Antiplatelet Therapy in Coronary Artery Disease

HCPLive: Could you review the 2016 ACC/AHA guidelines focused update on duration of dual antiplatelet therapy in patients with CAD?

Bhatt: With respect to dual antiplatelet therapy guidelines, both sides of the Atlantic generally say six months of dual antiplatelet therapy for elective stenting, but for patients who have acute coronary syndromes treated with or without stenting in general, it’s 12 months. That's the anchor with a class 2b recommendation to continue longer, meaning it can be considered though but isn't obligated. And it should be considered, I think, but in patients that are at low bleeding risk only. If patients are at high bleeding risk, I think prolonged DAPT is a bad idea, beyond what the guideline recommendations that I just said were.

In particular, even if a patient's at high ischemic risk and high bleeding risk too, high bleeding risk trumps. So I wouldn't recommend prolonged DAPT, but again, antiplatelet monotherapy is the way to go there. Now, patients that are at high ischemic risk and a little bleeding risk, that's a different story. That's where I think protracted DAPT can be considered or should be considered in appropriately selected patients.

HCPLive: What is the mechanism of action of antiplatelet agents in the management of coronary artery disease?

Bhatt: The primary antiplatelet agents—at least on an outpatient basis, the one we consider of course is aspirin. That's the most commonly used, familiar, cheapest, antiplatelet agent, and for chronic therapy, 81 milligrams a day is probably the way to go. My own preference is not enteric-coated, but I do know enteric-coated is highly prevalent. A little bit of data suggests that that might interfere in some patients with the absorption and appropriate antiplatelet effects. But in general 81 milligrams a day I think it’s the way to go for chronic therapy. Of course, in an acute setting you want to load with about 62 or 325, but in general chronic therapy, 81. That reversibly inhibits the platelet for its lifespan of 7-10 days.

As far as the other broad category of oral antiplatelet, I refer to oral ATP receptor antagonists namely clopidogrel, which is now generic and most folks are familiar with, but also which is going into multiple generic forms these days. So the price is dropping there. And then ticagrelor, which is also an ATP receptor antagonist. Prasugrel and ticagrelor are more potent than clopidogrel, and clinical studies show that at least for patients with acute coronary syndromes, they may appear to be better.

Prasugrel, specifically, better applies to ACS treated with stents, and for ticagrelor, that better applies for ACS, where in the PLATO trial, ticagrelor was found to be superior to clopidogrel, and including lower cardiovascular mortality. So for that reason, some have favored ticagrelor as the preferred antiplatelet on top of aspirin in patients with ACS for a year, at least. In the PEGASUS trial, with ticagrelor, a lower dose than the ACS dose, 60 milligrams, the idea of ticagrelor 90 BID being the dose for that first after ACS. But in PEGASUS, patients with prior MI—1-3 years prior—there was a benefit of ticagrelor 60 PID when added to aspirin versus aspirin alone in reducing ischemic events in all cases.

Intensifying the regimen raises major bleeding risk, but in those populations, at least it seems to be worth it that there's a reduction in important ischemic events, even beyond the year after ACS. So in general, I'd say for ticagrelor, it's got the most data and in some respects, the most robust data. And the most recently we've added to that with THEMIS and THEMIS-PCI.