DAPT with Clopidogrel Superior to Ticagrelor one month after PCI: Results from the TALOS-AMI Trial

With the widespread use of second-generation drug eluting stents, it has become more apparent that the risk of stent thrombosis decreases significantly after the first thirty days. The risk of bleeding, on the other hand, increases during that same time period. It has been proposed that de-escalation of potent P2Y12 inhibitors could mitigate that risk of bleeding. Dr. Kiyuk Chang and his co-investigators sought to answer this in the TALOS-AMI trial, the results of which were presented during a late breaking clinical trial session today at the 2021 American College of Cardiology Scientific Sessions.

In this multicenter, randomized, open label trial, patients with acute myocardial infarction undergoing successful PCI were treated initially with Aspirin and Ticagrelor for a total of 30 days. At 1 month after PCI, patients without adverse events were randomized to continue dual antiplatelet therapy with ticagrelor or to switch to clopidogrel. Participants were followed at three- month intervals up to one year. This trial differs from its predecessors as the switch from one P2Y12 inhibitor to the other was performed without genotype testing or platelet function testing. Furthermore, the switch was performed without a loading dose.

The primary endpoint of this noninferiority study was a composite of cardiovascular death, MI, stroke, and BARC bleeding type 2, 3, and 5. To meet a noninferiority margin of 3% at 80% power, the investigators enrolled 2697 participants. Baseline characteristics were similar across the groups: mean age was 60 years, 50% had hypertension and 25% had diabetes. 17% of the participants were women, and approximately 50% of the acute coronary syndromes represented were STEMI. Participants were followed closely for adherence and had an impressive adherence rate of more than 97% in both arms at 12 months.

At 12 months, the cumulative incidence rate of the primary endpoint was 4.6% in the de-escalation arm, and 8.2% in in the control arm, representing an absolute difference of 3.6% (HR 0.55, 95% CI 0.4-0.76). This met statistical significance for both non-inferiority and superiority, with p<0.001 for both. The composite endpoint was driven mostly by bleeding: with a rate of 3.0% in the de-escalation group versus 5.6% in the control group. While there were fewer ischemic events in the de-escalation group (2.1% vs 3.1%), the difference did not meet significance. To assess the safety of switching from ticagrelor to clopidogrel without a loading dose of the latter, investigators assessed ischemic risks in the 2 weeks after randomization and found no deaths or stent thrombosis during that timeframe.

In response to the trial results, Dr. Roxanna Mehran, Director of Interventional Cardiovascular Research and Clinical Trials, Mt. Sinai University Hospital New York, questioned the overall generalizability of the trial, given the specific South Korean population investigated. “Given the lower thrombotic events in South Korea, and the very high adherence to DAPT in this trial, I wonder what similar de-escalation protocols would look like in a more diverse patient population,” she stated.  She did note that similar de-escalation trials are on the way and should show interesting results in the near future.

The authors acknowledged the lower thrombotic event rates in South Koreans as a limitation of their study and added that the incidence of the primary endpoint was lower than they had initially anticipated when compared to similar trials as well.