The new blood thinners and personal accountability

I recently came across a very important blog post on the use of the novel new blood-thinner, dabigatran (Pradaxa).

Fellow Kentucky cardiologist, and frequent TheHeart.org contributor, Dr. Melissa Walton-Shirley wrote this very detailed case presentation involving a cantankerous non-compliant rural patient with AF (atrial fibrillation) that sustained a stroke while “taking” dabigatran.

Dr. Walton-Shirley details the very commonly done procedure of cardioversion (shock) for AF. As she clearly points out, the most important safety feature of shocking AF back to regular rhythm entails adequate blood thinning before and after the procedure. Thin blood prevents the possibility of clots dislodging after restoring normal contraction to the top chambers of the heart (atria).

Herein lies the rub with dabigatran, and the two soon-to-be-approved non-warfarin blood-thinning agents, apixaban and rivaroxaban. In the past, with warfarin, the doctor was responsible for confirming a patient’s compliance. This task was easy on the doctor: patients come in for weekly INRs before and after the shock. If an inadequate INR was found, the procedure was postponed. Responsibility was squarely on the doctor.

But the irony of the new blood-thinning drugs is that their most attractive feature, convenience of not needing frequent blood tests, shifts the burden of responsibility to the patient. Because these new blood-thinners do not reliably affect any measurable blood tests, the doctor cannot know whether the patient has had an adequate period of blood thinning before (or after) shocking the AF back to rhythm. Only the patient can know. In a RE-LY sub-study, cardioversion with dabigatran was found to be safe, but these were study patients, not cantankerous patients that “a secretary had to deploy the National Guard to locate.”

In Dr. Walton-Shirley’s case, she took the patient at his word: that he was taking dabigatran before the shock. But after he suffered a stroke less than 24 hours later, both circumstantial and real evidence suggests that he was non-compliant with his regimen of dabigatran. Fortunately, the patient recovered well from his stroke, albeit with a rocky course.

Dr. Walton-Shirley goes on to dissect the case. She writes about three lessons that could be learned in this case. It’s an important discussion.

Role of TEE (trans-esophageal echo) before the case:

She mentions the possibility of searching for a clot inside the heart by doing a TEE before the shock. The problem here is that doing a TEE means sedating a patient and sticking a very large rigid black tube into the esophagus. This far from non-invasive procedure is not needed in patients who have adequate blood thinning before the shock. In her case, the patient ended up with a severe complication from a TEE at an outside institution. She rightly concludes that TEEs are not the answer to confirming patient compliance.

Role of measuring the PTT (a common measure of blood-thinning) pre-shock:

Though it is true that patients that have taken dabigatran the day before the procedure have elevated PTTs, it does not in anyway confirm that the patient was taking the drug for the prior 3 weeks. Nor does it imply the patient will take the drug after the shock, which is of equal significance.

The general concept of using dabigatran in patients non-compliant with warfarin:

After this case, Dr. Walton-Shirley writes, “I will never utilize dabigatran in a patient with a history of poor or marginal compliance, because even if their PTT is adequate at the time of cardioversion, there is no guarantee they will be taking it regularly in the future or that they’ve been compliant with it consistently.”
Few could disagree with that statement.

I commend Dr. Walton-Shirley for writing such an important case report.

My comments on the case are as follows:

The new paradigm that these novel blood-thinning drugs have created represents a seismic shift for doctors and patients. For doctors, we have to decide, no, call it judge, perhaps even trust, that our patients will comply with taking an expensive drug that makes them feel no differently.

Doctors vary in the degree that they mother patients. Some will send the National Guard to locate a patient to get them into the office for their care, while others are of the ilk that think a patient needs to accept at least enough responsibility to get to the doctor’s office for routine care. They take the view, if a person can afford 12$ per day for cigarettes, they can afford a ride to clinic. This notion of mothering will have a lot to do with how a doctor uses these new drugs. Do they want the responsibility (of confirming INRs), or is it okay for the patient to be responsible (for taking the drug as directed)?

Ultimately, preventing strokes with potent drugs that patients must take as directed, and doctors cannot confirm that they have done so, highlight three important criteria for good outcomes with any medical treatment:

  • The critical role of patient responsibility for their own health. Non-warfarin blood thinners place the onus on the patient. The conveniences of these drugs come with a hefty price: personal accountability.
  • The ever-important communication skills of the doctor in explaining the concepts of these novel drugs.
  • The requirement that doctors exercise sound judgment in deciding whether a patients can garner benefits from this very new paradigm of therapy.

It’s an exciting time to be an AF doctor.

Thanks to Dr. Walton-Shirley for sharing such an important case.

JMM

11 comments

  1. thanks for the article. i’ve been on pradaxa for 3 months and have been a 5 star patient. i follow the blog everyday and this is the first pradaxa article in the longest time. was starting to think pradaxa had become a no-no subject. thanks for bringing it back. you are appreciated for the insights and wisdom you bring us all. no short cuts to any of this just ” stay with the program ” thanks

    1. Hi Frank.

      No, Pradaxa is not a no-no topic. Thanks for the kind words.

