Dabigatran versus Warfarin in Patients with Atrial Fibrillation
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Abstract
To the Editor: Although Connolly et al. (Sept.
17 issue)1 have demonstrated a modest advantage
for dabigatran over warfarin in atrial fibrillation,
we think the benefit could be even greater.
Warfarin has many adverse properties. Vitamin
K content varies widely in foods. Warfarin
inhibits the synthesis of sequential enzymes in
the coagulation cascade, which imparts a drastically
steep dose\u96response relationship. The binding
of warfarin to plasma proteins and its metabolism
by cytochrome P-450 enzymes facilitate
drug interactions. These properties result in variability
in anticoagulant control, which is associated
with bleeding, thrombosis, and increased
risk of death.2-5
Dabigatran lacks these undesirable properties.
But the adoption of \u93one size fits all\u94 dosing has
probably undermined the performance of dabigatran
in the trial for the Randomized Evaluation
of Long-Term Anticoagulation Therapy (RE-LY).
Dabigatran appeared to be more efficacious in
patients who weighed less and in patients with
impaired renal function (in whom the drug accumulates),
pointing to significant interpatient
variability in response. Individualized dosing,
based on weight and estimated creatinine clearance,
might improve the drug\u92s risk\u96benefit ratio.
Dosing could be further refined with the use of
a single measurement of the drug level drawn at
steady state, if necessary. Such an approach
should be studied.
Donald Stuart Houston, M.D., Ph.D.
Ryan Zarychanski, M.D