Dr. Parra. I agree. When we look at those trials, 2 things come to mind. First, the doses of dabigatran used in the RE-DUAL PCI trial were doses that have been shown to be beneficial in the nonvalvular AF population. Second, a take-home point from those trials is the P2Y12 inhibitor that was utilized—close to 90% or more used clopidogrel in the PIONEER-AF trial. Clopidogrel remains the P2Y12 inhibitor of choice. One of the other findings is that the aspirin dosing should be low, < 100 mg daily, and that we need to consider routine use of proton pump inhibitors to protect against the bleeding that can be found with the antiplatelet agents.
Also of interest, the European Society of Cardiology (ESC) recently released a focused update with some excellent recommendations on dual antiplatelet therapy in coronary artery disease in which they incorporated the results from the PIONEER-AF-PCI trial. The RE-DUAL PCI trial had not been published when these came out. If you’re concerned about ischemic risk prevailing, ESC recommendations based upon risk stratification are triple therapy with aspirin, clopidogrel, and an oral anticoagulant for longer than 1 month and up to 6 months and then dual therapy with 1 antiplatelet agent and an oral anticoagulant to complete the 12 months; afterward just oral anticoagulation alone. If the concerns about bleeding prevail, then we have 2 different pathways: one limiting triple therapy to 1 month and then dual therapy with 1 antiplatelet agent and an oral anticoagulant to complete the 12 months. But the ESC also has a second recommendation for patients at high risk of bleeding, which is dual therapy with clopidogrel and an oral anticoagulant at the offset for up to 12 months. I found these guidelines to be particularly helpful in terms of how to put this into practice.
Dr. Allen. There’s still so much concern about in-stent thrombosis. Although a smaller trial, we knew from the WOEST trial that single antiplatelet therapy with warfarin was reasonable. We know from the PIONEER-AF and RE-DUAL PCI trials that we didn’t get significantly more in-stent thrombosis by giving up the second antiplatelet. Whether or not we answered the stroke question is another issue, but the cardiology societies are still hanging on to dual antiplatelet therapy. I question if that’s based on the older data and the older stent technologies.
Dr. Minichiello. This highlights again that often we have to consider these patients’ case-by-case analysis, and that these decisions require multidisciplinary input. It involves coming together and figuring out in this particular patient, which of those 3 options would be best. We have a lot more options than we did just a short year or year and a half ago with at least some data providing comfort that DOACs at effective doses for stroke prevention in nonvalvular AF look like they can be combined with single antiplatelet therapy for post-PCI patients.
Dr. Barnes. Speaking as a cardiologist, this is a question I encounter all the time. I think everything said here is really well taken. I’ll just summarize to say for patients who have acute coronary syndromes and AF. First, I’m okay with using warfarin and now I’m okay using the DOACs, but the anticoagulant needs to continue for stroke prevention. Second, the patient has to be on clopidogrel as a P2Y12 inhibitor because it has the lowest bleeding risk profile. Third, the patient doesn’t always need 1 year of dual antiplatelet therapy the way we used to think of it. With newer generation stents and ongoing anticoagulation, you can get away with shorter courses of your antiplatelets, albeit 3 or 6 months. Providers should have a conversation with patients and think hard about how to balance clotting vs that bleeding profile.
Case 3
Dr. Minichiello. This case involves a 66-year-old man who has nonvalvular AF and is on warfarin. He has CKD, and his CrCl is about 30. He has hypertension, diabetes mellitus, and he is going to go for a colonoscopy. The proceduralist lets you know about the date and wants to know whether he needs to be bridged. He also has a remote history of a transient ischemic attack.
Dr. Allen. Historically, we’ve had detailed guidance on how to risk assess patients with AF, venous thromboembolism (VT), and mechanical heart valves in the periprocedural period. From that risk assessment the guidance helped us determine whether or not we should offer periprocedural bridging with heparin or low-molecularweight heparin.
The issue is that the detailed guidance was always based on expert opinion not hard science and there was no great evidence that we were preventing thrombotic events or that there was a net clinical benefit to bridging. Some retrospective cohort studies started coming out around 2012 that demonstrated an increased incidence of major bleeding events associated with bridging with no reduction in thrombotic complications. Some might argue that this is because thrombotic complications are so rare that you would have to have tens of thousands of patients for adequate power. Nonetheless, these studies were adequately powered to show a significant increase in major bleeding.
The best prospective trial data we have for this population comes from the BRIDGE trial, which randomized AF patients to receive dalteparin bridge therapy vs placebo during periprocedural interruptions in warfarin therapy. It too demonstrated a significant increase in the risk of bleeding complications associated with bridging with no significant reduction in the risk of thromboembolic events. Critics point out that some of the higher risk patients were underrepresented, and the same could be said about some of the other retrospective studies in the VT and mechanical valve populations.
We have waited for quite a while for guidances to catch up with these data. The most recent guidance published would apply to this patient. It was guidance for the AF population published by the American College of Cardiology (ACC) in early 2017. This guidance still encourages bridging in some of the moderate-to-high-risk AF patients.
To make a decision to bridge, you not only have to make an assumption that your patient is at such extraordinary thrombotic risk that you would find some reduction in thrombotic events associated with bridging, but also that the benefit is going to be so great that it would overcome this very clear increased risk of bleeding, resulting in a net clinical benefit. Only then would it make sense to bridge. Based on the available data, it is quite possible that no such patient population exists.