Dabigatran is superior to warfarin, but at what cost?

Dysrhythmias like atrial fibrillation (AF), 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.

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, and 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.

But, no, this will never happen –forget I even suggested it.

John Mandrola is a cardiologist who blogs at Dr John M.

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  • http://thehappyhospitalist@gmail.com The Happy Hospitalist

    I thought medications were a right. Why don’t insurance companies just set the price and force drug companies to sell it to wholesalers at $4 a month. That sounds reasonable to me.

  • tom delougery

    Its important to remember dabigatran is released only for DVT prophylaxis in Europe – where the competing drugs (LMWH) cost much more – and not for therapy.

  • alex

    Worth noting that warfarin is practically free, so “ten times more” would be forty dollars a month (total, not copay). Tsk tsk, we chide the drug companies for citing relative over absolute risk and there we go falling into the same trap.

    Plus you have to factor in the elimination of coagulation clinics and reduction in close followup after dose adjustments, fewer bleeding events, less (no?) need for bridging with LMWH… the drug company isn’t going to have a hard time arguing that they can charge a boatload for this and still save money for Medicare overall. Warfarin was one of the great lowhanging fruits in medicine where any reasonable alternative was going to be ridiculously attractive.

  • mary beth dawson

    i have been working on the pharmacoeconomics of another factor Xa inhibitor, almost the same as dabigatran. Bottom line…warfarin is cheap, really cheap, like pennies. Warfarin’s adverses (stroke, ich) are generally due to supra- or suboptimal therapy…either case, although adverses are rare, they are costly. The trade-off for these novel anti-coagulants will be the better safety profile…also, index pricing in EU could be a huge factor in keeping costs down! don’t give up hope.

  • Rat

    I am sure someone will find a way to make money off my misfortune.

    “I thought medications were a right. Why don’t insurance companies just set the price and force drug companies to sell it to wholesalers at $4 a month. That sounds reasonable to me.”

    I hate the medical system. Perhaps we should sell warfarin over the counter. Then I wouldn’t be forced to pay for something that is clearly a priviledge that I cannot afford and seems to offend those who are responsible for my health.

  • Tom DeLoughery

    Dr Schulman dealt with this issue in the March 18 NEJM (Volume 362:1050-1051)

    The concern of Teachey is understandable. The price in Canada for a 75-mg capsule of dabigatran is $3.95, corresponding to an annual cost of $5,767 for the treatment of venous thromboembolism (150 mg twice daily). Currently, dabigatran is approved only in Canada, Europe, and some other countries for prophylaxis against venous thromboembolism after arthroplasty in the knee or hip, and its main competitor is low-molecular-weight heparin. The price may drop when the main competitor becomes warfarin for long-term indications. It should also be kept in mind that total direct and indirect costs for management of anticoagulation with warfarin far exceed the cost of the drug. In a recent study, the direct costs during the first year of anticoagulation with warfarin in primary care were calculated at Swedish krona 16,244, corresponding to U.S. $2,230. This does not include expenses to patients for travel to the laboratory, lost time from work, or an accompanying caregiver

  • http://notwithstandingblog.wordpress.com The Notwithstanding Blog

    I have a few quibbles with parts of this post.

    To begin, if a “perfect” system of healthcare is one that provides all care to all patients at any cost… who pays? I don’t know that a system that meets the implied standard of “perfection” here is one that is sustainable, even in the short-term.

    Next, Europe does not have a “socialized medical system.” Different countries do things differently. Yes, the UK has a “socialized” system in which the government funds and provides medical care. Switzerland has a system of managed competition between private insurance companies.

    Furthermore, I doubt the drug “costs” less in Europe. It may sell at a lower price, but the manufacturing, R&D, marketing, and administrative costs are unlikely to be dissimilar from the cost as calculated in other countries. This distinction is important: those who don’t master it are the sorts who believe that you can control health care costs by limiting the price that insurance companies can charge.

    Finally, why should the drug developers care about brand loyalty if theirs is a clearly superior product, as is argued here? Say what you will about drug companies, I doubt that they’re all managed so poorly that they would leave money on the table by grossly mis-pricing their product. If enough people are willing to pay that amount for the drug (something that they would do if purchasing the drug is a value-added proposition for them), then the price is sustainable.

  • Patricia

    its nice to find out about this drug but why do we have to always feel the pinch.I have had 3 DVT in 1 year even with the blood thinner.2 clots were all the way down both arms the 3 was at the end of the mediport for chemo…