Arrhythmias & electrophysiology
Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF
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
- Outcome
- S/SE, major bleeding, ICH and death by CrCl
- Follow-up
- Median 23.1 months
Methodological detailsCOMBINE AF database (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48), multivariable Cox model with treatment-by-CrCl interaction and random effects
- COMBINE AF database (RE-LY, ROCKET AF, ARISTOTLE, ENGAGE AF-TIMI 48)
- Multivariable Cox model with treatment-by-CrCl interaction and random effects
Pooled result
As reported in the abstract
Decrease in HR per 10-mL/min decrease in CrCl
6.2%
P for interaction = 0.08
Intracranial hemorrhage (ICH): significantly lower hazard at CrCl <122 mL/min
Decrease in HR per 10-mL/min decrease in CrCl
4.8%
P for interaction = 0.01
S/SE: significantly lower hazard with CrCl <87 mL/min
Decrease in HR per 10-mL/min decrease in CrCl
2.1%
P for interaction = 0.08
death: significantly lower hazard with CrCl <77 mL/min
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
Summarised from the published abstract; every number is checked against it