Post-hoc Analysis Provides Rationale for Lower Dosage of Pradaxa

A new post-hoc analysis of the RE-LY trial—the pivotal trial of Boehringer Ingelheim's Pradaxa (dabigatran)—suggests that the lower, 110-mg tablet should be available for elderly patients. In a recent online report at the Circulation website, reported yesterday by heartwire, the risk of extracranial bleeding was found to be significantly higher with the 150-mg bid dosage in patients older than 74 years of age (table below adapted from heartwire).

Endpoint	Warfarin, %	Pradaxa 110 mg bid, %	Pradaxa 150 mg bid, %	P
Major bleeding
All ages	3.57	2.87	3.31	.002*
Age <75	3.04	1.89	2.12	—
Age ≥75	4.37	4.43	5.10	<.001*
Extracranial bleeding
Age <75	2.44	1.76	1.91	—
Age ≥75	3.44	4.10	4.68	.001*
Intracranial bleeding
Age <75	0.61	0.14	0.26	—
Age ≥75	1.00	0.37	0.41	.28*

* P for interaction.

Consequently the lead author of the analysis, Eikelboom, concludes to heartwire that these new data "support the need for both doses of dabigatran to be made available in the US. The 150-mg dose will be the dose of choice in the under-75s but in older patients clinicians will want to consider the 110-mg dose to reduce the risk of extracranial bleeding."

In October of last year, the FDA approved only the 150-mg bid dosage of Pradaxa, and the agency attempted to justify its perplexing decision by providing a not-terribly-convincing argument in an April issue of the NEJM. Beasley et al rationalized that the FDA approval "was based on our inability to identify any subgroup in which use of the lower dose [110 mg bid] would not represent a substantial disadvantage." However, Eikelboom's subanalysis provides a compelling reason for approving the lower dosage (which is already available in Canada) in the United States.