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Optimizing Anticoagulation in Vascular Disease Patients: Reimagining the Standard of Care - Episode 8

The VOYAGER PAD Trial

The panel shares how data from the VOYAGER PAD trial made an impact in the PAD treatment landscape.

Manesh Patel, MD: Amr, what are your thoughts? Larry brings up the COMPASS trial, a huge finding and a home run, but how do you think about it? How does the VOYAGER PAD trial, the revascularization study, add to that? You go from a chronic vascular disease, and believe me I was involved in VOYAGER, we didn’t think COMPASS would be that positive. We thought, COMPASS got a 5-mg dose, twice daily, it was stopped early, and it was positive…. We wondered if we should have had a 5-mg dose without aspirin. Wouldn’t it be great to get people completely off antiplatelets?

Amr Abbas, MD:That’s a great question. Before I get into VOYAGER, Rob Safian, [MD,] and I published a paper in CCI [Catheterization and Cardiovascular Interventions]. We used a lot of NIRS-IVUS [near-infrared spectroscopy and intravascular ultrasound] in the past, and we imaged different vascular beds. NIRS-IVUS is this technology that can tell you how much lipids and how much calcium you have. We looked at all the vascular beds, below the knee, SFA [superficial femoral artery], iliacs, renal, carotid, and subclavian. We found something very interesting, that either we had somebody who had calcium and lipid, no calcium no lipid, lipid but no calcium, and calcium but no lipid. Depending on the vascular bed, it was the different phenotype. That might be a phenotypic explanation for why we have differential impacts. We noticed in the SFA population that there was a heavy calcium in all the plaques to the extent that some authors think that the AHA [American Heart Association] progress of atherosclerotic plaque doesn’t necessarily start in the SFA with the foam cells and the lipid. It’s just a direct muscular calcification, and as we know, calcium is a component of the anticoagulation pathway. When you can tell a patient who has stable PAD [peripheral artery disease] that I have a medicine that can cut your rate of amputations and major adverse limb events [MALE] by 50%, and that you know 1 out of 6 people you revascularize will have a major event within 1 year, whether in their leg or cardiovascularly. The VOYAGER trial asks, what do we do after we revascularize our patients with PAD? Can this novel thought process as you’re alluding to change the outcomes?

And sure enough, VOYAGER didn’t disappoint, similar to COMPASS. It showed that after revascularization, you can have a reduction in major adverse limb events. You can have a reduction in major adverse cardiac events [MACE] within 1 year. Comparing aspirin, the dual antiplatelet therapy [DAPT], moving from that into aspirin and rivaroxaban was a very different way than we practiced. When we put in a stent, we wanted to give them dual antiplatelet therapy. But my way of looking at the disease is completely changing.

Manesh Patel, MD:When we did VOYAGER, we allowed randomization. It was rivaroxaban on top of aspirin or placebo, but you could get clopidogrel. People often say they want to use clopidogrel, and we allowed it. They also say they want to use it for 6 months, not just 30 days. We said it sounds good, you can use it for 6 months. We put an amendment in, and the average use was 31 days, just like Medicare. It’s great to see it was used, it didn’t change outcomes. What was astounding in addition to the effect of the drug was that 19% at 3 years were having a MACE or MALE event. Half of that event rate in the aspirin arm was limb events that patients really fear. Having a revascularization event, there is around a 1 in 5 chance that your patient, 2 to 3 years down the road, will have another limb event. So you go to try to help something, and you might have an ALI [acute limb ischemia] event, or a bigger event, you might have an amputation. Words of caution: we might be intervening on patients, so we must be very careful who we’re intervening on, pick the right patient. If you are going to go to all the trouble of putting a drug-coated balloon, atherectomy, all these fancy technologies, make sure you use the therapy that keeps the artery open for the longest time. Larry, how do you put that in? You think a lot about value. Revascularization is one of those places where we’re spending a lot and thinking about that, how would you assess that?

Larry Allen, MD:One is, if you have a patient in front of you and you sit down with them, often they want the problem taken care of and to not have to think about it. It’s one of the reasons interventions are so popular because you want it fixed. Unfortunately, we know that the biology didn’t just happen at that 1 lesion where you put the stent; the biology is systemic. It’s about having conversations with patients at the beginning on what we think caused this, and what we are going to do long term about it? Just because you had an intervention, doesn’t mean you’re fixed. In fact, the intervention was just a marker that this is going to happen elsewhere. It’s the concept of what we’ve learned from COMPASS and VOYAGER in terms of anticoagulation, but what are the other things that need to happen? That’s a critical conversation, and it should be happening at the time…. Often, we like to pat ourselves on the back that we’ve done something good and, “You can thank me for fixing you.”

Manesh Patel, MD:That’s why intervention is fun, because people feel better and you get that immediate, “Yes, the doctor took care of this.” But what is true on at least the post-procedural therapy, we had studied it much less than what we had studied in the coronary tree. I said there are no references, but a small aspirin, clopidogrel trial called CASPAR was used as sometimes using it, or DAPT from the coronary tree. But we realized as we looked at the data as we unblinded the trial, very different than the EUCLID trial experience, that not only were the findings dramatically different, because their event rates were so high—they’re going through a procedure, and maybe it’s because you’re randomizing them after the procedure—but the bleeding risk wasn’t as high as we would have thought. The dose had been tested, and even with clopidogrel, you got a bit more bleeding, but not a huge efficacy hit. We tell people use whatever you want, just make sure you add rivaroxaban post revascularization if you want to prevent those things at that dose. However, you might choose your patients, and want to choose patients who have endovascular or revascularization, which are easy to find. The surgical patients had an even bigger benefit. Our surgeons are adopting this faster than our cardiologists because surgeons for many years used aspirin or warfarin for that vein graft bypass, so they already had this process in mind.

This transcript has been edited for clarity.