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

TELEX Trial Summary: Ticagrelor vs Clopidogrel in Acute Coronary Syndrome

The TELEX trial demonstrated that ticagrelor significantly reduced the primary composite endpoint of cardiovascular death, myocardial infarction, and stroke by 16% compared to clopidogrel in patients with acute coronary syndrome, without increasing overall major bleeding rates. 1

Primary Findings

• The primary composite endpoint (cardiovascular death, 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 between ticagrelor and clopidogrel groups (11.6% vs 11.2%, p=0.43) 1
• Ticagrelor was associated with higher rates of non-CABG-related major bleeding (4.5% vs 3.8%, p=0.03) 1
• More instances of fatal intracranial bleeding but fewer fatal bleeding events of other types were observed with ticagrelor 1

Invasive Strategy Subgroup

• For the 72% of patients (13,408 of 18,624) with a planned invasive strategy, the primary endpoint occurred in 9.0% of ticagrelor patients vs 10.7% of clopidogrel patients (HR 0.84,95% CI 0.75-0.94, p=0.0025) 4
• No difference in total major bleeding (11.6% vs 11.5%, p=0.8803) or severe bleeding (3.2% vs 2.9%, p=0.3785) in the invasive strategy subgroup 4

Pharmacological Advantages of Ticagrelor

• Ticagrelor does not require hepatic conversion to an active metabolite, allowing for more rapid onset of action compared to clopidogrel 2, 3, 5
• Ticagrelor achieves inhibition of platelet aggregation within 30 minutes, exceeding that obtained with loading doses of clopidogrel 5
• Significant interpatient variability exists in pharmacodynamic response to clopidogrel, which is less pronounced with ticagrelor 2, 3
• Platelet function studies demonstrated greater suppression of platelet reactivity with ticagrelor compared to clopidogrel 6

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 compared to clopidogrel 2, 3
• 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, which is an important consideration for patient selection 2, 5

Important Considerations

• Ticagrelor is administered as a 180 mg loading dose followed by 90 mg twice daily, while clopidogrel is given as a 300-600 mg loading dose followed by 75 mg daily 1
• Proton pump inhibitor use was associated with higher platelet reactivity with clopidogrel but not with ticagrelor 6
• Low-dose ticagrelor has also shown promising results in reducing major adverse cardiac events compared to standard-dose clopidogrel without increasing bleeding risk, though this was not part of the main TELEX trial 7