Requiem for Aspirin in Dual Antiplatelet Therapy?

Hi. This is Dr Michelle O'Donoghue, reporting for Medscape. I'm here at the Transcatheter Cardiovascular Therapeutics (TCT) conference in San Diego, and one topic that keeps coming up for discussion, with people on very different sides of the issue, is the optimal duration of dual antiplatelet therapy (DAPT). But the twist that I'd like to put on this topic today, and hear people's thoughts on, is whether we should be thinking about it differently. This isn't really a question of extending treatment with a P2Y12 inhibitor, but about whether we should be considering dropping aspirin from a DAPT regimen sooner.

I would argue that when we look at the weight of the evidence overall, several trials have compared longer durations of DAPT with a P2Y12 inhibitor compared with shorter durations. Particularly in acute coronary syndrome (ACS) patients, we tend to see that by prolonging DAPT we reduce the risk for ischemic and thrombotic events, but that it comes at the price of increased risk of bleeding. It is intriguing that the same is not exactly true when we drop aspirin from a DAPT regimen, although so far, evidence is fairly limited.

A few years ago we had the intriguing findings from WOEST that were published in the Lancet.^[1] This was an open-label and fairly small trial of triple therapy for patients who had an indication for oral anticoagulation. It suggested that by dropping aspirin from a triple-therapy regimen after a month, not only could we reduce the risk of bleeding, but we may in fact have a signal toward a reduced risk for ischemic events.

We now have the results of the GLOBAL LEADERS trial,^[2] which were presented at European Society of Cardiology in 2018 and also published in the Lancet. Some have criticized the trial for having a somewhat complicated study design, but I would still say that the findings are quite intriguing. More than 15000 patients were enrolled post–percutaneous coronary intervention (PCI), and the experimental arm was 1 month of DAPT with ticagrelor and aspirin and then 23 months of ticagrelor monotherapy. Aspirin was dropped in its entirety. Meanwhile, the control arm was DAPT for the course of a year followed by aspirin monotherapy.

One might argue that a noninferiority design would have been interesting enough to suggest that ticagrelor monotherapy was not inferior to a standard DAPT regimen. But what the findings showed was even more intriguing. At the end of 2 years, there tended to be a strong trend toward a reduced risk for ischemic events—specifically death or Q-wave myocardial infarctions—for patients treated with ticagrelor monotherapy. Although this was just shy of statistical significance (P = .07), when one looked at the results at the 12-month mark, these were actually statistically significant. I think that pausing right there is really quite fascinating. Basically, a 12-month regimen of ticagrelor monotherapy, once the aspirin was dropped after the first month, actually reduced the risk for ischemic and thrombotic events when compared with a standard regimen of DAPT.

Yes, the study design is quite complicated and I think it will be important to continue future studies. Other studies, such as TWILIGHT, are ongoing to look at this question of dropping aspirin earlier from DAPT regimens. But what I find very interesting overall is that the weight of the evidence seems to support the idea that by dropping aspirin, not only do you reduce the risk of bleeding, but there is actually no clear signal toward an increased risk for ischemic or thrombotic events. Some would argue that this is at odds with the results from COMPASS,^[3] which suggested that a low-dose anticoagulant in combination with aspirin may be beneficial as opposed to an anticoagulant without aspirin. But I don't want to confuse the topic by bringing in too many different patient populations.

I'm interested to hear your own patient practice. When are you dropping aspirin? Are you? For a patient who requires triple therapy, I've been hearing that more and more people are comfortable dropping the aspirin earlier and earlier, especially for patients who are at increased risk of bleeding. But I'm also interested to know whether anyone considering shorter durations of DAPT is dropping the aspirin rather than dropping the P2Y12 inhibitor. As further trial results and evidence continue to mount, we will also have to see whether this shifts the perspective of guidelines as to whether we should be dropping one versus the other.

This remains a very controversial topic. As always, I'm interested in your thoughts and I look forward to hearing from you. Signing off for Medscape, this is Dr Michelle O'Donoghue.