TELEX Trial: Ticagrelor vs Clopidogrel in Acute Coronary Syndrome
The PLATO (PLATelet inhibition and patient Outcomes) trial, also known as TELEX, demonstrated that ticagrelor significantly reduced the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke compared to clopidogrel (9.8% vs 11.7%, hazard ratio 0.84) in patients with acute coronary syndrome, with a notable reduction in all-cause mortality without increasing overall major bleeding risk. 1, 2
Primary Findings
- Ticagrelor reduced the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke by 16% compared to clopidogrel (9.8% vs 11.7%, HR 0.84,95% CI 0.77-0.92, p<0.001) 1
- All-cause mortality was significantly reduced with ticagrelor (4.5% vs 5.9%, p<0.001) 1
- Cardiovascular death was reduced with ticagrelor (4.0% vs 5.1%, p=0.001) 1
- Myocardial infarction rates were lower with ticagrelor (5.8% vs 6.9%, p=0.005) 1
- No significant difference was found in stroke rates (1.5% vs 1.3%, p=0.22) 1
Bleeding Outcomes
- Overall major bleeding rates were similar between ticagrelor and clopidogrel groups (11.6% vs 11.2%, p=0.43) 1
- Non-CABG related major bleeding was higher with ticagrelor (4.5% vs 3.8%, p=0.03) 1
- Ticagrelor was associated with more fatal intracranial bleeding but fewer fatal bleeding events of other types 1
Mechanism of Action and Pharmacodynamics
- Ticagrelor is a direct-acting, reversible P2Y12 receptor inhibitor with more rapid onset and more pronounced platelet inhibition than clopidogrel 1, 3
- During maintenance therapy, ticagrelor achieved greater suppression of platelet reactivity compared to clopidogrel (mean maximum light transmittance aggregometry responses to ADP 20 μM: 28±10% for ticagrelor vs 44±15% for clopidogrel, p<0.001) 3
- High platelet reactivity was observed more frequently in the clopidogrel group 3
- Proton pump inhibitor use was associated with higher platelet reactivity with clopidogrel but not with ticagrelor 3
Subgroup Analyses
- In patients with a planned invasive strategy (72% of total participants), ticagrelor showed consistent benefits with a primary endpoint rate of 9.0% vs 10.7% for clopidogrel (HR 0.84,95% CI 0.75-0.94, p=0.0025) 2
- Among patients managed without a planned invasive strategy (28% of participants), ticagrelor showed a 15% reduction in the primary endpoint, consistent with the overall trial results 4
- Low-dose ticagrelor has also been studied and shown to significantly reduce major adverse cardiac events compared to standard-dose clopidogrel (OR 0.39,95% CI 0.26-0.58, p<0.01) without increasing major bleeding events 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 4
- For patients requiring CABG surgery, ticagrelor has a shorter recommended interruption period (3-5 days) compared to clopidogrel (5 days) 4
- Clopidogrel remains an effective alternative P2Y12 inhibitor for patients with high bleeding risk or contraindications to ticagrelor 4
- Significant interpatient variability exists in pharmacodynamic response to clopidogrel, which is not seen to the same extent with ticagrelor 4, 3
Practical Considerations
- Ticagrelor requires twice-daily dosing (90 mg BID) compared to once-daily dosing for clopidogrel (75 mg daily) 1
- Dyspnea occurs in up to 15% of patients taking ticagrelor 6
- Ticagrelor does not require hepatic conversion to an active metabolite, allowing for more rapid onset of action compared to clopidogrel 6
- In patients undergoing PCI, ticagrelor significantly reduced the rate of in-stent thrombosis compared to clopidogrel 75 mg daily 7
The PLATO/TELEX trial established ticagrelor as a superior antiplatelet agent to clopidogrel for reducing cardiovascular events and mortality in ACS patients, though with a slightly increased risk of non-procedure-related bleeding.