      I wrote this piece because the initial spike of Pradaxa excitement has cooled a little. The concern over costs, patient compliance, uncofirmability, and also the GI intolerance issues have all combined to dampen enthusiasm a little. Like Dr. Walton-Shirley said, dabigatran clearly has its place in the treatment of AF, as it offers some patients an incredible efficacy benefit as well as convenience. But there are significant limitations, not the least of which is the learning curve for both patients and doctors.

  2. if the patients are noncompliant, are they safer with warfarin? are they safer with nothing?

    1. Medicines like blood thinners have what’s called a “narrow therapeutic window.” This means the difference between the effective beneficial dose is not much different than a harmful dose. Take too little blood thinner and you are at risk for stroke. Take too much thinner and you could suffer a bleed. Effective use of these kinds of drugs, therefore, require a compliant, educated, and motivated patient.

      Considering non-compliance of blood-thinners in particular, the huge difference between dabigatran and warfarin is that the doctor knows when a patient is non-compliant with warfarin; it’s our job to know, to check, to confirm, to look after the patient. With the new blood thinners, the doctor cannot know; the patient has to check, confirm, and take care of themselves–by taking the medicine. This is the exciting difference.

      And to answer your last question: Yes. Most doctors would agree that for the patient on warfarin who refuses to check the level of blood thinness (INR), it would be safer on nothing. Remember, this is what happens with rat poison. Coumarin (a form of warfarin) is spread out in pellet form in the cabinets or along the floors. The rats keep eating the pellets, and their blood grows so thin they die later of internal bleeding. The rats overdose themselves on warfarin.

  3. Having had a mild stroke shortly after my first catheter ablation, this topic is of intense interest to me. Thanks for writing about it. I am on dabigatran now, and I am finding that I miss the reassurance that comes from a good INR result. But I don’t miss it enough to want to go back on the rat poison.

  4. Been on Pradaxa since May. Been religious about the dose, but I wonder about the reason. My Doc say that my cox score is below 1, but I have periodic episodes. Am trying light dose flecainide,(50 mg 2xdaily) pulled me off of Multaq, and am mostly symptom free. Have a few breath catchers periodically, but nothing consistent. Question is how long can a guy go with this regimen? Am 58, a semi- runner now, and confused.

  5. John,
    As usual I appreciate your insightful commentary . Thanks for continuing the discussion on your blog. Keep up the great work . I agree that an ongoing and careful analysis of this new frontier in anticoagulation is a must!
    Melissa Walton-Shirley

  6. Being from Canada, I’m surprised at the “novel” idea of personal health care management.

    We have long done away with the molly-coddling of hand holding when it comes to patient care. Education as to personal responsibilities towards ones’ health have long been touted both by our practitioners and medias. That does not imply a lack of culpability or transparency to the process, but a larger awareness of our actions and consequences. Whether it is an implied consciousness or due to universal healthcare, remains to be proven.

    However, as your (US) litigious system grapples with the new consequences of Pradaxa, I would anticipate more practitioners avoiding the prescription of this blood-thinner due to its’ “novel” approach of personal responsibility and the inevitable rebuking of the placement of that responsibility upon the patient by the patient. Insert wry joke about the Do Not Step ‘Step’ here.

    Regardless, that is exactly my concern about Pradaxa. As a valvular patient who has antiphospholipid syndrome, I worry that moving to a “your blood is thin for prevention for all ischemic events” drug, is a bit unnerving, pardon the pun. Whilst I gladly would do away with the angst about daily TIAs’, cardiac/pulmonary/hepatic/kidney etc emboli, how do I know that my blood is thin enough?

    I cannot find any information regarding blood assays, but it would stand to reason that a thrombin inhibitor would affect APTT, DTT or PT, would it not? And as we have yet to know the factors that contribute to the formation of emboli in APS patients, how can we use a static drug in the treatment of a variable disease?

      1. Thank you for your kind words, but honestly, from a clinical standpoint, Pradaxa raises more questions than it answers.

        As a result, clinicians will need to assess patients more acutely, not only the obvious factors (age, lifestyle, socio-economics) but now compliance AND the predisposition of their presenting issues.

        With the promise of Rivaroxaban and Apixaban, both being Factor Xa inhibitors, one step before Pradaxa in the blood coagulation pathway, it begs the question of how far do we drill down the prothrombinase complex in order to properly manage coagulation? Do clinicians need to perform a complete hemotological profile with TDNA, ACA and Protein S screening before prescribing the new anticoagulants?

        Balance these questions with the costs associated to achieve these results, for due diligence of course, and the management of Pradaxa loses its’ competitive edge over Warfarin.

        In an age of the disintegration of the “continuity of care” paradigm, who wants to carry the burden of this responsibility? The GP? Surely not! The specialist? Possibly. The pharmacist? Even more intriguingly, yes. Unfortunately, I would suspect liability insurance will be the determining factor.

        As a patient, there is no margin for error so, the devil that you know may be better than the devil you don’t know.

        1. R,

          I am not sure why we would have to perform complex heme tests. Isn’t the advantage of the non-warfarin blood-thinning drugs, their simplicity and consistency of effect?

          I agree with your assessment that we docs will have to use more judgement, not less, in prescribing non-warfarin blood-thinners.

          And I must say that in choosing a blood thinner, lately, I find myself frequently defaulting to “the devil that I know, rather than the one that I don’t.” Especially in cases where a procedure like cardioversion or ablation is impending.

          Thanks for the thought-provoking questions.

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