Summary
In the RE-LY trial dabigatran 150 mg twice daily (D150) showed significantly fewer
strokes, and 110 mg (D110) significantly fewer major bleeding events (MBE) compared
to well-controlled warfarin in patients with atrial fibrillation (AF). The European
(EU) label currently recommends the use of D150 in AF patients who are aged < 80 years
without an increased risk for bleeding (e.g. HAS-BLED score <3) and not on concomitant
verapamil. In other patients, D110 is recommended. In this post-hoc analysis of the
RE-LY dataset, we simulated how dabigatran (n=6,004) would compare to well-controlled
warfarin (n=6,022) used according to the EU label. “EU label simulated dabigatran
treatment” was associated with significant reductions in stroke and systemic embolism
(hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60–0.91), haemorrhagic stroke
(HR 0.22; 95%CI 0.11–0.44), death (HR 0.86; 95%CI 0.75–0.98), and vascular death (HR
0.80; 95%CI 0.68–0.95) compared to warfarin. Dabigatran was also associated with less
major bleeding (HR 0.85; 95%CI 0.73–0.98), life-threatening bleeding (HR 0.72; 95%CI
0.58–0.91), intracranial haemorrhage (HR 0.28; 95%CI 0.17–0.45), and “any bleeds”
(HR 0.86; 95%CI 0.81–0.92), but not gastrointestinal major bleeding (HR 1.23; 95%CI
0.96–1.59). The net clinical benefit was significantly better for dabigatran compared
to warfarin. In conclusion, this post-hoc simulation of dabigatran usage based on
RE-LY trial dataset indicates that “EU label simulated dabigatran treatment” may be
associated with superior efficacy and safety compared to warfarin, and are in support
of the EU label and the 2012 European Society of Cardiology AF guideline recommendations.
Thus, adherence to European label/guideline use results in a clinically relevant benefit
for dabigatran over warfarin, for both efficacy and safety.
Note: The editorial process for this paper was fully handled by Prof Christian Weber,
Editor in Chief.
Keywords
Atrial fibrillation - dabigatran - net clinical benefit - warfarin
