Friday, September 24, 2010

From to ximelagatran to dabigatran - how far have we come?

I still remember the days when people thought ximelagatran was going to change the world of anticoagulation. The days of the Coumadin (warfarin) clinics seemed numbered. People who would require frequent INR checks would no longer have to get poked with needles. They could eat all the green vegetables they desire. They would no longer take rat poison. Then, the sad news about ximelagatran hit the news. Ximelagatran (proposed trade name Exanta) was not going to be approved by the FDA because of liver toxicity. That was 2006.

Fast forward now to 2010 and we see that the FDA advisory committee (not the FDA, but the FDA advisory committee) unanimously today recommended the approval of dabigatran. This means that the FDA will probably approve dabigatran in the near future, but we still need to wait and see. Meanwhile, a host of other new anticoagulant drugs are waiting in line.

So what are these new oral anticoagulants? Let's see what Wikipedia has to say:
  • Direct thrombin inhibitors (DTIs) are a class of medication that act as anticoagulants (delaying blood clotting) by directly inhibiting the enzyme thrombin. Agents in the pipeline include: dabigatran, melagatran (and its prodrug ximelagatran), and others.
  • Direct factor Xa inhibitors ('xabans') are a class of antithrombotics which act directly upon Factor X in the coagulation cascade, without using antithrombin as a mediator. Agents in the pipeline include: rivaroxaban, apixaban, edoxaban, otamixaban, and others.
The landscape of oral anticoagulation is about to change if these new oral agents get approved by the FDA. What role will Coumadin (warfarin) play in all of this? Will we look back in 20 years and wonder how we managed patients on a drug like Coumadin? Will these new anticoagulants stand the test of time? What will happen to all the injectable agents like enoxaparin (Lovenox), certoparin (Sandoparin), tinzaparin (Innohep), dalteparin (Fragmin), and others?

Physicians will need to be more familiar with the pharmacological profiles (half-life, interactions, etc.) as they choose among the myriad of available agents when they're treating patients with atrial fibrillation, DVT, or PE. Hospitalized patients at risk for DVT may no longer need to suffer from multiple injections if they simply need to take a pill. These emerging agents may also be used for patients who have artificial heart valves, those who have other types of hypercoagulable disorders, and more.

Back in 2006, we thought we were going to see a revolution in anticoagulation management, but it didn't happen. Now, in 2010, it appears like we may truly be looking at a new era.

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