Load It to See It: Prasugrel in NSTEMI

Interview | At the 2014 American Heart Association at the Institute of Cardiology, Paris, France, CardioSource WorldNews: Interventions spoke with Dr. Gilles Montalescot, MD, PhD, and chair of the Department of Cardiology at Pitié Hospital. In this interview, Dr. Montalescot sheds light on the effect of prasugrel pretreatment strategy and the great debate of dual antiplatelet therapy. Those in the field know that following PCI for non-STEMI, a P2Y12 antagonist, is recommended for one year—but what about pretreatment? As of ESE in 2013, there were some surprising results from ACCOAST-PCI.

CSWN: Dr. Montalescot, you did the original presentation—and I believe it came out of The New England Journal?


So let's talk about the original ACCOAST results before we get into what's coming up in JACC. What did you find?

Initially, what we looked at is that NSTEMI is presented to the Emergency or the Cardiology Department being randomized for pretreatment with prasugrel immediately at presentation versus no treatment when you decide for invasive strategy within 48 hours. And what we found is actually: Pretreatment—even with one of these new drugs, very potent, hyperly active—did not protect the patients better against ischemic events on; actually, the number of ischemic events was exactly the same in both arms.

Did that kind of surprise you?

Yes, because we lived with the idea that pretreatment was good, coming from cures performed almost two decades ago. And that was a different—a whole different—issue. [With] conservative management, patients didn't go to the cath lab easily, [with] very few PCIs. That was performed on only 20% of patients. So it's a different story. A different era, also.

[In your paper appearing in] the December 23rd issue of JACC, what were you looking at?

Actually, we had more bleeding. But no efficacy with pretreatment. So we were—

You had the cost but you had no—nothing—no value for the cost?

There was only harm ... We started by giving the drugs early on [but] there was more bleeding and no benefit. Exactly the same story. And that was a surprise to us: no benefit at all. And, of course, in this population, [this] wide population, 30% of patients didn't have PCI. And [with] those going to cabbage surgery: no benefit of pretreatment. So it was medically treated. And those with normal coronaries after angiograms: no benefit.

So it was very important to look at a PCI subgroup of patients because, if anything, pretreatment has been invented for PCI. We want to have full treatment, effective treatment, when we inflate the balloon.

Well, in the editorial comment that accompanies your paper, the authors say it's rather remarkable that the best timing for the initiation of P2Y12 inhibitors in STEMI has not been really clearly established up until now.

It's quite right. Even with clopidogrel, we do not have a randomized study like ACCOAST to say pretreatment is good or bad. So, you know, it's in the guideline; we have recommendations for pretreatment but no study, no randomized study for pretreatment. We have a cure, which was not in a study of pretreatment versus no pretreatment. We have CREDO—all of the patients were treated after the coronary angiograms, so this is not a study looking at pretreatment. We have no study with ticagrelor. And this is the first study with prasugrel.

So the editorial commentary, I believe, and part of the title is "Loading After Seeing." Is that kind of the bottom line here?

It's exactly what we should do. Especially when you work in a high-volume center, when you send a patient to the cath lab rapidly within 24 hours or 48 hours, you can wait. Nothing is going to happen during this waiting period. And you are not going to pretreat and overtreat many patients who do not [merit] the treatment.

So, in terms of the debate going on here at AHA, in terms of dual antiplatelet therapy: I know [that] in Europe, some of the standards are not to go necessarily for a full year, to maybe, sometimes, go a little less. Now, after some of the results here, what are you going to do?

It's a different question. I think in 2014, we have had great news, and we see clearly what we should do with antiplatelet agents. First, avoid pretreatment in non-ST elevation ACS, for sure, and stable patients, for sure. Look at the coronaries first.

When you start treatment, you have to continue for a period of time. Will that be six months? Twelve months? Twenty-four months? Thirty months? For life long? Nobody knows, and I think there is no magic number. If you have a high-bleeding risk patient, six months is fine. We have now seven studies, randomized studies, all too small, but all together they say, "Less bleeding—if you treat for six months, no downside for ischemic events."

But for secondary prevention? Longer treatments, longer than a year? The DAPT tells us that actually you may benefit for MI and stent thrombosis with a very long treatment. So [with] selected patients [who have] no excess bleeding risk and probably high ischemic risk would make the point for a long treatment.

Keywords: CardioSource WorldNews, ACC Publications

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