August 2, 2014

Guest Post by Dr. John Mandrola: More Dabigatran (Pradaxa) News

Dr. John Mandrola shares a great update on the latest info regarding dabigatran (Pradaxa, Pradax). Dr. Mandrola not only treats atrial fibrillation patients, but he has also experienced afib himself.

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 imputed 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.

Reprinted from Dr. John M blog

Disclaimer: Patients come first at StopAfib.org, and we do not compromise on that. However, even though Boehringer Ingelheim, the maker of Pradaxa, has been a donor to StopAfib.org and we also partner with them in the Facing Afib program, we believe that this is important news for the afib community.

Comments

  1. I had a ‘successful’ Cath Ablation procedure to tx ‘permanent’ AFIB. It worked…normal sinus rhythm x 2 years out. It was the Pradaxa anticoagulation = Pradaxa failure, that allowed blood clot formation, and embolism, Ischemic Stroke event to occur during post procedure recovery. I suspect concurrent PPI / antacid use, interfered with efficacy, due to reduction in Pradaxa absorption into bloodstream.

  2. Carol, Thanks for sharing what you have learned.

    Pat, I’ve been told that taking Pradaxa with protein helps, and that by taking it with meals and not eating late you can more easily manage it. If that doesn’t work, then it’s time to discuss this with your doctor. Good luck.

    Mellanie

  3. I have been on Pradax three months now and the heartburn was so severe I had to go to ER twice, once by ambulance. However, the benefits are so great from being able to take an alternative to warfarin that I experimented and have found that if I take Pradax 1/2 way through my meal, no heartburn occurs. Taking the pill at either end of the meal brings hearburn on. I hope this info works for others. Carol

  4. Pat Townsend says:

    Pradaxa – just began 150/2 times per day. Had previously been on Warfarin with constant changes to stable the INR. I am experiencing SEVER heart burn. Can hardly swallow. My Dr. said I can’t go back to the coumadin. Said I should take Nexium. This is my second day of taking Nexium. Seems odd to take Nexium and then take the pill that I know is causing the heart burn. Please offer some advice.

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