More Dabigatran (Pradaxa) news

I have become an AF-doctor. That means my most exciting aspect of medicine is terminating AF with watts delivered through a catheter. “Got it.” In that beautiful moment, the take-the-fun-out-of-medicine people seem far away. Huge grin!

Though all that high-tech stuff is exhilarating, it’s fair to say that the most remarkable thing in AF medicine today is the novelty of thinning the blood with a pill that isn’t rat poison.

The dabigatran (Pradaxa) phenomenon continues at a fever pitch.

Only three weeks have passed since my last update, and there is already more to say on a number of recent dabigatran publications. In addition, I’d like to tell you about a case that changed the way I speak with patients about taking the new blood-thinner.

Dabigatran Effect by AF type:

There are three types of AF: paroxysmal (self-terminating), persistent (requires a shock to terminate), and permanent. Though it would seem intuitive that stroke risk would be higher in more advanced AF (permanent), this has not been the case for warfarin-treated patients. Warfarin reduces the risk of stroke irrespective of the type of AF.

Does dabigatran behave similarly?

This was the question asked by a group of researchers who looked back at the 18,000 patient RE-LY trial—medical speak would call this kind of trial, subset analysis. As presented in abstract form at last week’s American College of Cardiology meeting, the RE-LY investigators found that the twice-daily 150 mg dose of dabigatran was equally effective in all forms of AF. (A nice summary can be found here at theHeart.org)

Interestingly, the lower dose (110 mg) of dabigatran appeared less effective than the 150 mg dose in more advanced forms of AF, though the difference didn’t reach statistical significance—meaning that it could be due to chance. For US doctors, the effect of the 110 mg dose of dabigatran is a moot point, since the FDA has approved only the higher dose.

Dabigatran 150mg vs Dabigatran 110mg:

The FDA decision to approve only the higher dose (150mg) of dabigatran has been a matter of some debate. Last week, in the NEJM, three FDA officials published a clearly written explanation why they approved only the higher dose. They point out that the slightly lower-bleeding risk of the 110mg dabigatran dose didn’t outweigh its lesser effect in preventing strokes. They specifically looked at three high-risk subgroups that might benefit from a lower bleeding risk: the elderly, those with impaired kidney function, and those with prior bleeding. In all these groups the 150 mg dosage bested the 110 mg dose.

Their analysis rested on the assumption that a major stroke is worse than a bleed. I believe this to be entirely true—as a stroke is frequently irreversible and life changing, whereas more often than not, a bleed is not. (For non-NEJM subscribers, Larry Husten has a nice summary on his blog, Cardiobrief.)

Dabigatran Cost:

Another ACC abstract that concerned dabigatran addressed the important issue of cost. This trial of 1774 patients (from the Brigham and Women’s Hospital) assessed the cost implications of switching eligible patients from warfarin to dabigatran. In their warfarin clinic more than 90% of patients were deemed eligible to switch.  On one side of the ledger, the Boston researchers placed the costs of warfarin, including its INR-monitoring, and on the other side, the costs of dabigatran, which of course has no need for monitoring. They were surprised to find that dabigatran nearly tripled the expense. The savings from not having to do INR-monitoring with dabigatran didn’t come close to balancing the high cost of the drug.

The most important critique of this study was that it was not a true cost-effectiveness trial. Unlike this Annals of Internal Medicine trial, these researchers did not look at the tremendous cost-savings of reduced strokes and intra-cranial bleeding. To show cost-neutrality of dabigatran, considering its lower number of strokes will be critical. We can all agree that the costs of stroke care are enormous.

Though you can quibble with the fact that the Boston researchers inputed a very high cost (358$/month) for dabigatran, the take home message was that avoiding INR testing does not balance dabigatran’s high cost. That’s important information for the real-world patient, as it dispels the commonly cited notion that not having to do INR tests will balance the high cost of the drug.

And, more interestingly, it remains to be seen how much people will pay for dabigatran’s unrealized statistical benefits in future stroke prevention. What is the real-world out-of-pocket value of a more favorable hazard ratio?

An enlightening case:

Finally, a specific case of a dabigatran-related adverse effect has caused me to slightly revise the way I present the pros and cons of the new drug to patients. The case involved an older man who developed severe reflux symptoms a week after starting dabigatran. His primary care doctor said the symptoms were bad enough to warrant a GI consult. He suffered terrible pains, thought not possibly related to the drug. Astutely, the GI doctor simply held the dabigatran and the symptoms abated. No unnecessary procedures were done, and the patient recovered with one of medicine’s best remedies: a tincture of time. (A thinking GI doc is a real friend to an AF-doc.)

