DOACs are safer and more effective than warfarin down to a CrCl of at least 25 mL/min. Lower-dose DOACs do not significantly lower the incidence of bleeding or ICH compared with standard-dose DOACs but are associated with a higher incidence of S/SE and death.
Study context
- Population
- Patients with AF in 4 DOAC trials, across kidney function (continuous creatinine clearance (CrCl))
- Participants
- 71,683 patients · 4 RCTs
- Comparison
- Standard-dose DOAC vs lower-dose DOAC vs warfarin across continuous CrCl
Pooled result
As reported in the abstract
S/SE, major bleeding, ICH and death by CrCl · median follow-up 23.1 months
- Intracranial hemorrhage (ICH): significantly lower hazard at CrCl <122 mL/min
- decrease in HR per 10-mL/min decrease in CrCl 6.2%; P for interaction = 0.08
- S/SE: significantly lower hazard with CrCl <87 mL/min
- decrease in HR per 10-mL/min decrease in CrCl 4.8%; P for interaction = 0.01
- death: significantly lower hazard with CrCl <77 mL/min
- decrease in HR per 10-mL/min decrease in CrCl 2.1%; P for interaction = 0.08
Further pooled results
Lower-dose vs standard-dose DOAC, reduced kidney function
- No significant difference in bleeding or ICH; higher incidence of death and S/SE with lower-dose DOAC
Original publication
Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF. Circulation. Published 12 April 2023. doi:10.1161/circulationaha.122.062752
Summarised from the published abstract; every number is checked against it