Real-World Applications of Trial Data in PAD

Transcript: Deepak L. Bhatt, MD, MPH: Manesh, what should we do with peripheral interventionalists? Maybe this is applied to what we do as coronary interventionalists. What do you think is the preferred regimen? Let’s say we stent an SFA [superficial femoral artery] now. Should they go out on aspirin or clopidogrel and this vascular dose of rivaroxaban? Or should it just be an aspirin and this low-dose rivaroxaban? What is the optimal cocktail: for how long and with which agents?

Manesh R. Patel, MD: This is something a lot of people have asked and continue to ask. For the first time, we have an evidence-based answer. VOYAGER PAD would strongly suggest that at least the core of that therapy should be rivaroxaban, at what Mike has called a “baby dosage” or 2.5 mg twice daily dosage with aspirin. Whether you add clopidogrel is going to be dependent on your belief. There’s less evidence here, but some would say, “Manesh, clopidogrel was used in some of the stent trials, and I want to use some of it.” I’m not suggesting all the endovascular doctors should give up clopidogrel. If it was a straightforward SFA without a bunch of complexity and without a drug-coated product, where some of that clopidogrel was tested, I would likely say you can go home safely, based on what we’ve seen with VOYAGER PAD, and have an efficacy reduction after 3 years with low-dose rivaroxaban and aspirin.

If you were going to use short-term clopidogrel, remember it wasn’t randomized but it was stratified, that you were going to use it. I’m defining short-term clopidogrel as fewer than 6 months, 90 days. The average in the trial was 30 days. It didn’t modify the effect that we were seeing. In fact, we saw a little more bleeding. That message is not going to be different from what we’ve seen in other messages, which is when you get to triplet therapy, even with the baby dose of rivaroxaban, bleeding goes up. People probably stop the therapy. You’re going to have to have a really specific efficacy need when I’m thinking about that.

Deepak L. Bhatt, MD, MPH: That’s really good advice. What about an infrapopliteal drug-eluting stent that’s placed? What would you do there?

Manesh R. Patel, MD: That’s a tougher case because with an infrapopliteal drug-eluting stent in itself, we’ve already gone 2 levels beyond where we might have substantial evidence. We’re sunbathing on the evidence prebeach, which I do a lot of. I would just say that there, I would potentially still use rivaroxaban and aspirin. You might use the short course of DAPT [dual antiplatelet therapy] or at least add clopidogrel because you’re saying, “Look, I think it’s a coronary-size vessel. I believe in that thrombotic risk.”

We’ll have more data as we look at the angiographic subsets. I would still say rivaroxaban by itself in those patients who are not within the anatomic subset. Marc has probably highlighted—and I know Matt will think about this too—that a third of the patients in the VOYAGER PAD trial had critical limb ischemia, and if anything, they look even better than the patients with claudication. Those are what I’ll call our highest-risk patients, and I’m sure some of them are getting the types of interventions we’re talking about, whether it’s surgical or endovascular. Rivaroxaban certainly seems better there.

In the peripheral space, I’m moving away from that clopidogrel postrevascularization based on these data. We’ll know more about specific anatomic subsets from a really well-done collection of the angiograms in about 3000 of these patients. We still have to go review them and do a bunch of work, but that will be informative.

Deepak L. Bhatt, MD, MPH: Those are really important points. There is more to come as is the case with all these large well-done trials. Yes, there’s the primary analysis or 2, but then there’s a bunch of other analyses that can sometimes be even more informative. Before we leave VOYAGER PAD, do you have any final comments, Marc? It was your baby, after all. Any parting thoughts on it?

Marc P. Bonaca, MD, MPH: I was fortunate enough to get to present it. As with every trial, it’s a community that runs it and a lot of partnership of many folks. Manesh’s leadership was great. I think what was said is true about DAPT. It wasn’t a randomized trial, but this does distinguish from the coronary space where there are actually good data for clopidogrel. Although we can’t say whether clopidogrel helped at all, we know it did add more bleeding. To me it brings back the question of, “Why use clopidogrel at all in this space? Were we just doing it because we had nothing else?” Two drugs is generally enough, and we’re learning in almost every other setting that 2 is better than 3 when it comes to antithrombotics. I hope we learn more, and I wouldn’t be surprised to see a trend where people are abandoning clopidogrel more and just reserving it for really high-risk interventions. But as you said, there’s more to come, and it was a privilege to be part of the study.

Deepak L. Bhatt, MD, MPH: Congratulations to all of you on VOYAGER PAD for a really a tremendous effort. As you said, it takes large international teams to make these clinical trials happen.

Transcript Edited for Clarity