Thursday, December 24, 2009

It seems very likely than warfarin's days are numbered

The oral, direct thrombin inhibitor, ximilagatran for a while seemed to be poised to be the replacement for warfarin. Early trials indicated its efficacy and safety (at least in terms of bleeding risks) but its further advancement was stymied and ultimately blocked by the observation of what proven to be a unacceptably high level of abnormal liver function test abnormalities.(Direct thrombin inhibitors (DTIs) block thrombin from cleaving fibrinogen to fibrin.)

However, its descendant, dabigatran has successfully made its way through two large randomized clinical trials and seems to be at least as efficacious and at least as safe (in terms of bleeding risks at and no major signals of other adverse effects) and will probably emerge as the long sought after replacement to warfarin.

First dabigatran looked good (in some outcomes better than warfarin and in others, "not inferior") in the RELY trial which studied its use in high risk patients with atrial fibrillation. Next the RE-COVER trial (this is not to be confused with the RECOVER (without the hyphen) trial) compared dabigatran with warfarin in patients with deep vein thrombosis and found similar good results.

So far,dabigatran seems as efficacious and safe as warfarin in atrial fibrillation and in DVT and does not require frequent blood test monitoring nor frequent dose adjustments.

Still there are concerns and questions. Dabigatran is given twice a day so the compliance issue has to be considered. Further,in RELY two doses were tested. At the 150 mg twice a there were fewer strokes so that dose seems more efficacious. At the 110 mg dose there were fewer instance of hemorrhage, so the lower dose seem safer. The 150 mg twice a day dose was used in the RE-COVER dvt trial so that dose may become the one generally used.

Dabigatran is approved in the EU for prophylaxis in total hip and total knee replacements and also in Canada.
2010 will probably see its approval in the U.S, fifty years or more after warfarin was approved.

3 comments:

Anonymous said...

Would be interested in you also always comaparing costs (if known) when you make these obsevations.

Respectfully,
Curt Sandberg
Anaheim, CA

james gaulte said...

I have no data for US prices but I'll bet dabi will cost more per pill,but I suppose you have to factor in the cost of many INR determinations.Actually the Wikipedia site says that dabigatrin costs about 10 times warfarin for the NHS in Great Britain.

Anonymous said...

if dabi costs $5 a day while warfarin is 10cents, a protime is $5 once a month. the most overhyped drug since Multaq!