TALOS-AMI: Exploring outcomes after switching to clopidogrel versus ticagrelor at 1 month from MI

The open-label, non-placebo controlled TALOS-AMI study raises the hypothesis that net outcomes (i.e. bleeding and ischaemic) may be similar in selected patients by switching at 1 month from myocardial infarction (MI) [1].

The risk of thrombosis is highest in the first 30 days following acute MI. Bleeding is also higher; however, the curve may be less steep depending on patient bleeding risk and experience with prior antithrombotics,  (see Figure) [2]. Currently, patients who have experienced acute MI followed by PCI receive DAPT with aspirin and a P2Y12 inhibitor. It was unknown whether de-escalation to a less potent, more variable  P2Y12 inhibitor following the 30-day post-PCI would be associated with less bleeding.

Figure: The risk of thrombosis versus bleeding following acute myocardial infarction [2]



The TALOS-AMI trial (NCT02018055) aimed to address this question. The open-label study, presented by Prof. Kiyuk Chang (Seoul St. Mary’s Hospital, South Korea), compared outcomes of 2,679participants who, after 1 month of taking aspirin plus ticagrelor following acute MI and PCI, were randomised to clopidogrel (n=1,349) versus ticagrelor (n=1,348). Participants were monitored for 11 months (i.e. 1 year following MI and PCI).

The primary outcome was a composite of cardiovascular death, MI, stroke, or bleeding academic research consortium (BARC) bleeding type 2, 3, or 5 between 1 month and 12 months post PCI. At 1 year, 59 (4.6%) primary outcome events had occurred in the clopidogrel group compared with 104 (8.2%) events in the ticagrelor group, yielding a hazard ratio of 0.55 (95% CI 0.40–0.76; P<0.001 for both non-inferiority and superiority).

Prof. Chang and colleagues concluded that in patients who had experienced AMI and had no adverse events in the first month following PCI, a de-escalation DAPT strategy in selected patients switching from ticagrelor to clopidogrel was associated with lower net outcomes versus continued DAPT using ticagrelor. This observation was driven mostly by non-severe bleeding events, and power to distinguish a cost in terms of ischaemic outcome was limited.

The researchers acknowledged that this trial had significant limitations; it was open-label and not placebo-controlled. In addition, it was underpowered to detect a difference in ischaemic risk, especially in contrast to the PLATO trial, which randomised more than 18,000 patients and demonstrated superiority of ticagrelor versus clopidogrel in ACS [3]. Additionally, the study was conducted entirely in South Korea, and there is a high prevalence of CYP2C19 loss-of-function alleles in Koreans; for this reason, this de-escalation strategy should also be evaluated in a more heterogeneous population.

1. 
   
   1. Chang K. A Prospective, Multi-centre, Randomised, Open-label Trial to Compare Efficacy and Safety of Clopidogrel Versus Ticagrelor in Stabilized Patients with Acute Myocardial Infarction After Percutaneous Coronary Intervention. Abstract 407-10, ACC 2021 Scientific Session, 15–17 May.
   2. Rodriguez F, Harrington RA. N Engl J Med 2021 Feb 4;384(5):452–460.
   3. Wallentin L, et al.N Engl J Med 2009;361:1045-1057.

 

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Posted on 9 July, 202122 February, 2024