Roundtable Discussion: Anticoagulation Management
I’d like to take a moment and step back to the case in the context of the GI bleeding. When we look at patients with a history of GI bleeding, it is important to understand the circumstances that surround it. This individual had a GI bleed 3 years previously and peptic ulcer disease. In these situations I ask whether the patient was taking over-the-counter nonsteroidal anti-inflamitory drugs at the time, had excessive alcohol use, or was successfully treated for Helicobacter pylori. All of these may influence whether or not I think the GI bleed is significant to influence the DOAC choice.
The other thing I consider is that the overall risk of major GI bleeding in those pivotal DOAC trials was quite small, < 1.5% per year with dabigatran 150 mg twice daily and < 1% per year with apixaban. The numbers needed to harm were quite high, over 200 patients per year with dabigatran 150 mg twice daily vs warfarin and over 350 patients per year with edoxaban 60 mg daily vs warfarin. There are no head-to-head comparisons with DOACs, but this small increased risk vs warfarin may still be an important consideration in some patients. In addition, it is important to remember that intracranial hemorrhage and fatal bleeding was less in all the pivotal NVAF trials with the DOACs when compared with warfarin. So that is something we need to reinforce with patients when we discuss treatment regardless of the DOAC selected.
Case 2
Dr. Minichiello. The next case is a 63-year-old man with hypertension, diabetes mellitus, nonvalvular AF, and he is taking dabigatran for stroke prevention. He presents in the emergency department with chest pain, and he is found to have a non-ST elevation MI. He goes to the cath lab and he is found to have a lesion in his left circumflex. The patient receives a newer generation drug-eluting stent. What are we going to do with his anticoagulation? We know he’s going to get some antiplatelet therapy, but what are our thoughts on this?
Dr. Parra. This is something that we run into all too often. I think the estimates are about 20% to 30% of patients who have indications for anticoagulation also end up having ischemic heart disease that requires PCI. The second thing is that we know combining an anticoagulant with antiplatelet therapy is associated with a 4% to 16% risk of fatal and nonfatal bleeding, and we have found out in patients with ischemic heart disease that when they bleed, they also have a higher mortality rate.
We’re trying to find the optimal balance between ischemic and thrombotic risk and bleeding risk. This is where some of the risk assessment tools that we have come into play. First, we need to establish the thrombotic risk by considering the CHA2DS2-VASc score, and the factors associated with increasing bleeding risk and stent thrombosis. You have time to work this out because, initially, all patients that are at sufficiently high thrombotic risk will receive dual antiplatelet therapy and anticoagulation therapy for a given period. This gives providers time to use some of those resources and figure out a long-term plan for the patient.
Dr. Allen. The fear and loathing that this brings up comes back to some historic things that should be considered. What we did for drug-eluting stents or bare-metal stents comes from older data where different stent technology was used. The stents used today are safer with a lower risk of in-stent thrombosis. Historically, we knew what to do for ACS and PCI and we knew what to do for AF, but we didn’t know what to do when the 2 crossed paths. We would put patients on warfarin and say, “Well, for now, target the INR between 2 and 2.5 and good luck with that.” That was all we had. The good news is now we have some evidence to move away from the use of dual antiplatelet plus anticoagulant therapies.
There were 2 DOAC studies recently published: The PIONEER-AF trial used rivaroxaban and more recently the RE-DUAL PCI trial used dabigatran. Each of the studies had some issues, but they were both studied in AF populations and aimed to address this issue of triple therapy. The PIONEER-AF trial looked at a number of different scenarios on different doses of rivaroxaban with either single or dual antiplatelet therapy compared to triple therapy with warfarin. The RE-DUAL PCI trial with dabigatran was less complex. Both studies were powered to look at safety, and they did show that with single antiplatelet plus oral anticoagulation regimens, the incidence of major bleeding complications was reduced.
However, that brings up some issues about how the studies were conducted. Both studied AF populations and in some cases did not study doses approved for AF. Yet at the same time, the studies were not powered to look at stroke outcomes, which raises the question: Are we running the risk of giving up stroke efficacy for reduced bleeding? I don’t think that we’ve fully answered that, certainly not with the PIONEER AF trial.
