Unguided de-escalation from Ticagrelor to Clopidogrel

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.

MAT-BH-2300023/v1/Jan2023