Case 1
Tracy Minichiello, MD. The first case we’ll discuss is a 75-year-old man with mild chronic kidney disease (CKD). His calculated creatinine clearance (CrCl) is about 52 mL/min, and he has a remote history of a gastrointestinal (GI) bleeding 3 years previously from a peptic ulcer. He presents with new onset nonvalvular atrial fibrillation (AF), and he’s already on aspirin for his stable coronary artery disease (CAD).
How do we think about anticoagulant selection in this patient? We have a number of new oral anticoagulants and we have warfarin. How do we decide between warfarin vs one of the direct-acting oral anticoagulants (DOACs)? If we choose a DOAC, which one would we select?
David Parra, PharmD. The first step for anticoagulation is to assess a patient’s thromboembolic risk utilizing the CHA2DS2-VASc and bleeding risk using a HAS-BLED score, or something similar. The next question is which oral anticoagulant to use. We have widespread experience with warfarin and can measure the anticoagulant effect easily. Warfarin has a long duration of action, so perhaps it’s more forgiving if you miss a dose. It also has an antidote. Lastly, organ dysfunction doesn’t preclude use of warfarin as you can still monitor the anticoagulant effect. So there still may be patients that may benefit significantly from warfarin vs a DOAC.
On the flip side, DOACs are easier to use and perform quite acceptably in comparison with warfarin in nonvalvular AF. There are some scenarios where a specific DOAC may be preferred over another, such as recent GI bleeding.
Dr. Minichiello. Do you consider renal function, bleeding history, or concomitant antiplatelet therapy?
Geoffrey Barnes, MD, MSc. A couple of factors are relevant. I think we should consider renal function for this gentleman. However, I look at some of the other features as Dr. Parra suggested. What’s the likelihood that this patient is going to take the medicine as prescribed? Is a twice-a-day regimen going to be something that’s particularly challenging? I also look at the real-world vs randomized trial experience.
This patient has a remote GI bleeding history. Some of the real-world data suggest there might be some more GI bleeding with rivaroxaban, but across the board, apixaban (in both the randomized trials and much of the real-world data) seem to have a favorable bleeding risk profile. For a patient who is open and reliable for taking medicine twice a day, apixaban might be a good option as long as we make sure that the dose is appropriate.
Arthur L. Allen, PharmD, CACP. In pivotal trial experience, dabigatran and rivaroxaban demonstrated an increased incidence of GI bleeding compared with warfarin. In some of the real-world studies, rivaroxaban mirrors warfarin with regard to bleeding, whereas dabigatran and apixaban have a lower incidence. In the pivotal trials, apixaban did not have a trigger of increased GI bleeding, but I would let the details of this patient’s GI bleeding history help me determine how important an issue this is at this point.
The other thing that is important to understand when considering choice of agents: As Dr. Parra mentioned, we do have quite a bit of experience with warfarin. But comparing the quality of evidence, the DOACs have been investigated in a far more rigorous fashion and in far more patients than warfarin ever was in its more than 60 years on the market. For example, the RE-LY trial alone enrolled more than 18,000 patients. Each of the DOACs have been studied in tens of thousands of patients for their approved indications. Further, we shouldn’t forget that the risk of intracranial hemorrhage is reduced by roughly 50% by choosing a DOAC over warfarin, which should be a consideration in this elderly gentleman.
Dr. Minichiello. In the veteran population, there is a sense of comfort with warfarin, and some concerns have been raised over a lack of reversibility for the newer agents. We have patients who have trepidation about starting one of the new anticoagulants. However, there is a marked reduction in the risk of the most devastating bleeding complication, namely intracranial hemorrhage, making the use of these agents most compelling. And when they did have bleeding complications, at least in the trials, their outcomes were no worse than they were with warfarin, where there is a reversal agent. In most cases the outcomes were actually better.
Dr. Barnes. You often have to remind patients that there was no reversal agent in these huge trials where the DOACs showed similar or safer bleeding risk profiles, especially for the most serious bleeding, such as intracranial hemorrhage. I find patients often are reassured by knowing that.