The first four months of a new era.

My iPhone vibrated with an urgent message that read:

Please call…The INR on your atrial fibrillation patient scheduled for cardioversion is too low.  He is on that new blood thinner, Pradaxa.  What do you want to do?

I responded, sounding like an expert:  “It’s Ok.  Pradaxa thins the blood adequately, it just doesn’t change the INR.”

She astutely responded, “How do know the blood is thin?  What if the patient doesn’t take the medicine faithfully?”

“Hmm?”

In the treatment of atrial fibrillation, this exchange illustrates a sea change in thinking.

Until only four months ago, the only way to prevent stroke in patients with AF was to use a rodenticide.  No one likes warfarin (Coumadin).  Doctors don’t like it because of its variable effects, risk of under or over-treatment, and multiple drug/dietary interactions.  In the best case, in closely supervised clinical trials, warfarin-treated patients are in therapeutic range only two-thirds of the time.  Patients dislike warfarin because of the hassle of frequent INR measurements, and because they are scared to take a drug which can cause excess bleeding.  Who wants to take a rat poison?

Heart rhythm doctors-in-training will start their practice hardly knowing the enormity of this change in blood-thinning practice.  Us seasoned doctors have toiled with warfarin for the entirety of our career.   It’s hard to put into words the anticipation (and surprise) that dabigatran brings.

Here are a few of the many upsides of dabigatran:

  • It replaces warfarin, a drug whose downsides are legion.
  • The science supporting dabigatran is stellar.  The 18,000 patient-strong RE-LY trial clearly showed that—for AF patients—dabigatran is a better blood-thinner than warfarin. Dabigatran-treated patients had fewer strokes and less intracranial bleeding than those who took warfarin.
  • The novel way in which Dabigatran thins the blood means that INR testing is not needed.
  • The metabolism of Dabigatran offers patients many useful advantages.  Unlike warfarin, there are no significant drug or dietary interactions.  Patients can drink cranberry juice and eat salad to their heart’s content.
  • The rapid onset of dabigatran’s blood-thinning effect allows for shorter hospital stays.  In the past, rightly or wrongly, common practice held that patients stayed hospitalized on IV (or subcutaneous) blood-thinners for the three-five days that it took warfarin to adequately thin the blood.  Dabigatran shortens this multi-day kabuki dance to hours.
  • Dabigatran is cost-effective.  This Annals of Internal Medicine trial suggested that although the drug costs more upfront, its convenience (no INRs), superiority and better safety profile pay off in the long run.

That’s a lot to like.  But of course, dabigatran has some downsides.  These include:

  • For most patients, it costs much more than warfarin.  Patients need to ante-up more of their money.  How much they are willing to pay for the convenience and superiority of dabigatran remains to be seen.
  • It’s a twice-a-day drug.  Many experts are rightly worried that the compliance of real-world patients may be less than the RE-LY cohort.
  • One in ten patients who take dabigatran get heartburn.  Warfarin doesn’t have any of these nuisance side-effects.
  • Dabigatran is cleared by the kidneys.  Patients who have (or develop) kidney disease require dosing adjustments.
  • The un-measurability of dabigatran makes doctors nervous. We are still getting used to the foreign notion of not knowing whether the blood is thin.  With warfarin, the standardized INR measurement provides assurance that the blood is thin.  With dabigatran, on the other hand, whether the blood is thin depends simply on whether the patient actually takes the medicine.  This issue isn’t a small point.  Consider the above vignette on cardioversion.  To protect patients from a dislodged blood clot, the current protocol before cardioversion mandates three weeks of adequate blood-thinning with warfarin, the adequacy of which is confirmed with serial INRs.  With dabigatran, there exists no such measurement.

So, what am I doing (or seeing) with dabigatran?

I guess you could call me a cautious early-adapter.

I started using dabigatran slowly.  It’s not just another new medicine; it’s a paradigm shift—a sea change.  The water is cold and the waves strong; I am dipping my toes before plunging in.  Remember, the last non-generic medicine heart rhythm doctors saw was Multaq.

My approach to Dabigatran is to discuss its risks, benefits, alternatives and expectations.  This includes the drug’s newness.  Then, each patient decides whether to take the drug on their own; that’s called patient-centered care.

Thus far, most patients look favorably on dabigatran’s obvious positives, but whether they switch depends mostly on how much of their own money they have to part with at the pharmacy.

I also emphasize the fact that dabigatran may be especially helpful to AF patients with multiple risk factors for stroke (diabetes, heart failure, previous stroke, high blood pressure or age greater than 75), or in those with difficult to control INR levels.

Discussing all of AF treatment in a single office visit is a challenge.  Dabigatran makes this task harder.  The novelty of how it works, the newness of the concept of a non-warfarin blood-thinner and the complexity of discussing clinical trials has added even more complexity to the already complex typical office visit for AF.

I recommend dabigatran only for patients with non-valvular AF.  Though it will likely prove effective for many other diseases that warfarin is currently used, it’s clearly too early to venture off-label.

In the first four months, I have yet to see a major bleed with dabigatran.  A couple patients stopped the drug because of heartburn.  Many more declined because of cost.

In summary, my very early real-world experience with dabigatran looks encouraging.  No doubt, there remains much to learn.  It’s a great time to be an AF-doctor.

Stay tuned.

JMM

Disclosure:  I am not a paid thought-leader. I have no relationship with the makers of dabigatran, Boehringer-Ingelheim, or any other pharmaceutical or medical device company.

Comments

  1. Rich says

    My mom just had her first bout with affib yesterday just before a stress test. I quickly educated her on this new drug and they started her on it yesterday. After personally having to deal with the Rat treats I am very happy for her that this new drug is available.

