Thursday, February 06, 2014

Genomic dosing of warfarin

Time in therapeutic range (TTR) is important for the effectiveness and safety of warfarin. TTR has been found to be poor in recent studies which in part explains the favorable profile of target specific oral anticoagulants in comparison to warfarin.

It was hoped early on that genomic testing to guide dosing would have a favorable impact on TTR and hence clinical effectiveness. But when subjected to the scrutiny of clinical investigation the field has been controversial if not disappointing.

Two recent studies recently published in NEJM [1] [2] have conflicting results and hence will do little to resolve the controversy. TTR as a whole in these studies was poor.

1 comment:

Jon said...

It seems that the differences between the two studies' findings can probably be attributed to the fact that the EU-PACT study used fixed-dosing of warfarin, while the COAG study used an algorithmic dosing approach based on a number of clinical variables known to affect warfarin response (age, ethnicity, whether the patient was also on amiodarone, etc.).

The COAG trial was very tightly controlled and from a methodological perspective was probably more sound. COAG was double blinded, while EU-PACT was single blinded; COAG included a substantial fraction of subjects of African descent, while EU-PACT had few. The degree of control in COAG is one of its few limitations; it's really only looking at the incremental benefit of genomic testing in addition to the algorithmic approach, which it did not find. EU-PACT used fixed dosing as a control, so it should be no surprise that the differences between the two groups are larger than in COAG. Given that an algorithmic approach to dosing which outperforms fixed dosing is freely available if you're willing to put in a few minutes of work, however, it's unclear to me why one would ever choose to use a fixed dosing strategy. Perhaps it might reflect how community physicians dose warfarin in practice, but if an algorithmic method can achieve the same results as pharmacogenomic testing at much less cost, then the focus should be on getting physicians to adopt that strategy.