Dabigatran beats out other new anticoags, maybe

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pharma decisions - 55.24 Kb

While there were “no profound significant differences” in efficacy between apixaban and both doses of dabigatran or rivaroxaban, dabigatran 150 mg twice-daily was superior to rivaroxaban for some efficacy endpoints, whereas major bleeding was significantly lower with dabigatran 110 mg twice-daily or apixaban. So found an indirect comparison analysis published in the Aug. 21 issue of the Journal of the American College of Cardiology, in which the authors acknowledged the results should not be “over-interpreted.”

Data for warfarin compared against the new oral anticoagulants in large phase III clinical trials of stroke prevention in atrial fibrillation are now available for the oral direct thrombin inhibitor, dabigatran etexilate (Pradaxa, Boehringer Ingelheim), in two doses (150 mg twice-daily [BID], 110 mg BID), and the oral Factor Xa inhibitors, rivaroxaban (Xarelto, Janssen Pharmaceuticals, a Johnson & Johnson company/Bayer HealthCare) and apixaban (Eliquis, Bristol Myers Squibb/Pfizer).  

A “head-to-head” direct comparison of drugs is the standard method for comparing different treatments, but in the absence of such head-to-head direct comparisons, another alternative to assess the relative effect of different treatment interventions would be to perform indirect comparisons, using a common comparator, according to Gregory Y. H. Lip, MD, of the University of Birmingham Centre for Cardiovascular Sciences at City Hospital in Birmingham, England, and colleagues. However, they acknowledged that 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.”

Assessing the main efficacy and safety endpoints from the RE-LY, ROCKET-AF and ARISTOTLE trials, the researchers found that there was a significantly lower risk of stroke and systemic embolism (by 26 percent) for dabigatran (150 mg BID) compared with rivaroxaban, as well as hemorrhagic stroke and non-disabling stroke. There were no significant differences for apixaban versus dabigatran (both doses) or rivaroxaban; or rivaroxaban versus dabigatran 110 mg BID in preventing stroke and systemic embolism.

For ischemic stroke, they found no significant differences between the new oral anticoagulants.

Major bleeding was significantly lower with apixaban compared with dabigatran 150 mg BID (by 26 percent) and rivaroxaban (by 34 percent), but not significantly different from dabigatran 110 mg BID, according to Lip et al’s findings.

“Bleeding is clearly an endpoint of concern in anticoagulated atrial fibrillation patients,” the authors wrote. While there were no significant differences between apixaban and dabigatran 110 mg BID in safety endpoints, apixaban had lower major or clinically relevant bleeding (by 34 percent) 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). There were no significant differences in myocardial infarction events between dabigatran (both doses) and apixaban.

With respect to their findings, the study authors said that only a head-to-head direct comparison of the different new oral anticoagulants would fully answer the question of efficacy and safety differences between the new drugs for stroke prevention in atrial fibrillation.