Dabigatran: Finally a substitute for the dreaded coumadin is close…

Much energy in previous posts have centered on the ablation of heart rhythm disturbances.  Navigating a GPS guided catheter through the beating heart, triangulating the source of the ectopic impulse, and then delivering a cautery-like RF lesion is fun to do, gratifying to all involved, and makes for decent writing topics.

However cool ablation is though, it is not all that a doctor of the heart rhythm does.  Despite what one can read on internet news sites, dysrhythmias like atrial fibrillation more often than not, require medical therapy.

The dreaded blood thinner, warfarin (Coumadin) comes to the fore often.  In aggregate, I have likely spent months of my life discussing the risks and benefits of this much maligned drug.  Common rat poison is made from the same ingredients as warfarin –only rats keep eating it and die days later of bleeding, while humans have the blood thinning effects modulated through frequent blood tests, called the INR.  Adjusting the INR within two-three times normal results in significant stroke reduction in patients with AF.

No drug with proven benefits has received more negative press than warfarin.  It is a difficult drug to administer, significant drug/dietary interactions exist, and the bleeding risk associated with inappropriately high INRs are substantial.  For years now, doctors and patients alike have waited for an aspirin-like pill which can thin the blood without the need for monitoring, or the worry of drug/dietary interactions.

Patients have asked, so here is a brief introduction to Dabigatran –marketed in Europe as Pradaxa.   Dabigatran is likely to be the first warfarin substitute.  It is an orally administered, twice daily blood thinner that works like warfarin, only further downstream in the blood clotting cascade.  As an inhibitor of thrombin, it slows the blood clotting process.  Stroke is the one of the major complications of AF, therefore, prevention of clots in the left atrium of the heart during atrial fibrillation is a central tenet of therapy.

(It is important to note, and somewhat counter-intuitive that a “rhythm” controlling strategy, be it ablation or drugs, has not yet proven effective in stroke reduction in AF.  The notion that preventing AF should prevent stroke is simply incorrect; primarily because no real “cure” of AF exists, yet.)

The RE-LY study, published in September 2009 in the NEJM, showed Dabigatran superior to warfarin in stroke prevention, but most importantly, there were significantly fewer bleeding episodes.  It is beyond the scope of this piece to discuss the statistical details, but suffice to say, this 18,000 patient multi-center prospective study unequivocally demonstrated Dabigatran’s superiority to warfarin in the treatment of AF.  The science was exemplary.

Other practical advantages of Dabigatran over warfarin include: blood thinning without the need for blood tests, it is well tolerated with minimal adverse effects (including no significant liver toxicity),  it has minimal drug interactions, and no significant dietary interactions.

Dabigatran is the property of the privately held German pharmaceutical company Boehringer Ingelheim.  Although approved in Europe, Dabigatran is not yet approved in the US.  It was submitted to the FDA in December with approval expected later this year.

Finally, a substitute for warfarin is close.  Yes, the drug is considered both superior in efficacy and safer than warfarin by most experts, and so, in a “perfect” system of healthcare, it should be readily available to all.  It is best for the patient, right?  

However, consider that in the socialized medical system of Europe, Dabigatran costs nearly ten times as much as warfarin.  In the US healthcare system it seems certain Dabigatran will cost much more.  Patients will have before their eyes a clearly superior drug with less bleeding risk –a substitute for rat poison.

Great news one would think, but consider the upcoming choice of costs versus efficacy and safety.  Dabigatran will cost many times that of warfarin, likely in the hundreds per month.  Will insurance companies be cajoled into paying?  Will patients pay extra?  How about Medicare?   Government tells us Medicare costs are to be reduced.  Surely not by paying 10 times more for such a commonly used drug as warfarin.  The upcoming adjudication of this superior, but expensive new drug will make for an interesting and instructive story.

Maybe the Boehringer Ingelheim people will price the drug reasonably in hopes of developing brand loyalty, so as to strengthen their competitiveness against the newer direct thrombin inhibitors that are sure to come.  For just a fantasy moment, let’s say Dabigatran cost only 2-5 times more than warfarin.  It follows that many more patients would switch, and what profit is lost on margin will be made up in volume.  No, this will never happen –forget I suggested it.   Silly thinking.  Naive.

JMM

Disclosures:  With joy, I declare zero financial relationships to any medical device or pharmaceutical company.  That is, except that turkey sandwich and peanut butter cookie I had last week compliments of the smiling youthful Boehringer Ingelheim representative who could not, and did not mention dabigatran.