VOYAGER PAD: Clinical Rationale and Study Design

Transcript: Deepak L. Bhatt, MD, MPH: Mike, Marc, and Matt, we’ve had a great discussion here, with all of us philosophizing and chatting at home. But while we’ve just been chatting and fraternizing, Manesh Patel has actually been working for a living. He’s been hard at work, called into action at the Duke University catheterization laboratory in the middle of this COVID-19 [coronavirus disease 2019] emergency. Welcome, Manesh. How are you doing, first of all?

Manesh R. Patel, MD: I’m doing well. Thanks for having me, everyone. It’s good to see you all.

Deepak L. Bhatt, MD, MPH: How are things with respect to COVID-19? We all had a brief discussion about that. How are things in your neck of the woods in North Carolina, specifically Duke University?

Manesh R. Patel, MD: We’re still a little fortunate. There are places like New York, Louisiana, and others that are pretty ravaged right now. We do have cases. We have about 2000 cases in the state and 200 cases in the hospital, and we anticipate our peak in a few weeks. But what’s most telling, as I’m sure you all discussed, is the tremendous sense of camaraderie and people working together to try to help beat a common enemy. Obviously, we’re all working hard to do that.

Deepak L. Bhatt, MD, MPH: That’s terrific. It’s so great that you could join us. I’m glad you were there to provide that emergency coverage in the catheterization laboratory. Your timing is always as perfect. We’ve basically been talking about everything other than the latest data, and we were just about to launch into a discussion on VOYAGER PAD. Of course, Marc Bonaca presented that at the ACC [American College of Cardiology] meeting as a late breaker. The data were just published in the New England Journal of Medicine, so congratulations to you both on that. Manesh, perhaps you could start with why VOYAGER PAD was done. What was the design? Who were the exact patients? Why couldn’t we have just stuck with aspirin and clopidogrel? That’s what I was doing in my practice. Why did VOYAGER-PAD need to be done?

Manesh R. Patel, MD: Thanks, Deepak. The reason VOYAGER PAD was done is that similar to a lot of methods. We’ve been doing something in clinical practice and extrapolating without evidence for doing it. We were taking care of patients undergoing peripheral revascularization using the best available data extrapolated from coronary care. As you said, I too was using aspirin and clopidogrel, sometimes using aspirin alone.

I’m sure the surgeons were sometimes using aspirin or warfarin. There weren’t a great amount of data. After COMPASS and ATLAS ACS 2-TIMI 51, thinking about a fair bit of prior evidence that 2.5 mg of rivaroxaban plus aspirin might help patients chronically with coronary and vascular disease, the question was, “Does that help somebody acutely after a peripheral revascularization procedure?” Specifically, since there weren’t a tremendous amount of data in that space, we wanted to look at patients who have just undergone that procedure and look at a composite of events that Marc Bonaca and others have discussed with you regarding acute limb ischemia, vascular amputation, MI [myocardial infarction], stroke, and cardiovascular death as a 5-part composite.

We endeavored to take around 6500 patients and evaluate those undergoing either endovascular revascularization or surgical lower-extremity revascularization. We randomized them to the addition of rivaroxaban at 2.5 mg twice a day with aspirin compared with aspirin and placebo and looked for those events, and we were able to identify a broad group of people. All you had to do to get into the trial was have a revascularization event and have a plan to be on aspirin afterward, and you could be randomized into the study. A lot of people ask about clopidogrel. You could get clopidogrel. We allowed those people who were planning on using clopidogrel to use it out to 6 months, but they used it only around 30 days or so. Most of the patients were done by day 90, and we followed them for the events I described.

Deepak L. Bhatt, MD, MPH: That’s really a clever, practical design, and it respected the fact that there are a number of folks who did believe that aspirin or clopidogrel was the standard of care, even though there wasn’t great evidence to support that, other than extrapolating from the coronary literature.

Transcript Edited for Clarity