What were the results of the TELEX (Ticagrelor (ticagrelor) vs clopidogrel (clopidogrel)) trial in patients with acute coronary syndrome?

TELEX Trial Results: Ticagrelor vs Clopidogrel in Acute Coronary Syndrome

Ticagrelor demonstrated a 16% reduction in the composite endpoint of cardiovascular death, myocardial infarction, and stroke compared to clopidogrel in patients with acute coronary syndrome, with a significant reduction in cardiovascular mortality but an increased risk of non-procedure-related bleeding. 1

Primary Findings

• The PLATO (PLATelet inhibition and patient Outcomes) trial, also known as TELEX, was a multicenter, double-blind, randomized trial comparing ticagrelor (180-mg loading dose, 90 mg twice daily) with clopidogrel (300-600-mg loading dose, 75 mg daily) in 18,624 patients with acute coronary syndrome 1
• At 12 months, the primary composite endpoint (death from vascular causes, myocardial infarction, or stroke) occurred in 9.8% of patients receiving ticagrelor compared to 11.7% of those receiving clopidogrel (hazard ratio 0.84; 95% CI, 0.77-0.92; p<0.001) 1
• Ticagrelor showed a consistent 15% reduction in the primary endpoint among patients managed without a planned invasive strategy, aligning with the overall trial results 2, 3
• Significant reductions were observed in:
  • Myocardial infarction (5.8% vs 6.9%, p=0.005) 1
  • Death from vascular causes (4.0% vs 5.1%, p=0.001) 1
  • All-cause mortality (4.5% vs 5.9%, p<0.001) 1

Bleeding Outcomes

• No significant difference in overall major bleeding rates was found between ticagrelor and clopidogrel groups (11.6% vs 11.2%, p=0.43) 1
• Ticagrelor was associated with a higher rate of non-procedure-related major bleeding (4.5% vs 3.8%, p=0.03) 1
• More instances of fatal intracranial bleeding but fewer instances of fatal bleeding of other types were observed with ticagrelor 1
• Minor bleeding was significantly increased with ticagrelor compared to clopidogrel 75mg during hospitalization (45.5% vs 26.2%, p=0.012) and at 6-month follow-up (66.9% vs 45.9%, p=0.004) 4

Pharmacodynamic Advantages of Ticagrelor

• Ticagrelor achieves greater suppression of platelet reactivity compared to clopidogrel during maintenance therapy 5
• Mean maximum light transmittance aggregometry responses (adenosine diphosphate 20 μM) post-maintenance dose were 44±15% for clopidogrel and 28±10% for ticagrelor (p<0.001) 5
• Ticagrelor does not require hepatic conversion to an active metabolite, allowing for more rapid onset of action compared to clopidogrel 2, 3, 6
• High platelet reactivity was observed more frequently in patients receiving clopidogrel 5
• Proton pump inhibitor use was associated with higher platelet reactivity with clopidogrel but not with ticagrelor 5

Clinical Implications

• The American College of Cardiology/American Heart Association guidelines recommend ticagrelor over clopidogrel for ACS patients due to its superior reduction in cardiovascular events 2, 3
• For patients requiring CABG surgery, ticagrelor has a shorter recommended interruption period (5 days) compared to clopidogrel 2, 3, 6
• Clopidogrel remains an effective alternative P2Y12 inhibitor for patients with high bleeding risk or contraindications to ticagrelor 2, 3
• Dyspnea occurs in up to 15% of patients taking ticagrelor, representing a notable side effect 2, 6
• In-stent thrombosis and target vessel revascularization rates were significantly reduced with ticagrelor compared to clopidogrel 75mg daily 4

Invasive Strategy Subgroup

• In the 13,408 patients (72.0% of total) for whom an invasive strategy was planned, the primary composite endpoint occurred in fewer patients in the ticagrelor group (9.0%) than in the clopidogrel group (10.7%), with a hazard ratio of 0.84 (95% CI, 0.75-0.94; p=0.0025) 7
• This benefit was consistent with the overall trial results, suggesting ticagrelor's superiority regardless of management strategy 7