ANTIDOTE FOR WARFARIN TRIAL

As noted above, all three drugs caused fewer intra-cranial hemorrhages than warfarin. Two of the drugs (Pradaxa and Eliquis) were superior to warfarin in preventing strokes and other important blood clots, and Xarelto was very similar to warfarin. Despite the lack of availability of reversal agents for the new drugs, and the fact that they were being compared with warfarin, a drug that did have a reversal agent, they caused no more bleeding than warfarin, and one drug caused less (Eliquis).

ANTIDOTE FOR WARFARIN TRIAL

The approval of each of these drugs was based on a large clinical trial where the rates of strokes and bleeding were carefully monitored and compared. We have been asked if FDA should approve anticoagulant drugs that do not have a reversal agent. Pradaxa, Xarelto, and Eliquis, in contrast, have no antidote. If significant bleeding occurs in a patient taking warfarin, there is a reversal agent -vitamin K.

And whereas the effects of these drugs wane within a short time frame after they are stopped, a day or so, the effects of warfarin persist for many days after it is discontinued. In addition to being at least as effective overall as warfarin and less likely to cause hemorrhagic strokes, Pradaxa, Xarelto, and Eliquis have some advantages, including fewer interactions with food and other drugs, rapid onset, and freedom from the need to have periodic blood test monitoring. Of particular interest, the three new drugs were substantially less likely than warfarin to cause a particular kind of bleeding leading to stroke – a “hemorrhagic stroke,” a stroke caused by bleeding into the brain, which is different from the strokes caused by the clots that go to the brain in atrial fibrillation. On the basis of clinical trials that included more than 50,000 patients from around the globe, FDA concluded that all three drugs were either equivalent to, or more effective than, warfarin in preventing strokes, with an acceptable risk of bleeding. Like warfarin, all three are ‘blood thinners’ that reduce the overall risk of stroke related to atrial fibrillation but they also cause bleeding. In the last few years, FDA has approved three new oral anticoagulant drugs – Pradaxa (dabigatran), Xarelto (rivaroxaban), and Eliquis (apixaban). Thus, the dosage of warfarin must be carefully adjusted to keep the blood thinning effect in the right range. If the effect is too small, it will fail to prevent strokes if the effect is too high, it will cause excess bleeding. But the anticoagulant effect of warfarin must be carefully monitored with periodic blood tests. Until recently, warfarin (approved in 1954 and marketed under the brand names Coumadin and Jantoven) had been the only drug approved for the prevention of stroke in patients with atrial fibrillation. This is accomplished with taking anticoagulant drugs or ‘blood thinners.’ Decreasing stroke riskĪnticoagulants have been known for many years to produce a striking (more than 50%) decrease in the rate of stroke, but they also prevent clotting in locations and situations where clotting is desirable. There are a number of treatments - drugs and procedures - intended to correct the fundamental heart rhythm problem in patients with atrial fibrillation, but the main focus of treatment is to try to decrease the rate of stroke by preventing the formation of these blood clots.

The main concern, however, is that atrial fibrillation can lead to the formation of blood clots in the heart, which can travel to the brain and cause a stroke. Atrial fibrillation can produce palpitations, shortness of breath, lightheadedness, weakness, and chest pain, or may occur without symptoms. More than 3 million Americans have atrial fibrillation, a problem with the electrical system of the heart that causes an irregular heart rhythm.

Antidote for warfarin