I have blogged about atrial fibrillation and the need for anticoagulation in the past. Some blogs have gone over the history of Coumadin, and more recently, the development and approval of Pradaxa. Also, there have been blogs about some of the more novel issues' with Pradaxa.
Perhaps the most novel element about Pradaxa is the fact that you can not reverse the effect of the drug. If you have a bleeding issue on the drug, you have to allow it to wear off and support the problem. Pradaxa, unlike warfarin or heparin, cannot be reversed.
Pradaxa is only one alternative to warfarin that is now being developed. One other new drug, rivaroxaban, is going to be available soon.
Pradaxa is a direct thrombin inhibitor, and rivaroxaban is an oral direct factor Xa inhibitor. Trust me, you don’t want to know anymore. It will make your head explode. The only reason I bring it up is so you understand that the clotting pathway of our bodies is being interacted in different places by these two drugs and so presents two different opportunities.
On September 8, 2011, the FDA advisory committee voted to approve the drug for the use in atrial fibrillation to prevent stroke. A large study demonstrated it to be non inferior to warfarin when given once a day. This drug is an oral compound which does the same thing as Lovenox, a drug most people who have been hospitalized recently are aware of. Lovenox is the drug they inject in your abdomen to prevent blood clots from forming in your legs.
This drug will be known as Xarelto. Don’t ask; I certainly don’t know how they came up with that. The interesting thing about this drug, and the purpose of this blog is this: this drug, which is not yet approved here in the United States, appears to have a reversal agent.
Published in Circulation on September 6, 2011 (Circ2011;DOI: 10.1161/circulationaha.111.029017), this article reports on the use of PCC, or prothrombin complex concentrate, in volunteers who are test subjects. They do not have the illness that is being treated.
This study compared rivaroxaban and dabigatran. When given both drugs, it prolongs the PT or prothrombin time. We can test to see whether someone is taking Pradaxa with the PT, but the intensity of the effect is not measured unlike warfarin and the INR. When PCC was given to the volunteers, the rivaroxaban was reversed but not the Pradaxa. So PCC may be a useful drug to immediately reverse the effect of the drug in the case of a bleeding emergency or if emergency surgery is needed.
This is a small study, and more work will need to be done before this is accepted, but it is provocative and useful information. It may well be a great selling point between these two drugs in addition to Xarelto being used once a day.
Progress. Slow, not always steady, but always toward better patient care.