Warfarin: The Devil You Know

The next issue of The Medical Letter will include an article on Oral Anticoagulants for Atrial Fibrillation. For decades, the only oral anticoagulants were vitamin K antagonists such as warfarin (Coumadin, and others), but recently 3 new drugs have emerged as competitors: dabigatran (Pradaxa), which is a direct thrombin inhibitor; rivaroxaban (Xarelto), a direct factor Xa inhibitor; and apixaban (Eliquis), another factor Xa inhibitor, but one that has not yet been approved for use in the US. We discussed these agents briefly in our 2011 Treatment Guidelines issue on Antithrombotic Drugs (Volume 9, p. 61, October 2011). In patients at risk for thromboembolism, such as those with atrial fibrillation, all of these drugs have a narrow therapeutic index: not enough anticoagulation could permit an ischemic stroke, but too much could lead to a hemorrhagic stroke.

So why, in walking such a fine line, would you ever prescribe a new drug with inevitable unknowns over an old one that we have used forever and know well? Warfarin, I was once told by someone in a position to know, causes more problems than all the other drugs in the pharmacopoeia put together. Well, that has to be an exaggeration, but it is a pain to use. Patients need to have their level of anticoagulation (INR) monitored frequently (and the dose of the drug changed, if necessary). They need to be careful about their intake of green, leafy vegetables, which contain substantial amounts of vitamin K that can interfere with the anticoagulant effect. And someone (the patient, the prescriber, or the pharmacist) has to pay attention to the other drugs the patient is taking, because many other medications can interact with warfarin to increase or diminish its anticoagulant effect.

The newer drugs do not need monitoring and frequent dosing changes.  That is a clear advantage over warfarin. But if they cause serious bleeding, as all anticoagulants sometimes do, there is no direct antidote; warfarin-associated bleeding can be reversed by administration of vitamin K. So are the new anticoagulants less safe than warfarin? And how do they compare in effectiveness? Watch for some answers in the next issue of The Medical Letter.

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