Pradaxa: More Concerns. More Myocardial Infarctions?

Pradaxa is part of a new group of anticoagulants (thrombin X inhibitors) that eventually will allow anticoagulation by the pill route without requiring patients to alter their food and medication intake and avoid foods and medications that interfere with the anticoagulant as patients must do with Warfarin. Pradaxa additionally eliminates the need to take blood tests (INR/ PT) to monitor the dosage as one has to do with Warfarin (Coumadin).

There is a large commercial advertising campaign underway on TV and print media to encourage patients with atrial fibrillation to ask their doctors to switch them from Coumadin to Pradaxa (Dabigatrin).  The campaign bases its claims on the RE-LY trial of 18,000 patients at 80 medical centers throughout the world who took the 150 mg dosage and had significantly fewer strokes than patients taking Warfarin.  The original study was criticized because many of the patients in the Warfarin (Coumadin) group were not on enough Warfarin or at a therapeutic PT/INR to prevent embolic strokes so the comparison with Pradaxa may not be valid. Another criticism involved the fact that Pradaxa can cause major bleeding and there is no antidote to stop the bleeding. Patients on Pradaxa who are bleeding are advised to undergo hemodialysis to remove the drug from their system because there are no medications or treatments available to stop Pradaxa related bleeding.

One wonders how the Food and Drug Administration approved this product for general use under these circumstances without conducting further testing?  The issue becomes even more confusing with the addition of data presented by Ken Uchino, MD, and Adrian Hernandez MD, PhD of the Cleveland Clinic in the online version of the Archives of Internal Medicine. They claim that by reviewing the RE-LY data there is a 38% relative increase in the risk of a myocardial infarction (MI) or heart attack in the Pradaxa group. In an accompanying editorial in the same journal, clinicians at the Hadassah- Hebrew University Medical Center in Jerusalem wrote, “The robust finding that Dabigatran is associated with increased rates of MI (heart attack) is alarming and emphasizes the need for continued critical appraisal of new drugs after phase III trials.”

In my practice I generally will not switch to a new or controversial medication until it has been on the US market for at least one year. I make exceptions for orphan drugs, products to treat incurable diseases with no other choices available. The 12 months gives the medical and scientific community a chance to see how the medication performs and what unexpected adverse effects may be associated with it.

Thrombin X inhibitors are the wave of the future. With no way to stop the bleeding, and data on their safety and efficacy still accumulating, they are just not ready for prime time yet.