      • Rich says

        The $160.00/month price tag is a little overwhelming though. But she is going for it as she is to only be on it for the short term. The Doc also gave her a months supply to get her started.

  2. anon says

    the blister packs may help you to assess compliance with this medication.

    how many doses missed will result in nontherapeutic levels? we have decided for the time being to TEE these patients when cardioversion is planned. i would be interested to learn what your strategy is.

    also how long do you overlap with lovenox when initiating dabigatran? also how are you incorporating into afib ablation plans pre and post?

    • Dr John says

      Anon,
      Good questions.
      I have yet to use dabigatran pre or post ablation. I don’t plan to do TEEs routinely.
      And compliance will prove hard to document–at least at the moment. That patients are responsible for taking the medicine, or reporting that they didn’t is an interesting concept, don’t you think? A kind of paradigm shift.
      Thanks.

  3. PGYx says

    Thanks for sharing your from-the-trenches experience with dabigatran! Prior to dabigatran approval, I cared for a patient on the drug who presented with moderate acute renal failure, INR ~7, and non-life-threatening but still significant spontaneous bleeding.

    As an intern, I care for enough elderly people with both atrial fibrillation & acute renal failure that I wonder if I should expect to see more patients with a similar presentation. Do you think this is misplaced worry or valid concern?

  4. Bethany says

    I have been on coumadin for a year now, and before then I was on heparin three times a day. I am only 19 years old, but keeping a stable INR for me is hopeless. Its been a year now, and I go from 1.2 – 4.0 but I am usually on the lower end. My doctor called me today and has decided to switch me to Pradaxa. I am always very scared my blood is going to get too thin. How will they know if this new medication is going to make my blood too thin, if I never go for testing? I have been getting my INR checked once a week, and although inconvienent, it kind of makes me feel at ease that I know I am not at risk for serious bleeding.

  5. Nick says

    Hey Bethany… Can you name the reason you are beeing on Coumadin? Cardial problem or clot protection like APS? (Antiphospholipid Syndrom)? The reason I am interested to learn from many people is that here in Greece the new medicine has also authoraization but phisicians are sceptical in prescribing it for chronic conditions like APS. My wife is 28 years old and in warfarine since she was 22. As you can realise we both expecting to improve both her safety and life ease through the new medicine. Please, right here if you have heard anything for this kind of treatment.

  6. Lisa rose says

    Thank you for this site, doctor John. I am 72 year old on 6 years of Plavix for 5 DES stents. Have had erratic HRates with 10 second lightheadness for 5 years. Finally a recent 30 day event monitor picked it up. Doc called last week and said Atrial Flutters in upper chamber and come see her. She gave me an RX for Pradaxa and told me to get off Plavix. Filled the pradaxa at a 50.00 co-pay )-: (still have private insurance as hubby is still working)
    I was never told of alternatives or side effects…This was a wonder drug, she said. Bottle is still sitting here unopened. I put the cart before the horse. I do not want to be off Plavix with FIVE Drug Eluting Stents. Three in the RCA and 2 in the LAD. One MI in the distal apex. Called another doctor and he said NO..cannot get off Plavix with five DES STENTS. Coumadin? No…Do not want that either. I want to see an Electropheisis doctor for an ablation. Am I asking for too much. Lovenox? Is that a good choice. Can’t my .375 Bayer and Plavix be some help for blood thinning? Echo’s show moderate Mitral stenosis. I also have a gradient with LVOT..not high,,(20-25) and Diastolic Dysfunction and an on and off murmur is heard. Not a happy camper right now. I need advice. Thanks…Lisa Rose…a YOUNG 72 year old.

    • Dr John says

      Lisa,

      Yours is a complicated situation. I can agree that seeing an electrophysiologist is a good idea. Other than that, it would be very dangerous for me to give any specific medical advice.

  7. Sam Mapes says

    “I recommend dabigatran only for patients with non-valvular AF”
    Dr.John; My doctor put me on Pradaxa even though I have AF with mitral valve prolapse.
    He told me that the AF was most likely caused by the MVP.
    Two questions: 1. Why is Pradaxa only recommended for non-valvular AF?
    2. I will be having open heart surgery in May to repair posterior leaflet of mitral valve. How soon before surgery do you think the Pradaxa should be stopped and how soon after resumed? Thank you. Sam

    • Dr John says

      Sam,

      Pradaxa is only approved for non-valvular AF because patients with “severe” valvular disorders (or mechanical valves) were excluded from the 18,000 patient RE-LY trial. The investigators were somewhat nebulous in what exactly constitutes severe valvular disease, but I can say that historically-speaking non-valvular AF usually means the same thing as non-rheumatic AF. Currently, there are dabigatran studies enrolling patients with valve-replacements and most of us believe that dabigatran will be equal to, or better than, warfarin in these patients as well.

      I would ask your surgeon how many days he (or she) would like you to be off Pradaxa. In general, in patients who clear the drug from their body at the normal rate–those with normal kidney function– the blood thickens to its normal level 24 hours after the last dose of Pradaxa.

  8. Nick says

    Hello Dr John!
    Can you please also state your opinion about pradaxa for clot protection against APS? Do you have any similar cases heard yet? As I told you above it would be great information for us. Nick

    • Dr John says

      To the best of my knowledge, there are no randomized clinical trials of dabigatran’s efficacy in APS. Theoretically, Pradaxa should work as well as warfarin, but we just don’t know.

      Currently, in the US, Dabigatran is only approved for stroke prevention in non-valvular AF.

      There are ongoing trials looking at the utility of dabigatran for other indications. Stay-tuned.