I used to tell patients that one in ten patients on dabigatran get heartburn. Now, after this case of severe upper GI symptoms, along with a number of other less severe heartburn cases, I am going to tell patients that one in ten patients really do get heartburn, but I’ll emphasize that the pain could be very significant.

The real-world learning curve for dabigatran continues.

Stay tuned.

JMM

PS: I have declined offers to be a Boehringer Ingelheim thought leader. I have no industry relationships to disclose. I’m just a blogger.

Comments

  1. Jay says

    Thanks for all the info. Keep it coming. Nothing is ever what it seems right out of the gate.

    Around here in conservative Cincinnati, we try to let guys like you work out all the kinks surrounding new stuff.

    New stuff scares us folks. :)

    Lucky for me, most people are not asking for Pradaxa, so I can proceed at my own pace. Mostly, I’ll use it for new anticoagulation indications. We’ll also convert those who are difficult to regulate and those who complain loudly about INR draws.

    Jay

  2. Ronald H says

    “Astutely, the GI doctor simply held the dabigatran and the symptoms abated. No unnecessary procedures were done, and the patient recovered with one of medicine’s best remedies: a tincture of time.”

    Wait a minute— this patient was in A fib and I presume he needed anticoagulation. So simply holding the medication without any thought to the reason the medication was prescribed is not good medicine. If he was really astute, he would have picked up the phone and called you and asked what alternatives to anticoagulation were available.

    • says

      RH,

      Thanks for writing.

      Your astute observation highlights one of the downsides of a blog post–brevity. (Most people will not an read excessively long post–at least I won’t.) But at the same time your comment brings out the coolest part of “new media,” that is, the conversation part.

      In the ‘comments’ section, I can tell you more about the case: The GI doc did pick up the telephone. He called the family doctor, and agreed that switching back to warfarin was the right move. They rightly agreed that a few days off blood-thinner seemed appropriate–given the fact that a “scope” may have been needed if the symptoms failed to pass. The primary doctor had called me to inform me of the situation.

      Also, another fact that was not stated in the original post was that the primary care doctor was informed, and involved in the original decision to start dabigatran. All this phone communication sounds old-fashioned, but some would argue that it was the reason why the patient was cared for so well.

      Another important point here that isn’t talked about much, primarily because there exists little data, is that in AF patients without mechanical valves or a previous history of stroke, transient interruption of blood-thinning for a few days confers little risk. The benefit of blood-thinners in patients with AF is measured over many months (to years), not days.

      The point of the case was to highlight that, unlike warfarin, dabigatran can cause significant GI symptoms. Imagine if every doctor knew that fact. Think of all the unnecessary testing and procedures could be avoided. Knowing helps; It’s the same concept of knowing that a young, healthy patient that passes out after hitting their thumb with a hammer doesn’t need thousands of dollars in MRIs and EEGs.

      Wow, I’d better stop typing. Mine wasn’t a very brief response.

        • frank says

          if you’re on medicare with, if it’s correct, it’s a $ 40.00 per month co-pay. ( according to my pharmacist) so by 12 it’s $480.00 a year not bad but if you have no medicare or insurance coverage, at about $ 250.00 per month times 12 it’s $ 3,000.00 a year. not worth it to me thats why i’m starting off slow. even with medicare if have other expensive medications adding $250. a month will get me nto the doughnut hole quickly and then all the prescription come out of your pocket. we all have to do our own math about pradaxa. i suppose it’s a ty it and decide if it’s worth it to you. it’s not that we cain’t go back to coumadin if we decide pradaxa is not worth it for us.

        • says

          Linda,

          That’s the 64K question, and it’s also a very personal decision. Better stroke prevention–how much is that worth? How about fewer catastrophic brain bleeds–and that in dollars?

          Then, there is the convenience of not driving to the doctor’s office, waiting in line, pricking your finger and adjusting a warfarin dose. The worth of that?

          If these aren’t hard enough questions, then add in the notion of risk. Obviously, the higher the risk of stroke (CHADS Score), the more statistical benefit from the drug. But of course, not all high risk patients have strokes, and not all low-risk patients avoid them.

