Update to Chapter 39: Evaluation and Management of Non-ST-Segment Elevation Myocardial Infarction, Chapter 40: ST-Segment Elevation Myocardial Infarction, Chapter 41: Antiplatelet and Anticoagulant Therapy in Acute Coronary Syndromes and Chapter 42: Percutaneous Coronary Interventions in Acute Myocardial Infarction and Acute Coronary Syndromes

Study Summary

The multicenter, randomized, open-label TALOS-AMI trial examined whether de-escalating dual antiplatelet therapy (DAPT) with clopidogrel was non-inferior to continuing with ticagrelor, a more potent antiplatelet medication than clopidogrel, in 2697 stabilized patients with acute myocardial infarction (AMI) who did not experience major adverse events during the first month after an index percutaneous coronary intervention (PCI) using current-generation stents. In the de-escalation protocol, a uniform, unguided approach was taken without any genetic testing; patients were started on clopidogrel 75mg approximately 12 hours after their last dose of ticagrelor without any prior clopidogrel loading.

The primary outcome — cardiovascular death, myocardial infarction, stroke, & Bleeding Academic Research Consortium (BARC) bleeding type 2, 3, or 5 1-12 months after the index PCI — occurred in 4.6% patients in the clopidogrel group compared with 8.2% in the ticagrelor group (P for noninferiority < 0.001, P for superiority < 0.001; see accompanying Hurst’s Central Illustration). A significant decrease in bleeding risk (3.0% versus 5.6%; HR 0.52; 95% CI 0.35-0.77) was noted with the strategy of switching from ticagrelor to clopidogrel 1 month after the index PCI.

Commentary

Study Strengths: The study was a randomized, large, multicenter trial. The two study groups were well balanced in clinical characteristics, lesion characteristics, and number enrolled in each group. Additionally, adherence was very high amongst both study groups (98% adherence in de-escalated group and 97% in control group at 10 months).

Study Limitations: Limitations of this study were its open-label design and the fact that this study was only conducted in South Korea; thus, it is unclear how much the results can be extrapolated to other populations and if they were influenced by genetic variation reducing the effectiveness of clopidogrel. Notably, the CYP2C19 loss-of-function allele is more frequently found in people of East Asian ethnicity than in other ethnic groups.

Next Steps/Clinical Perspective: The results of TALOS-AMI call into question the optimal antiplatelet strategy after myocardial infarction and will require additional investigation before the conclusions are able to be confidently incorporated into clinical practice. The TALOS-AMI team are now planning a follow-up real-world study to review outcome differences between patients similar to those enrolled in TALOS-AMI who either remained on a more potent regimen or were de-escalated. The trial also paves the way for further investigation on alternative antiplatelet therapy for patients who have undergone stenting following a myocardial infarction, specifically in multiethnic populations.

Trial Reference