Indirect Comparison Finds No Significant Differences Between New OACs

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.

The analysis, published in the Journal of the American College of Cardiology (JACC), found that overall the new OACs resulted in a lower risk of stroke or systemic embolism, hemorrhagic stroke, and all-cause mortality compared with warfarin. Major and intracranial bleeding was also lower. However, results of the analysis did find a lower risk of stroke and systemic embolism, hemorrhagic stroke and nondisabling stroke for dabigatran (150 mg BID) compared with rivaroxaban. Major bleeding was significantly lower with apixaban compared with dabigatran (150 mg BID) and rivaroxaban, but not significantly different from dabigatran (110 mg BID). Apixaban also had lower major or clinically relevant bleeding compared with rivaroxaban. When compared with rivaroxaban, dabigatran (110 mg BID) was associated with less major bleeding (by 23 percent) and intracranial bleeding (by 54 percent).

"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.

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