This transcript has been edited for clarity.
Hi. This is Dr Michelle O'Donoghue, reporting for Medscape. Is aspirin really the cornerstone of antiplatelet therapy? I have to admit that I've written probably countless reviews that have actually led off with that exact wording. But it's interesting now to pause, take a step back, and think about what evidence we have to support that concept—especially now that we have a growing number of trials that suggest that dropping aspirin may in fact be a safe strategy for patients who are at least 1-3 months post percutaneous coronary intervention (PCI).
I think many people have forgotten about the CAPRIE trial because it was published some time ago. It looked at patients with established atherosclerotic disease and compared clopidogrel monotherapy with aspirin monotherapy head-to-head. Clopidogrel offered a significant reduction in major adverse cardiac events (MACE), albeit fairly marginal compared with aspirin alone. But, importantly, it also had the same overall rates of bleeding, and if anything, a lower risk for gastrointestinal (GI) bleeding as compared to aspirin. Clopidogrel offers more cardiovascular benefit in terms of relative risk reduction and may offer the advantage of having less GI bleeding on top of that.
Why didn't clopidogrel monotherapy become the preferred strategy? Well, from there, we had several trials that tested a strategy of a P2Y12 inhibitor on a background of aspirin, because there had long been the belief that aspirin was the cornerstone of antiplatelet therapy. From that point forward, we have been asking at what point should we drop the P2Y12 inhibitor for patients who are on dual antiplatelet therapy (DAPT)? As you are aware, a myriad of trials have been testing the question of dropping a P2Y12 inhibitor and the optimal timing. But now I think we've flipped that around. A growing number of studies have been looking at the concept of dropping aspirin and continuing the P2Y12 inhibitor alone or in combination with an anticoagulant. I've seen in my practice that clinicians seem to be more comfortable with the concept of dropping aspirin for patients who require triple therapy, namely patients who require DAPT (because they are post PCI), and an oral anticoagulant, perhaps because they have underlying atrial fibrillation.
Four studies have looked at the idea of dropping aspirin for patients who are just going to continue on P2Y12 inhibitor monotherapy alone: Global Leaders, Smart-Choice, STOP DAPT-2, and TWILIGHT. The more recent one, TWILIGHT, was published in The New England Journal of Medicine earlier this year. It was the first double-blind trial to really test this hypothesis of dropping aspirin. With TWILIGHT, it was 3 months after PCI and included high-risk patients with acute coronary syndrome. The notable conclusion was that by dropping aspirin, there was a marked reduction in bleeding that did not appear to come at the price of an increased risk for MACE.
When we combine the data across the four trials that have looked at this question, we see a very consistent pattern. Dropping aspirin markedly reduces bleeding, and yet it does not increase the risk for MACE. Why might that be? Some of the in vitro and in vivo data support this concept. When a patient is on potent P2Y12 inhibition, we actually find that it not only blocks platelet activation via P2Y12 dependent pathways, but it also may block thromboxane A2-dependent pathways—the same pathways targeted by aspirin. Adding aspirin on a background of potent P2Y12 inhibition may not lead to further inhibition of platelet activation. That interesting concept may support what we're finding in studies—that by dropping the aspirin, we're not losing out too much because we're still able to offer the same benefit or efficacy of a P2Y12 inhibitor at a price of decreased bleeding.
Are we ready to move this mainstream and have patients on just P2Y12 inhibitor monotherapy after PCI? I think that more and more clinicians are becoming comfortable with that concept. Should this be restricted to patients who have a high risk for Gl bleeding? I think we can look at the types of patients who were enrolled in these trials. But, of course, there are always concerns about generalizability.
It will be interesting to see what direction the guidelines take. I always welcome input from the group as to whether you feel like you need to see more data, when now we've got about 30,000 patients across these four trials that do support the concept that dropping aspirin may be safe.
I do have unanswered questions. We know that clopidogrel has very significant interpatient variability. Would a strategy of clopidogrel monotherapy alone (dropping aspirin) be sufficient if you didn't know whether that patient was a clopidogrel responder ? Also, would you continue P2Y12 inhibitor monotherapy indefinitely? Or would there be some point along the way where you would switch back to aspirin? None of these particular questions have been tested yet in a clinical trial; the clinical trials to date have only looked out to 15 months. Those are some of my remaining unanswered questions.
As always, I look forward to hearing your thoughts. Is P2Y12 inhibitor monotherapy ready for prime time, or do we need more data to help guide us forward? Signing off for Medscape, this is Dr Michelle O'Donoghue.
Michelle O'Donoghue is a cardiologist at Brigham and Women's Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she's never strapped on hockey skates. The opinions expressed in this article are solely her own and do not necessarily reflect the views and opinions of Brigham and Women's Hospital.
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Cite this: Michelle L. O'Donoghue. Dropping Aspirin Post PCI: Are We There Yet? - Medscape - Jan 30, 2020.
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