De-escalation DAPT therapy after 1 month in MI patients with PCI reduces primary outcome

A Prospective, Multicenter, Randomized, Open-label Trial To Compare Efficacy And Safety Of Clopidogrel Versus Ticagrelor In Stabilized Patients With Acute Myocardial Infarction After Percutaneous Coronary Intervention – The TALOS-AMI trial

Presented at ACC.21 by Kiyuk Chang, MD, PhD (Seoul, South Korea)

Introduction and methods

In stabilized patients after an acute MI, who have taken and well-tolerated dual antiplatelet therapy (DAPT) consisting of aspirin plus ticagrelor for 1 month, de-escalation of DAPT with clopidogrel may be non-inferior to DAPT with ticagrelor for the net clinical outcome.

The design of the trial was as follows. AMI patients who underwent successful PCI and who had no adverse events after 30 days of aspirin plus ticagrelor entered the trial and were randomized to the de-escalation group (aspirin plus clopidogrel) (n=1349) or the active group (aspirin plus ticagrelor) (n=1348) for 12 months. ~54% Of patients in the study population had STEMI. The primary endpoint was a composite of CV death, MI, stroke and BARC bleeding type 2, 3 or 5.

Main results

• The event rate for the primary endpoint was 4.6% in the de-escalation group vs. 8.2% in the active control group (HR 0.55, 95%CI: 0.40-0.76, Psuperiority<0.001).
• There was no difference in the ischemic outcome of CV death, MI and stroke between the two groups.
• The composite of BARC bleeding type 2,3 or 5 was lower in the de-escalation group compared to the active control group (3.0% vs. 5.5%, HR 0.52, 95%CI:0.35-0.77, P<0.001).
• The composite of CV death, MI, stroke and BARC bleeding type 3 or 5 was reduced in the de-escalation group compared to the active control group (2.8% vs. 4.9%, HR 0.58, 95%CI: 0.38-0.87, P<0.009).
• Comparison of event rate in the TALOS-AMI trial to that in other major de-escalation trials (including Twilight-ACS, TROPICAL-ACS, HOST-REDUCE-POLYTECH-ACS and PLATO) for ischemic outcomes 1-12 months after PCI showed similar results and in none of the trials an increase in ischemic outcomes was observed with de-escalation. Also, similar rates for bleeding outcomes were observed in all the trials.

Conclusion

The TALOS-AMI trial in an uncomplicated AMI population demonstrated that de-escalation of therapy with clopidogrel (clopidogrel plus aspirin) 1 month after PCI resulted in a decrease of the primary composite outcome compared to the active control group who received ticagrelor plus aspirin. These results suggest that these patients are a good candidate for de-escalation strategy.

Limitations of the study that were mentioned by Chang were: open-label and not placebo-controlled, and that the trial was only conduced in South Korea.

Discussion

The discussant Claire Duvernoy, MD (Ann Arbor, MI, USA) believes that this trial has major implications for practice. The strategy of de-escalation is already being used, at least in the USA, for reasons of costs, tolerability and safety. But now it has been demonstrated that it is safe and effective. She would like to hear more though how common this strategy is in Korea and she wonders how generalizable these results are for other ethnicities, with possible different bleeding and thrombotic risks. She thought it was interesting to see that although CYP2C19 LOF mutations are common in Korea, clopidogrel was effective in reducing ischemic outcomes. And she was glad platelet function was not performed in this study, because it is not part of routine care and this gives confidence that platelet testing is not per se necessary when giving clopidogrel.

- Our coverage of ACC.21 is based on the information provided during the congress –