Unguided de-escalation antiplatelet strategy in stabilized patients with acute myocardial infarction undergoing percutaneous coronary intervention

Key Takeaway

  • In stabilized patients with uncomplicated AMI, an unguided de-escalation DAPT strategy of switching from ticagrelor to clopidogrel met non-inferiority and superiority requirements vs ticagrelor-based continuing standard DAPT, in terms of cardiovascular and bleeding events.
    • The de-escalation strategy was associated with a 45% lower risk of net adverse clinical event for the next 11 months vs ticagrelor-based continuing DAPT strategy.
    • An absolute risk reduction of 3.6% with de-escalation strategy was mainly caused by a significant decrease in bleeding risk

Why This Matters

  • Data on the unguided de-escalation DAPT switching from potent P2Y12 inhibitors to clopidogrel are scarce, but it commonly occurs in clinical practice
  • The TALOS-AMI trial assessed the hypothesis that de-escalation DAPT with clopidogrel might be non-inferior to ticagrelor-based antiplatelet therapy.

Study Design

KEY INCLUSION CRITERIA

  • Patients with biomarker-positive AMI
  • Who underwent successful PCI
  • Tolerated aspirin+ticagrelor treatment at admission
  • Reported no major adverse ischemic or bleeding events during 1 month after AMI

KEY EXCLUSION CRITERIA

  • Patients with cardiogenic shock, active bleeding of any major organs, bleeding diathesis/coagulopathy, gastrointestinal/genitourinary bleeding, and hemoptysis within 2 months

STUDY OUTCOMES

PRIMARY ENDPOINT: Net adverse clinical event* from 1–12 months after index PCI

KEY SECONDARY ENDPOINTS:

  1. Composite of cardiovascular death, MI, and stroke;
  2. Composite of BARC bleeding type 2, 3, or 5;
  3. Composite of cardiovascular death, MI, stroke, and BARC bleeding type 3 or 5 between 1 and 12 months after index PCI

Key Results

Randomization: 2,697 patients assigned† to
(1) De-escalation group (n = 1,349) or
(2) Active control group (n = 1,348)

PRIMARY ENDPOINT (DE-ESCALATION vs ACTIVE CONTROL GROUP)
4.6% vs 8.2% patients
(P non-inferiority <0.001; HR = 0.55, P superiority = 0.0001)
De-escalation group met non-inferiority and superiority requirements vs
active control group
KEY SECONDARY ENDPOINTS (DE-ESCALATION vs ACTIVE CONTROL GROUP)
COMPOSITE OF CARDIOVASCULAR DEATH, MI, AND STROKE 2.1% vs 3.1% patients
(HR = 0.69, P = 0.15)
COMPOSITE OF BARC BLEEDING TYPE 2, 3, OR 5

3.0% vs 5.6% patients
(HR = 0·52, P = 0·0012)
COMPOSITE OF CARDIOVASCULAR DEATH, MI, STROKE, AND BARC BLEEDING 3 OR 5 2.8% vs 4.9% patients
(HR = 0.58, P = 0.0086)

Limitations

  • Open-label and non-placebo-controlled trial
  • Non-inferiority margin seemed to be wide‡§
  • Platelet function test or genotyping was not carried out during the study
  • Inclusion of less severe BARC type 2 bleeding in a net clinical outcome might bias results in favor of de-escalation group
  • De-escalation strategy may not apply to patients with AMI with multivessel disease/complex lesions

* A composite of cardiovascular death, MI, stroke, and bleeding type 2, 3, or 5 according to the BARC criteria.
† At 1 month after index PCI.
‡ HR 1.34.
§ The study should be interpreted with caution, especially in patients at high cardiovascular risk.

ABBREVIATIONS: AMI, acute myocardial infarction; BARC, Bleeding Academic Research Consortium; DAPT, dual anti-platelet therapy; HR, hazard ratio; MI, myocardial infarction; PCI, percutaneous coronary intervention; TALOS-AMI,Ticagrelor versus Clopidogrel in Stabilized Patients with Acute Myocardial Infarction.

    Kim CJ, Park MW, Kim MC, Choo EH, Hwang BH, Lee KY, et al. Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigatorinitiated, open-label, multicentre, non-inferiority, randomised trial. Lancet. 2021;398(10308):1305-1316. doi: 10.1016/S0140- 6736(21)01445-8. PMID: 34627490.

MAT-BH-2300023/v1/Jan2023