          These issues are only the tip of the iceberg.

          Stay tuned…

  3. Sandy says

    What the researchers failed to add to the cost of warfarin is the time spent sitting in some lab waiting room. Not everyone taking this drug is retired; some of us have to go to work, and work time lost in a waiting room has to come out of some other part of our day. Economists know this has a cost. And, there’s the pain of weekly sticks, for those of us who never maintained the magic number, even with the most rigid diet restrictions. For those of us who can stomach it, Pradaxa is a blessing. I am fortunate to have health insurance that helps cover the cost. I will never go back on warfarin.

  4. frank says

    starting april 25th, i’ll start pradaxa ( 150 mg twice a day ) by then i’ll be in the legal range to start. i’ve been self testing for inr for about a year and 1/2 and have confidence in the results. once a month i’d do a self test and then go asap for a blood draw to compare lab. results to my self test. they have always been within a tenth or two. i’m 72, diabetic ( type 2 ) with about an 6.3 a1c. i’ve got a love hate thing with warfarin. love it for the life saver it is. but don’t like the self testing / lab draws / food restriction etc. what i’d like to know is there any blood work that can be done to confirm that the pradaxa is keeping my blood thin enough. my inr range was 2 to 3. i understand that inr will not tell me if blood is not forming clots when taking pradaxa. what other testing will give us indication, that we’re doing ok ?

    • says

      There is not any available test that measures the blood-thinning effect of dabigatran. But know this: in the 18,000 patient RE-LY trial, 12,000 of whom took dabigatran, there were fewer strokes and less intracranial bleeds.

      It’s a new way of thinking, but what I tell my AF patients is this: if they take dabigatran twice daily, their blood is thin enough to prevent more strokes than warfarin-treated patients.

      The question of how much better dabigatran is when compared to patients with home INR monitoring that absolutely insures ideal blood-thinness is a good one, and is still a matter of some debate. That study hasn’t been done.

      Stay tuned.

  5. says

    When I first started Prodaxan I had terrible stomach problems and heart burn. Ater a couple of
    days I decided that if I had those problems for one more day, I would go back to coumadin. It
    did lesson and finallly quit and I woud not go back to coumadin.

    • says

      Thanks for sharing. See, now I have learned something from the blog. In using dabigatran for five months, that is the first time I have heard a person say the heartburn may disappear over time.

  6. Fred Ehlers says

    I started taking pradaxa 2/8/11 after 5 yrs. of warfarin.The first or second day I took it, I had heart burn bad and it kind of scared me. After that, only once and it was very mild, no other side effects. I take 150mg bid. In regards to the price my insurance pays $187.00 a mo. and I have a $20.00 co-pay. I am 75 yrs old. I get most of my info from you. Thank you very much.

    • frank says

      hi fred. & dr john i’m starting mine monday. in warfarin withdrawel right now. my wife says i’m imagining things: but when i do my finger sting to get a drop of blood to test my sugar level it seems the little drop i need takes longer to appear and seems darker and thicker. hope i make a trouble free transition to pradaxa. glad you’re adjusting with no problem. i’m starting off with a 12 day/ 2 a day /150mg supply in blister packs. the thought is that if there’s a problem it will show up within that time. i have not filled my prescription until after i see how i do. with the free start up ones dr. gave me. do you get yours through the medicare drug coverage ? thanks all

  7. Fred Ehlers says

    Frank, no it is not through medicare coverage. One other thing when you pick up your prescription make sure it is in the original bottle.

    • frank says

      thanks fred, for the advice and the insurance info. i’ll be reporting on my progress as i make the transition.

    • frank says

      your cardio. may have sample packets on hand. they are for a 6 day supply @ 2 a day it’s a start to at least get an idea if you have any reactions. . if you’re on medicare it’s approved by them as of this april 1st with a copay of about $ 40.00 for a 2 a day 30 day supply. call 800-542-6257 option 4 and you’ll be put through to a registered nurse or a doctor. the nurse i spoke with was very helpful.

  8. frank says

    when i spoke to the patient help nurse at boeh…….
    i asked if there were any test that would give an indication of how well pradaxa is ” doing its thing ” he mentioned; E.C.T and also T.T. blood work i don’t know if these are different names for the same thing or different tests. for those of us who need to wean from the draw needle do these help dr. with monitoring us or not. thanks.