The Role of Combined Antiplatelet Therapy


Key opinion leaders discuss the available antiplatelet therapies for CAD/PAD.

James Groce III, PharmD: Regarding secondary prevention in CAD [coronary artery disease] and PAD [peripheral artery disease], the last question I would have for you—and you’ve alluded to it, but if you could just remind our audience—is “What is the role of combined antiplatelet therapy in patients who have CAD/PAD?”

Paul Dobesh, PharmD: Yeah, I think this is something that there is a little confusion about as we go longer term. So, as I stated, if a patient has an acute coronary syndrome, they should be getting dual antiplatelet therapy [DAPT] for a year. If a patient who has stable ischemic heart disease ends up getting PCI [percutaneous coronary intervention], they get one of today’s second-generation stents; they should be on dual antiplatelet therapy for 6 months. That’s the grade 1A recommendation. That is not negotiable. Now, in my practice—and I’m guessing in yours, as well as in those of many others who may be listening today—a number of times we will have this discussion, or we’ll hear from cardiologists who say, “OK, yeah, they’ve finished the year.” You know, the patient comes in and it’s been 15 months. Really, the thought is almost like “All right, well, we’ll just keep going. They can pay for it; they’re not having any problems. I’m just going to keep them on dual antiplatelet therapy.” The question I ask to that is “To what end?” Right? Because extended dual antiplatelet therapy beyond a year is a level 2B recommendation, which is really the lowest level of recommendation—that means it’s possibly helpful. Not probably helpful, not definitely helpful, but it’s possibly helpful.

What’s fascinating to me is when you look at the data. The data for this very low-level, continuing long-term DAPT therapy—dual antiplatelet therapy—come from the DAPT trial. Really, if you look at the patients who get today’s second-generation everolimus stent, which is the most commonly used stent—it’s the most commonly used stent in the world, in the United States—the absolute benefit of reducing ischemic events is about 0.6%, and it reduces MI [myocardial infarction]; that’s it. It has no effect on cardiovascular mortality and has no effect on stroke; no DAPT trial has ever had an effect on stroke. There’s a small modest reduction of myocardial infarction, which was coupled with about a 0.4 increase in major bleeding. So the absolute net clinical benefit of long-term DAPT is actually fairly small. But yet we see a lot of people who are saying it’s working, and you don’t mess with it. So, for that patient, I think we have to ask ourselves, “Can we do better than this?” To what end are you just continuing DAPT indefinitely? In the coronary patient, I think that it’s a big question of after a year, what are we going to gain? If you actually look at the evidence, it’s not a lot. There is some reduction in MI, but that’s about it.

For peripheral artery disease patients, there is really no role outside of an intervention, and even then, I don’t think there’s a strong recommendation one way or the other. Usually if they get a stent, if they’re to use dual antiplatelet therapy, it’s usually secondary to stent. You have to remember that when we’re stenting a vessel in the legs, these vessels are much larger than a coronary artery. Coronary arteries are 3 mm to 4 mm. Peripheral arteries can be a half inch. So the risk of restenosis and the risk of other kinds of complications is much smaller because we’re dealing with much larger vessels. So the use of dual antiplatelet therapy. Most time if they do it, they’ll do it for about 6 months and that’s it. But once again, as I stated previously, there’s no specific guideline that really drives that this is what you have to do after a stent in the peripheral arteries.

James Groce III, PharmD: I’m glad you did emphasize not just the outcome of efficacy but also certainly the outcome of safety, because I think that’s the part that sometimes goes missing. In our efforts to improve the outcome of our patient, we focus so much on the outcome of efficacy, but often at a price of safety. I think that’s where so many of us perhaps have been burned in our patient populations that we see and our role as providing care that those patients who go beyond the guideline recommended duration of therapy get really, at that point, no real continued positive benefit, but we begin paying a tremendous price with respect to the outcome and potential for increasing, particularly with dual antiplatelet drug therapy, the bleeding potential.

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