Amen.

 You are spot on.

 Warfarin despite it's tremendously advantegous role in thousands of patients all these decades has always been an extremely slippery customer.

 A replacement has long been overdue.

Good review!

Just a minor correction. I think you meant to refer to DaVinci's Helicopter, not Rembrandt's.

Regards,

Mohamed Rahman

Mohamed,

When I went to bed last night, I suspected I had written Rembrandt's name.  Don't know why I did that.  I've actually seen Davinci's burial site, his helicopter drawings, etc.  I'm blaming everything I did yesterday on jet lag!!! Thanks for reading AND the correction!!!

Melissa 

Mohammed,

Thanks so much for your correction.  I've actually seen DaVinci's burial site, toured one of the castles he designed and have seen his drawings (of that helicopter!) I'm blaming everything I did yesterday on jetlag!!

Thanks for reading!!!

Melissa 

Well articulated. But a long to go yet.Also fine prints will be intersting. Patients who achieve target INR 79% time on warfarin do as good!!! Also the matter of daeth 1in 6000. We would certainly be happy to see end of warfarin though.

I had to laugh at your quote that "money will be saved."  I have a feeling dabigatran will be several orders of magnitude more expensive than warfarin (even including monitoring) to the point where many patients who could benefit from it will not have access.  This is a multi-billion dollar drug, and the pharma guys plan on milking that cow for all its worth.

I propose another possibility: warfarin and INR monitoring will continue to coexist with dabigatran, at least until Medicare starts regulating drug costs as it does physician charges and hospital charges.  Perhaps dabigatran will be reserved for some warfarin patients: the ones in whom warfarin is unpredictable or ineffective.  I would propose that this is the minority of patients.

Perhaps you or some other enterprising cardiologist would even take the liberty of performing a clinical trial, comparing dabigatran in patients with VKORC polymorphisms,  with warfarin in patients without these mutations.  Now that would be interesting.

The king is dead, long live the king.

 

InteractMD.com

I attended a conference recently in Boston - The North American Thrombosis Forum - where the results of Rely were presented. There was enthusiasm about the potential clinical application of this anticoagulant but also some reservations. During the Q&A period it was pointed out that point of care INR testing and genetic genotyping are tools that can help improve safety and that it is possible to maintain patients within  therapeutic range 80% of the time. It so happens that at that level of performance both products are equivalent! I can not help but wonder what would have been the bleeding rates of the warfarin arm if genotyping would have been used to identify carriers of variants and define the right dose right from the start (warfarindosing.org)given that 50% of the patients were new to anticoagultion and that most bleeding occurs during the first 30 days. The results of the ongoing COAG trial will set the bar for dagibatran and other new agents looking to replace the very effective warfarin. The cost-effectiveness issue will be no doubt be significant given the size of the patient population.

but what about this MI business? should we sing victory songs yet.............?

Appreciate all of your comments and are all points well taken.  I, too am concerned about how expensive Dabigatran will be as it comes out the gate.  We'll see if the pharmaceutical industry will be smart enough to take the market with competitive dosing or isolate itself amongst the elite patients who can afford anything they need.  Only time will tell.

As for MI risk, it was a small signal and not statisically significant and hopefully that is the way it will stay. 

Melissa

I am A Guatemalan Cardiologist,  Dabigatrán hasn't reached us yet. local Boehringer Ingelheim warriors say it´s beeing released according to FDA approval, and local beaurocratic sliding.  I think this is a great molecule, and the possibility of seeing warfarin stepping down in our country is feasable only if prices with warfarin are cost/effective anything but similar.  I doubt that very much, since many or probably most warfarin users in our country are on the low side of the economical bench.  But nevertheless I think it is about time, we all have something else besides the coumarol derivates.  I hope the dabigatran prosthetic valve issue is resolved in the following months or years.

Nice article, keep on trucking !!

Mario Lambour MD.  

Mario,

thanks so much for your post.  I have several friends who are nurses who totally love Guatemala. Saw some beautiful pictures of your country just last week.

I believe the enthusiasm is justified.  I'd use it in a heart beat (especially if it's irregularly irregular! )

Melissa

Sure, RE-LY will cost much more than Coumadin, but its use will offset the thousands of dollars per year for each patient's INR testing -- not to mention the cost of people's time and inconvenience of testing. If the economics didn't make sense then I think the manufacturer would face push-back.

As for the safety of RE-LY, I think the jury will be out until around 50,000 patients have tried it, just in case there are rare adverse events. Remember, warfarin has been time-tested by millions of patients.

can the dosage for dabigatran be clarified...referring to the RE-LY study. Was it 110mg twice for a total of 220mg or is it 110mg twice a day for 55mg each dosage. 

In case anyone is still tracking this dialogue, I thought I would point out that we have a fairly extensive critique of the RE-LY study on ClotCare.org at http://www.clotcare.com/dabigatran_vs_warfarin.aspx  Also discussed in that posting are recent studies that have improved anticoagulation management through INR self-testing and automated online management.  This approach allows patients to test their INR at home, while traveling, or anywhere; and online management required less than 10 minutes of clinician time to manage 4 "virtual clinic visits" per month.  In 2 of 3 such studies, the INR time in range improved to approximately 80% - which is substantially better than the to 50% of warfarin-treated patients in the RE-LY trial (see next paragraph).

 Also, information recently presented by L. Wallentin (see wallentin, L. www.theheart.org/article/1046957.do) examines event rates based on the patient's individual time in the therapeutic range (ITTR).  If one compares the data presented by Wallentin with the findings in the original publication, it appears that the 50% of warfarin-treated patients whose INRs were in range more than 67% of the time actually had fewer events than did patients in either dabigatran group.  It would appear that the composite endpoint of stroke, systemic embolism, MI, PE, death, and major bleeding was 5.3% per year in the top 50% of warfarin-treated patients, but was much higher at 11.9%/yr for the bottom 25% of the warfarin treated patients whose INRs were in range < 53% of the time.  The composite even rates were 7.09 %/yr and 6.91%/yr in the 110 mg and 150 mg dabigatran groups, respectively.  Those number would suggest that the number needed to treat to prevent one major event compared to the bottom 25% of warfarin-treated patients would be 15 for warfarin-treated patients with a ITTR > 67%, 21 for the 110 mg dabigatran regimen, and 20 patients for the 150 mg dabigatran regimen.  It would appear, therefore, that well-managed warfarin (individual time in range > 67%) was better than either dabigatran arm.

Perhaps the ease and efficiency of INR self-testing with automated online management together with the remarkable improvement in INR control will allow us to improve patient outcomes, reduce health care cost, and cancel the warfarin funeral.

 

 

Henry,

I think Coumadin will still be the only option for many for quite some time.  Still yet, you never know a compound until it's been on the American market for about 2 years and we might learn of issues that haven't quite made it to the forefront during clinical trials with the direct thrombin inhibitors.  However, if you had a choice between just swallowing a pill or sticking your finger once or more per week and then swallowing a pill after checking an algorithm, which would you prefer?

 The problem is that even tracking daily INR's in the hospital setting, one day it will be 1.7 and the next 2.5 and even after holding it, the next 3.2 for some folks.  

I think I'll pick out the casket and a few favorite songs just in case! HA!

Seriously, I get your point and an excellent one and thanks for posting!

Melissa