Archief Roodbont

Several alternatives to warfarin for prevention of venous thromboembolism and stroke are already approved for clinical use, and several more are in development. The principal advantage of these agents is their ease of use. Yet they also have known disadvantages — such as the lack of a rapid reversal agent and cost — and, possibly, unknown toxicities. By contrast, warfarin has been in use for millions of patient-years, and its effects (both beneficial and adverse) are very familiar.

Dabigatran was FDA-approved for treatment of atrial fibrillation after the landmark RE-LY study (JW Cardiol Sep 1 2009). A secondary finding from RE-LY showed a significant increase in myocardial infarction with dabigatran. To find out more, investigators conducted a meta-analysis of seven dabigatran studies. Control agents in the studies included warfarin, enoxaparin, and placebo.

The rate of acute coronary syndromes (including infarction) was significantly higher in the 20,000 dabigatran patients than in the 10,514 control patients (1.19% vs. 0.79%). These results were largely driven by RE-LY, which contributed 59% of the cohort and 74% of the events. Unlike the RE-LY trial, in which a decrease in overall mortality with dabigatran did not quite achieve statistical significance (P=0.051), the meta-analysis demonstrated a significant reduction in mortality with dabigatran (5.02% vs. 4.83%; P=0.04).

Comment: The confirmation of one adverse endpoint in the RE-LY study does not diminish the fact that dabigatran reduces the rates of venous thromboembolism and stroke. However, this meta-analysis does underline the need for continuing postapproval study of any new drug. I suspect that as data accumulate from registry and other observational studies, warfarin will fare poorly in overall safety comparisons with dabigatran and other new competitors.

— Mark S. Link, MD

Published in Journal Watch Cardiology February 15, 2012