Dual Antiplatelet Therapy: The Long and the Short of It

Seth Bilazarian, MD; Gilles Montalescot, MD, PhD


December 05, 2014

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Four Trials with Different Answers

Seth Bilazarian, MD: This is Seth Bilazarian from on Medscape, coming to you from the American Heart Association meetings in Chicago. We have just come from the dual antiplatelet therapy (DAPT) sessions, with four headline presentations of the late-breaking clinical trials,[1,2,3,4,5,6] with conflicting information for physicians who practice in community medicine as clinical or interventional cardiologists. These four trials compared different durations of therapy. I won't go into detail, but each trial compared a shorter duration of DAPT with a longer duration. The answers provided by the four trials to the question of whether longer is better than shorter were yes, no, no, and yes. So, just looking at the headlines, it's very confusing.

Dr Gilles Montalescot from Paris is with me today. He gave the commentary at the session today, and he said many things that help clarify and edify our thinking about this. I took pictures of Dr Montalescot's slides and posted them on my Twitter feed. They are also posted on the ACTION-COEUR Web site. I would like to ask him to renew our current understanding about benefits of short- vs long-duration therapy and how we should think through this.

A Price to Pay for Longer Duration

Gilles Montalescot, MD: It's a difficult question. The two European studies[3,4] looked at shorter-duration of therapy (6 months vs 12 months or 24 months). The idea of a shorter-duration of therapy is to hopefully see a better safety profile. However, both studies were unable to show a reduction of major bleeding. These results were a little bit disappointing, but altogether with the five previous studies[7,8,9,10,11] looking at the same question, we have a significant reduction of major bleeding in a meta-analysis.[12] Finally, I think the hypothesis is verified. When you shorten the duration of treatment compared with 12 months, you are going to have fewer bleeding complications. The next question is whether you have a price to pay on the side of stent thrombosis or myocardial infarction, and the answer is no. All of these studies have shown that the risk was the same on the ischemic side. This is good news, and it supports the European guidelines, which say that 6 months is enough. You don't have to go up to 12 months.

The problem comes with the DAPT trial.[5,6] We are looking at 30 months vs 12 months, and we have a benefit on the ischemic side, but this is a totally different question. We are looking at secondary prevention in a highly selected population, because, of course, the patients who bled during the first year or the patients who had stent thrombosis, or myocardial infarction, or stroke were excluded, and sometimes even patients who did not have these events were excluded because the physician said, "I cannot randomize this patient because he has a Taxus [Boston Scientific, Marlborough, MA] stent in the left main coronary artery. I don't like it. I don't want to run the risk of single antiplatelet therapy at 1 year in this patient." So, it was a highly selected population, and in this population, when you take the time (30 months of follow-up), you see a difference—a reduction of myocardial infarction and a reduction of late stent thrombosis, but you have to pay the price in excessive bleeding complications—not always major bleeding, but significant bleeding complications.

Dr Bilazarian: To summarize, if the main goal is to prevent stent thrombosis and we are using a modern, late-generation stent, using 6 months of therapy, we should be very confident that we are not doing harm to the patient and that the ischemic risk is low. Stent-thrombosis risk is low by stopping, and by continuing, there is a bleeding hazard.

Dr Montalescot: Yes.

Dr Bilazarian: In your commentary, you said that a paclitaxel-coated stent is a risk for stent thrombosis. We are not using those stents. Do you have any other thoughts about that?

Dr Montalescot: There was a full presentation on this cohort of patients with paclitaxel stent[1,2], and they were treated with prasugrel [Effient, Lilly/Daiichi-Sankyo] [and aspirin] vs aspirin alone in the DAPT study beyond 12 months, and there was a dramatic reduction of stent thrombosis and myocardial infarction. The event rate in this part of the study was higher than in the rest of the study. These stents are not the best ones that we have, but we have patients out there with paclitaxel-eluting stents. What should we do with them? Good advice would be keep them on DAPT maybe for a very long period of time, if not for life. Unless they have a bleeding issue, keep them on treatment.

Extended DAPT is Secondary Prevention

Dr Bilazarian: Could you expand on what you said earlier about secondary prevention? In a patient who doesn't have an interventional reason for long-term DAPT (such as left main or bifurcation stenting) but who has a heavy atherosclerotic burden—for example, single-vessel stenting with multiple 50% lesions in another vessel or a patient with peripheral arterial disease or cerebrovascular disease—using DAPT seems to make sense, and what you are saying is we are not using a DAPT for stent thrombosis, we are using it in the long run for secondary prevention. Is that prudent? Is that reasonable? What are your thoughts there?

Dr Montalescot: That is exactly the message. A stent is one thing, but the patient is a different thing, and if you put the DAPT trial data in context, we have data from such other studies as CHARISMA[13] showing that patients with extensive atherosclerotic burden benefit from DAPT, as well as patients with a previous myocardial infarction. If you look at TRA 2°P-TIMI 50[14] or even TRILOGY[15] with prasugrel, you see the curve diverging over time with secondary prevention when you use a longer treatment with double therapy. We need to understand better which patients benefit from longer treatment with two agents, but clearly, extensive coronary disease, peripheral arterial disease, previous events anywhere in the vascular bed, or previous myocardial infarction are probably good indicators. Next year we will have PEGASUS[16] looking at this very specific issue, and patients with a previous history of stent thrombosis should be kept on dual treatment. Intuitively, physicians know very well who these patients are, and if you put four 2.5-mm stents in tiny arteries, these patients are probably better off with two agents for a long period of time.

Personalize the Decision

Dr Bilazarian: American physicians have now been ingrained to use DAPT for 1 year, not just for drug-eluting stents, but for drug-eluting stents in the setting of acute coronary syndrome. Do you have any comment on that? Is there a reason why we shouldn't take the European lead on that?

Dr Montalescot: The European guidelines are fine if you look at bleeding during the first year, and with a shorter duration of treatment, you have a reduction of this bleeding risk because you are shortening the time of treatment with two agents during the first year. If bleeding risk is not an issue and the patient is at high ischemic risk, continuing DAPT is fine. Keep the patient on treatment, maybe for 30 months as in the study or for longer, but we need to personalize the decisions. We have to decide what to do according to the patient profile.

Both types of studies are very useful. Imagine that you have a patient with cancer. We used to say wait a year for this operation. The data that we have from the European studies say you can stop at 6 months, probably even at 3 months with the new-generation stents, and do the surgery. It is the same for patients with atrial fibrillation who need oral anticoagulation. You don't have to wait a year to provide them with oral anticoagulation. You can stop DAPT earlier. If bleeding is not an issue, but the ischemic risk is an issue, DAPT is very useful, and we do a better job with a longer treatment of protecting patients against ischemic events.

Dr Bilazarian: You have just done a fantastic job again, and I will point our audience to your resources and web site. There is a lot of anxiety for physicians who care about and love their patients and want to do the right things. We are trying to reconcile a high ischemic risk and a high bleeding risk and do the right thing. We are enthusiastic, but when we get these conflicting messages from trials, trying to sort through it is difficult. You make the commonsense recommendation to individualize it for patients, engage them, and try to explain as best we can what we are trying to achieve with the ischemic risk and the bleeding risk. Being able to have data that say this is a safe and reasonable thing to do makes me greatly satisfied that we are headed in the right direction, so thank you, Dr Montalescot, for joining me here at the AHA and putting in perspective the important decision making around prolonged DAPT and the safety of shorter duration of therapy when appropriate. Until next time, I'm Seth Bilazarian from the AHA in Chicago.


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