An indirect comparison analysis of three new oral anticoagulants (OACs) – dabigatran etexilate (two doses), rivaroxaban, and apixaban  – found no profound significant differences in efficacy between the new agents, but benefits of each over warfarin.

"Only a head-to-head direct comparison of the different new OACs would fully answer the question of efficacy/safety differences between the new drugs for stroke prevention in [atrial
fibrillation]," the study authors said.

"Unfortunately, no trials have been conducted (yet) that directly compare one new agent versus another," write Christopher Cannon, MD, FACC, and Payal Kholi in a JACC editorial comment. "The pooled analysis is straightforward and shows statistically sound analysis of the data, [which] strongly supports the use of the newer agents over warfarin, as a class." However, they caution that there is "danger ahead" with indirect comparisons. They note that the differences on some endpoints are not robust enough to be relied upon for the clinical care of patients. Providers should "turn to direct evidence from trials and the indications put forth by the FDA to select the appropriate agent, at the dose tested, for use in the patient population studied within the trial," they write. 

The study authors also cautioned against over-interpreting the study results. "Any inter-trial comparison is always fraught with major difficulties, and an indirect comparison analysis has many limitations, especially with the inter-trial population differences and thus, should not be over-interpreted," they said.