Expert Perspectives on Managing Polyvascular Disease and Coronary Artery Disease - Episode 5

Dual Antiplatelet Therapy in CAD

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Dr Manesh Patel and other experts discuss the role of dual antiplatelet therapy (DAPT) in treatment of coronary artery disease.

Deepak Bhatt, MD, MPH: Let’s launch into a discussion about dual antiplatelet therapy and antiplatelet monotherapy and dual pathway inhibition. Manesh, I’ll start with you. With coronary artery disease, what did the data tell us for dual antiplatelet therapy?

Manesh Patel, MD: It’s great to remind ourselves. I’ll go through the data, but I’ll give the mental framework I think about when I talk to fellows and colleagues. For many years, we’ve been thinking about vascular disease. It’s a process across all your vessels and across your body, and we’re trying to prevent this thrombotic component. When people have an acute MI [myocardial infarction], when people get a stent, they’ve had a specific event in their vascular territory, in coronary artery disease. For that, we’ve got a long history of data about what antiplatelet therapy does.

Another way I think about it is that sometimes you have a pothole problem, and sometimes you have a highway problem. Most of the time, we’re working on the highway, but sometimes you have a pothole. When the pothole has a problem—we have to put a stent, we’ve had a heart attack—then we use more antiplatelet therapy. At some point, that pothole is OK. Then I worry about the whole highway. I bring that up because when I’m thinking about dual antiplatelet therapy [DAPT], or antiplatelet therapy in general, we have a history of going through the trial data. The CAPRIE trial over 20 years ago for chronic vascular disease, used aspirin vs clopidogrel, and they seemed to be about the same. Clopidogrel was better in 19,000 patients, about an 8% relative risk reduction at a 5% rate. It did reduce CV [cardiovascular disease] death and mind stroke, but it was costly. For that little benefit, most patients didn’t switch from aspirin to clopidogrel. The guidelines, interestingly, recommended either.

When we started thinking about the CURE [Clopidogrel in Unstable Angina to Prevent Recurrent Events] trial, where we had patients with a heart attack, we thought, “If you put an extra antiplatelet, the potholes rupture. Regardless of whether we put a stent, they seemed to do better in the long term.” That was for a year. It wasn’t for 20 years. We started to realize that we can treat these patients longer, and the trial had patients on it longer. You led CHARISMA, which was clopidogrel and aspirin on top of aspirin. Interestingly, in that trial, dual antiplatelet therapy had an 8% or 10% reduction—you’ll probably tell me the exact number; I hate to misquote your data—but it didn’t meet statistical significance, and there was at least an increase in moderate GUSTO [Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries] bleeding. Now we start thinking about this as a risk-benefit analysis. Historically, antiplatelet therapy is good, especially for this pothole problem. We’re going to use 2 when I have to. But most of the time, for chronic disease, we don’t have to use 2.

In 2005, 2006, as Eric Secemsky talked about, we had a seminal event. As interventionalists, we got these drug-eluting stents, and we thought, “We’re going to help our patients.” We started putting drug-eluting stents in all these patients. I remember being a fellow and thinking, “These are awesome.” In 2006, there was the first report of late stent thrombosis. We started thinking, “We’ve been putting these devices in patients who may have long-term problems.” The pothole wasn’t healing. Maybe there would be another clot or problem. I remember a faculty member at Duke University saying, “If you ever put a stent in me, I want dual antiplatelet therapy for my whole life plus 1 day.”

We trained everyone. Stent doctors were saying, “Take these 2 drugs and don’t stop. You’ve got to know that.” The technology has gotten better. The DAPT trial came out and said, “Because of this problem, we need to know how long, and there are risk scores and balances.” But the big message is that there’s a risk-benefit analysis. It’s not so overwhelming that everyone should get it. My take-home message from all these complicated data is that for coronary artery disease, when there’s a pothole problem, acute MI, or a stent, we have to use dual antiplatelet therapy. We’ll talk about how long, but at some point we’re going to talk about switching to thinking about the whole highway and treating the vascular disease.

Deepak Bhatt, MD, MPH:Those are really good points.

Transcript Edited for Clarity