Regimen Intensification in Polyvascular Disease

Deepak Bhatt, MD, MPH: To close this segment, Marc, I’ll turn to you to give us the big picture. You’ve got a patient with polyvascular disease. Let’s say it’s CAD [coronary artery disease] and PAD [peripheral artery disease]. We’ll get into the antithrombotic strategies in a bit, but what would you do in terms of intensifying their overall regimen? What should we be shooting for in terms of LDL [low-density lipoprotein] or triglycerides, or if they have diabetes glucose or blood pressure? What are the best targets in your opinion?

Marc P. Bonaca, MD, MPH: That’s a great question, Deepak. Putting some of these comments together, what I see in the guidelines as they’ve evolved is further risk stratification. We had a couple of tools in the toolkit and treated everyone the same way. Now that we understand there’s heterogeneity in the diseases and how they manifest, and that there may be different responses to therapy, we have to tailor. For your question, a patient with polyvascular disease, coronary disease, and peripheral artery disease is someone who’s at high risk of not only heart attack and stroke—as Eric Secemsky had said—in the oftentimes fatal events but also major adverse limb events. We need to start thinking about what therapies modify both of those, the totality of the disease, because we’re treating the patient, not the procedures. We’re trying to reduce their risk. For those patients, there’s further risk stratification. Have they had a prior MI [myocardial infarction]? Have they ever had a revascularization of their limbs or have an amputation? Those things help us understand their risk profile. Particularly for patients who’ve had either coronary or peripheral procedures, they’re extremely high risk.

In my practice, and the data would support this, I don’t think a single antithrombotic is enough. I think about it like in the days of aspirin for A-fib [atrial fibrillation]. We used to think that was OK. For polyvascular patients, high-risk patients, it’s no longer OK to use a single agent. It provided acceptable bleeding risk, but they’re so high risk for recurrent events. We need to add something else, and we have data—depending on the specifics of the patient—for adding something directed at thrombin, like rivaroxaban. There are some data for dual antiplatelet in patients with prior MI and prior revascularization from THEMIS and other trials. We’ll get into that, but you need to do something for the thrombotic risk that Manesh talked about.

These patients are exquisitely sensitive to lipid lowering. Just being on a statin isn’t enough. Many patients fail that already, and clinicians have failed them in getting them on a statin. But 70 mg/dL is not OK if you have polyvascular disease. The European guidelines are pushing lower levels of LDL, supported by ODYSSEY Outcomes and other trials, lowers better for everyone, particularly for these patients. They should be as low as possible. For diabetes therapies, they benefit from additional agents beyond glucose lowering, and there are good data for GLP1 [glucagon-like peptide-1] agonists and SGLT2 [sodium-glucose co-transporter 2] inhibitors and from a lot of work you’ve done. I do think we have to do more for these particular patients in all those areas.

Deepak Bhatt, MD, MPH:Those are great points. We’ll home in on the antithrombotic part in the next segment. I just want to underscore some of what you said. To summarize what you said in layman’s terms is, these are patients, the cardiovascular folks—once you identify them—who are very high risk. We want to throw the kitchen sink at them in terms of lifestyle modification. They really do need to watch their diet. It’s not just the usual—they need to watch their weight, get exercising. In terms of pharmacy, it’s most often going to be polypharmacy, so they need to understand that they need to be on all these medicines. That can entail a fair amount of cost as well.

Amy, I’m glad you brought up the issue of disparities because that really amplifies disparities. When we say there’s a cost issue, it isn’t a cost issue for everybody. Some people can afford all those co-pays. But many cannot, and that often exacerbates disparities and care. I’m glad you brought that up, but these are patients who we have to be very aggressive about and make sure they understand the reason why, even if they’re feeling OK in that minute. In the REACH [Reduction of Atherothrombosis for Continued Health Registry Study] data that you cited, it’s remarkable that outpatients, if you follow them for long enough, have extremely high rates of ischemic events and recurrent ischemic events. These are patients who, when they’re identified, want to watch them closely and treat them aggressively.

Transcript Edited for Clarity