TWILIGHT: A randomized trial of ticagrelor monotherapy vs. ticagrelor-plus-aspirin beginning at 3 months in high-risk patients undergoing PCI

Reported from the TCT Congress 2019 in San Francisco - USA

At TCT 2019 in San Francisco - USA, Roxana Mehran presented the results of the TWILIGHT trial. Salvatore Brugaletta provides a summary of the key messages.

The methodology

Monotherapy with a P2Y12 inhibitor is an emerging approach to reduce the risk of bleeding after PCI, especially in those patients with high bleeding and ischemic risk. The Twilight trial examined the effect of ticagrelor alone vs. ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding of an ischemic event. Event-free patients were randomized 3 months after PCI to one of the two arms and they were followed for 12 months (15 months after PCI). The primary endpoint was BARC 2,3 or 5 with superiority of ticagrelor alone vs. the other arm treatment. Secondary endpoint was a composite of any-cause death, nonfatal MI or nonfatal stroke, with noninferiority hypothesis.

What were the results?

A total of 7119 patients were randomized. Between randomization and 1-year the incidence of primary endpoint was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin with superiority met. Non-inferiority was also met for the secondary endpoint. The authors concluded that among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke.

My take on this study

The authors and investigators of this trial should be first of all congratulated, as the study was really well done with high rate of follow-up.

It was quite obvious that without aspirin there is a reduction in terms of bleeding, but it is interesting to see that this does not translate in an increase of the ischemic risk of these patients. This is proof of the benefits of the current generation DES.

Some points are interesting for discussion.

It opens, for example, the debate on how to select the best patient for ticagrelor alone. What to do with a patient 6 months after PCI on clopidogrel and aspirin who fulfils criteria of high bleeding risk? Are we comfortable enough to drop aspirin and to change from clopidogrel to ticagrelor in such patients?
Another interesting point is may we reduce even more the window of the 3 months before dropping aspirin? In patients under OAC or NOCA, European guidelines recommend to use aspirin only peri-PCI and then to have only a single P2Y12 inhibitor. So next step will be to have trial comparing conventional DAPT vs. mono APT since the beginning.
Eventually, given the recent demonstration of superiority of prasugrel over ticagrelor, may we expect the same findings by using prasugrel as monotherapy?