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“It’s really sad—but it’s true: In the PAD [peripheral arterial disease] space, we’re really behind. We’re behind in our understanding of the physiology, the anatomy to some extent, the way the disease permeates through the leg.”
Those are the words of Anahita Dua, MBChB, an assistant professor of surgery at Massachusetts General Hospital in Boston, as she discusses the fight against amputation in PAD patients who have been revascularized. She is speaking alongside Kush Desai, MD, associate professor of radiology at Northwestern University Feinberg School of Medicine in Chicago, and Christian T. Ruff, MD, director of general cardiology at Brigham and Women’s Hospital in Boston, as the trio of vascular specialists consider the use of direct oral anticoagulants (DOACs) for the treatment of PAD post-revascularization, and novel data that can be used to mitigate the risk of thrombosis, in a new multi-part CME activity entitled, “Beyond the Procedure: Evolving the Current Standard of Care for Patients with PAD.”
Calling upon emerging data on DOAC use among PAD patients, the panel of experts survey the current PAD guidelines and the pivotal COMPASS trial, the latter of which looked at the benefit of low-dose rivaroxaban plus aspirin as compared with aspirin alone in those patients with chronic vascular disease.
In part one, “Digging Deeper Into DOACs for PAD,” Ruff delves into guidelines from both the vascular and cardiology worlds as he introduces the subject matter. For patients with symptomatic PAD, he says, if a patient has recently also had a coronary stent placed or acute coronary syndrome, they will likely benefit from dual antiplatelet therapy (DAPT). More broadly, Ruff adds, this is where a strategy of aspirin and clopidogrel, or aspirin plus rivaroxaban, can be considered.
“There is some equipoise here with either DAPT or low-dose rivaroxaban plus aspirin to reduce adverse cardiovascular events,” he explains. “It is important to remind the audience there are no clinical trial data comparing DAPT as a strategy to the low-dose rivaroxaban and aspirin strategy.”
Ruff points out more intensive strategies are favored in patients with high ischemic risk and those with “overt” atherosclerotic disease or diabetes, for example. “Anytime you’re using combination antithrombotic therapy, patient selection is critical because obviously we want to reduce ischemic and thrombotic events—but it will always come at the cost of an excess in bleeding,” he says.
Who gets rivaroxaban?
Dua asks her fellow panelists more specifically how specialists determine which patients receive a strategy that includes rivaroxaban. Ruff summarizes his thought process by asking, “Is this a patient who is at high risk in the acute period, do they have disease in multiple beds?
“And, if they do,” he says, “I’m going to be more intensive—particularly, the dual pathway strategy is good for preventing MACE [major adverse cardiac events] in general, but also limb events— and use it in my patient. But I’m definitely much more thoughtful in the chronic setting, or in patients who maybe just have single-bed disease, maybe just PAD.”
In part two of the CME activity, Dua points out the only level 1A evidence specialists have to call upon in the guidelines to support the way in which they treat PAD patients post-revascularization is to give them “monotherapy with aspirin, whether that be in an endovascular situation” or in a surgical setting. Yet, treatment strategies carried out are “all over the board,” she says, which “is problematic because it is not data-driven.” Dua highlights the importance of recognizing that in the endovascular space specialists have used DAPT, typically with aspirin and clopidogrel, which amounts to “weak” level 2C evidence, she says.
DOACs after revascularization
Dua then introduces the VOYAGER PAD trial, which looked at more than 6,500 PAD patients who had undergone successful revascularization and who, within the 10 days afterwards, were randomized to a regimen of either rivaroxaban plus aspirin, or a placebo plus aspirin. Pointing to the trial’s primary efficacy outcome, Dua says the most important takeaway “is that, if you’re giving patients rivaroxaban plus aspirin versus aspirin alone, patients have less of a need to treat, less of a need to reintervene, and there is an absolute risk reduction in the primary outcomes.”
The trial was successful in demonstrating this among the patient cohort. VOYAGER’s main point was to make sure that giving rivaroxaban plus aspirin would result in a reduction in thrombotic and ischemic events “and simultaneously not increase the bleeding profile,” she adds, leading the Food and Drug Administration (FDA) to expand the approval for rivaroxaban plus aspirin to include patients who received lower-extremity revascularization for symptomatic PAD.
The panel goes on to ponder the implications of the VOYAGER trial data for practice. “One thing that this underscores is how difficult this is, and the investigators are to be applauded,” says Desai. The data are particularly important for those patients who have had to undergo a revascularization. Among other patients, such as those being managed for lifestyle modification, “we probably err on the side of being more conservative than with an intense therapy, unless they have significant polyvascular disease.”
Ruff says the question is a good one: “What’s an optimal strategy, DAPT or aspirin plus low-dose rivaroxaban? I don’t think we know the answer to that question,” he says. “So, if I have a patient that requires DAPT, say for their coronary disease, that might be what I choose for that patient. If the patient doesn’t require DAPT, and they need a more intensive regimen, and they’ve just had peripheral revascularization, then this might be an appealing strategy, particularly if their bleeding risk is reasonable.”
Part three of the CME activity hones in on three sample PAD patients who are potential candidates for a rivaroxaban plus aspirin treatment strategy. Ruff, Desai and Dua introduce the cases and discuss application of data previously outlined during the activity. They include one patient who presents with polyvascular disease and symptomatic PAD; another who has undergone endovascular revascularization for lower-extremity PAD, has a 50-year smoking history and is a diabetic; and a third with non-healing wounds, chronic limb-threatening ischemia and coronary artery disease who was already on warfarin for a history of atrial fibrillation.
In discussion, Dua points toward the “new frontier” posed by increasing issues specialists are seeing in the microvasculature. Patients are living longer, are more complex, and they have more chronic kidney disease, she says.
By 2045, Dua adds, “we’re talking about thousands of patients who are going to be affected.”
In all three case studies, concludes Desai, “you can make a case that a dual-pathway approach makes sense in all those patients, whereas before we were a little bit in the hinterlands trying to figure out what’s the right thing to do.”
Visit https://www.achlcme.org/pad-patient-care-svs and learn about mitigating thrombosis risks to stop amputation post-PAD revascularization. Supported by an educational grant from Janssen Scientific Affairs, LLC.