Use of Anticoagulants to Prevent Stroke in Nonvalvular Atrial Fibrillation - Episode 8
Michael B. Bottorff, PharmD: With the DOACs (direct oral anticoagulants), you could look at some of their advantages as being a more rapid onset of effect. And if you do get a major bleeding complication because of their shorter half-life, the effect on that bleed will be (usually) shorter. Some of their disadvantages include that they do not require routine monitoring for their therapeutic effect. Many people consider this an advantage, but some would consider it a disadvantage if you wanted to do a procedure and you don’t really know how anticoagulated that patient is because you don’t have a readily available test for that.
The availability of the DOACs has changed our thought process as we see a new patient, let’s say, with atrial fibrillation (AFib). You now have several options, since there are 4 DOACs plus warfarin. So, you have to individualize that decision-making process for each individual patient, and in fact, incorporate the patient’s wishes, in many cases, into which of those agents you might select for therapy.
It was interesting when the Graham study came out, recently, to look at how that study was conducted, the kinds of patients that it represented, and what the results were. David J. Graham works for the FDA, so this was an FDA-generated study that looked at a Medicare population. Therefore, it does represent that common AFib patient—65 years or older. They looked at 119,000 patients who were on either Medicare Part A, Part B, or Part D. Therefore, they had medical claims as well as prescription claims data to assess the effects of drug therapy on outcomes.
It was nice to see that this trial was actually conducted by the FDA because, I think, what that represents, and if you’re familiar with how the FDA does drug surveillance (or postmarketing drug surveillance), is that they’ve typically (in the past) relied on spontaneous reports that just come in from prescribers or other healthcare providers. This is a different way for the FDA to look at postmarketing performance of a drug in the real-world environment, and it’s important that the FDA is the one who initiated this as part of their role in looking at postmarketing drug surveillance.
The Graham study looked at the outcome associated with the 2 usual doses—rivaroxaban 20 mg a day, and dabigatran 150 mg [twice daily], assessing the rates of thromboembolic stroke, the rates of intracranial hemorrhage, the rates of non-cranial major bleeds (including gastrointestinal [GI] bleeds), and then, total mortality. And in this observational study, what they found was that compared with dabigatran, rivaroxaban was associated with a nonsignificant reduction in the rates of thromboembolic stroke. But it also demonstrated significant increases in the rates of both intracranial hemorrhage and non-intracranial major bleeds, including an increased rate of GI bleeds. And there was a nonsignificant increase in mortality associated with rivaroxaban, as well.
The clinical importance of this study is that in the absence of proactive head-to-head clinical trials, we’re going to need to rely on observational studies like the FDA did to get an assessment of how these drugs compare with each other in the real-world environment. And through using the Medicare data, I think the study represents how these drugs are performing relative to each other in a real-world environment.
One of the advantages of DOACs is that they have a simplified dosing strategy relative to warfarin. There’s typically a usual dose like the doses we talked about in the Graham trial. The only major need for a dose reduction or alteration in that standard dose would be based on either renal function (because all the drugs have varying degrees of renal elimination as part of their elimination process), or other patient-specific factors (depending on which of the DOACs we’re talking about). Otherwise, a pretty standard dosing applies to the majority of patients.
For managing their side effects, almost always the only side effect you’re ever going to see is if these drugs cause a bleed. So, the side effect management is typically just related to whatever bleeding complication may occur, whether that’s a minor bleed or a major bleed.