Dabigatran: a replacement for Coumadin and Lovenox?

The results of the RE-LY study were just published in the New England Journal of Medicine. Since this blog is for both doctors and patients, I will try to split the difference in medical info. The article discussed a brand new anti-coagulant, dabigatran, which will be marketed here in the U.S. under the trade name Pradaxa, and is a pill to be taken twice a day.

The drug blocks the action of thrombin, which takes part in the final step of the clotting cascade. Thrombin converts fibrinogen to insoluble fibrin, which then makes a blood clot solid and tenacious.

The greatest risk factor for forming a clot is relative stasis of the blood flow next to the wall of a blood vessel. This clotting possibility is enhanced by some (unknown ) chemicals secreted by some cancers, especially prostate, as well as prolonged immobility, such as flying across the Atlantic Ocean.

The initial oral anti-coagulant was Coumadin (actually Warfarin, which was developed as a rat-killer by the University of Wisconsin from a chemical component of hay) which prevents blood from clotting, and so the rat bleeds to death internally. When Coumadin is given to humans, weekly blood tests are needed: a PT, as well as a monthly Hct. There is a narrow therapeutic window for Coumadin: too much and the patient can develop a GI or an intracranial bleed, and too little and the patient's blood will clot where it is not supposed to. If the patient finds the bleeding risk psychologically intolerable, oral alternatives are aspirin, and aspirin + dipyrimadole (Aggrenox). Under many circumstances, injectable low molecular weight heparin (e.g. Lovenox) can be used; this requires no blood tests for monitoring, but the patient has to inject him/herself daily.

This particular study compared oral dabigatran to oral Coumadin in patients with non-valvular atrial fibrillation. In this condition, the left atrium quivers like the surface of a bowl of jelly rather than contracting rhythmically. The blood flow against the left atrium wall is relatively static, and clots can form in the left atrium which then break loose and can go up to the brain, causing a stroke. Coumadin has been shown to sharply reduce the risk of this event, and aspirin will also reduce the stroke risk, but less so. The study showed that the risk of stroke as well as the risk of bleeding was lower with dabigatran than with Coumadin, and the FDA has approved the use of this drug for patients with non-valvular atrial fibrillation.

I doubt that this study will ever be repeated, so let us assume (and hope) that the conclusion reached is a correct one. The question then becomes: will dabigatran be used for other medical problems where Coumadin or aspirin is indicated, without going through a formal study? This is called an off-label use, but is neither illegal nor immoral. For instance, once it was found serendipidously that calcium channel blockers (used for hypertension and angina control) also reduced the frequency of migraine headaches, it was frequently prescribed for this purpose.

So now we have an anticoagulant that causes less bleeding than Coumadin in therapeutic doses (I am unaware of any bleeding studies vis-a-vis aspirin), need no weekly blood tests, and can be taken orally. I can think offhand of many medical problems where this drug might be useful.
In no particular order they are:

1) Cross-Atlantic flying----no studies of aspirin have shown reduction in the incidence of deep vein leg thrombosis.

2) Heart valve replacement---instead of Coumadin.

3) Post-op, especially in orthopedic procedures such as total hip or knee replacement

4) Any deep vein thrombosis

5) Any pulmonary embolus

6) Pulmonary hypertension, baggy heart with EF less than 20%, migraine headaches

7) Post-MI to reduce the risk of a second MI, instead of aspirin

8) (Unknown as yet) Patients with the need for anti-coagulation who have relative contra-indications such as erosive esophagitis, gastric ulcers, or duodenal ulcers

9) ? Patients with the lupus anticoagulant

10) Patients with factor V or Leiden problems

11) Patients with polycythemia or polythrombocytosis

12) Patients with TIA or embolic stroke

13)? Patients with any cancer who develop a deep vein thrombosis

etc., etc., etc.

Please feel free to post any other suggestions.