Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction - TALOS-AMI

Mar 04, 2024
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC; Kim A. Eagle, MD, MACC
Trial Sponsor:
ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.
Date Presented:
05/16/2021
Date Published:
12/20/2023
Date Updated:
03/04/2024
Original Posted Date:
05/16/2021
References

Contribution To Literature:

Highlighted text has been updated as of March 4, 2024.

The TALOS-AMI trial showed that among patients undergoing PCI for AMI and who had completed 1 month of DAPT with aspirin and ticagrelor uneventfully, switching to aspirin + clopidogrel for the next 11 months met criteria for noninferiority and superiority compared with continuing with aspirin + ticagrelor.

Description:

The goal of the trial was to assess whether de-escalating dual antiplatelet therapy (DAPT) with clopidogrel rather than ticagrelor 1 month after percutaneous coronary intervention (PCI) for an acute myocardial infarction (AMI) would be a noninferior strategy.

Study Design

After successful PCI for AMI, all patients received aspirin + ticagrelor for 30 ± 7 days. Patients without adverse events were randomized to continuing DAPT in a 1:1 open-label fashion with either aspirin + clopidogrel 75 mg daily (de-escalation, n = 1,349) or aspirin + ticagrelor 90 mg BID (n = 1,348). In the de-escalation arm, clopidogrel was administered without a loading dose.

  • Total screened: 2,901
  • Total number of enrollees: 2,697
  • Duration of follow-up: 12 months
  • Mean patient age: 60 years
  • Percentage female: 17%

Inclusion criteria:

  • PCI for AMI
  • No adverse events for 30 days post-PCI

Other salient features/characteristics:

  • Diabetes mellitus: 27%
  • Previous myocardial infarction (MI): 16%
  • Index PCI: non–ST-segment elevation MI (NSTEMI): 46%, STEMI: 54%
  • Infarct-related artery left anterior descending: 49%
  • Multivessel PCI: 27%

Principal Findings:

The primary endpoint of cardiovascular death, MI, stroke, Bleeding Academic Research Consortium (BARC) bleeding 2,3, or 5, for de-escalation vs. active control between 1 and 12 months post-PCI, was: 4.6% vs. 8.2% (p for noninferiority < 0.001, p for superiority < 0.001).

Secondary outcomes:

  • Cardiovascular death, MI, stroke: 2.1% vs. 3.1% (p = 0.15)
  • BARC 2,3, or 5 bleeding: 3% vs. 5.6% (p = 0.001)

High ischemic risk: High ischemic risk was defined as having a history of diabetes or chronic kidney disease, multivessel PCI, ≥3 lesions treated, total stent length >60 mm, ≥3 stents implanted, left main PCI, or bifurcation PCI with ≥2 stents; 50.8% met this definition. De-escalation to clopidogrel, compared with ticagrelor-based DAPT, showed no significant difference in ischemic risk across the high ischemic risk group (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.54-1.45; p = 0.62) and the non–high ischemic risk group (HR, 0.65; 95% CI, 0.33-1.28; p = 0.21), without heterogeneity (p for interaction = 0.47). The bleeding risk of the de-escalation group was consistent in both the high ischemic risk group (HR, 0.64; 95% CI, 0.37-1.11; p = 0.11) and the non–high ischemic risk group (HR, 0.42; 95% CI, 0.24-0.75; p = 0.003), without heterogeneity (p for interaction = 0.32). Findings were consistent across subgroups of clinical profile, procedural factors, and complex PCI.

Interpretation:

The results of this trial indicate that among patients undergoing PCI for AMI and who had completed 1 month of DAPT with aspirin and ticagrelor uneventfully, switching to aspirin + clopidogrel for the next 11 months met criteria for noninferiority and superiority compared with continuing with aspirin + ticagrelor. This was primarily driven by a reduction in major bleeding, but ischemic events were also numerically lower with a de-escalation strategy. De-escalation was performed without genotype testing or reload, and was effective among patients with and without higher ischemic risk. These are interesting data and are likely to be clinically relevant and cost-effective. The only caveat is that this trial only included East Asian patients, so the generalizability in the United States is unclear.

We have seen several interesting trials in the DAPT space in the past few years. Trials such as TWILIGHT have shown that it may be possible to continue ticagrelor monotherapy and drop aspirin after 3 months with no penalty in ischemic outcomes and a reduction in bleeding outcomes among patients undergoing PCI. Similarly, STOPDAPT-2 suggested that clopidogrel monotherapy could be continued after 1 month in patients undergoing PCI for stable ischemic heart disease and ACS. In HOST-REDUCE-POLYTECH-ACS, switching to prasugrel 5 mg daily after 1 month was superior to continuing with prasugrel 10 mg daily.

References:

Lee M, Byun S, Lim S, et al. Dual Antiplatelet Therapy De-Escalation in Stabilized Myocardial Infarction With High Ischemic Risk: Post Hoc Analysis of the TALOS-AMI Randomized Clinical Trial. JAMA Cardiol 2024;9:125-33.

Kim CJ, Park MW, Kim MC, et al; TALOS-AMI Investigators. Unguided de-escalation from ticagrelor to clopidogrel in stabilized patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicenter, non-inferiority, randomized trial. Lancet 2021;398:1305-16.

Presented by Dr. Kiyuk Chang at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 16, 2021.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS

Keywords: ACC21, Acute Coronary Syndrome, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors


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