TELEX Trial: Ticagrelor vs. Clopidogrel in Acute Coronary Syndrome
The PLATO trial demonstrated that ticagrelor significantly reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke compared to clopidogrel (9.8% vs 11.7%, hazard ratio 0.84) in patients with acute coronary syndrome, without increasing overall major bleeding. 1
Primary Findings
- The primary endpoint (composite of cardiovascular death, myocardial infarction, or stroke) occurred in 9.8% of patients receiving ticagrelor compared with 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 16% reduction seen in the overall trial 2
- Significant reductions were observed in:
Bleeding Outcomes
- No significant difference in overall major bleeding rates between ticagrelor and clopidogrel (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 instances of fatal bleeding of other types were observed with ticagrelor 1
Pharmacodynamic Findings
- Ticagrelor achieved greater platelet inhibition compared to clopidogrel during both loading dose and maintenance therapy phases 3
- 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) 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
Additional Findings
- Dyspnea was more common with ticagrelor than clopidogrel 4
- Ticagrelor does not require hepatic conversion to an active metabolite, allowing for more rapid onset of action compared to clopidogrel 5
- Significant interpatient variability exists in pharmacodynamic response to clopidogrel, which is less pronounced 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 5
- Clopidogrel remains an effective alternative P2Y12 inhibitor for patients with high bleeding risk or contraindications to ticagrelor 2, 6
- For patients requiring CABG surgery, ticagrelor has a shorter recommended interruption period compared to clopidogrel 5
Important Considerations
- Real-world data from a retrospective cohort study showed no significant difference in net adverse clinical events between ticagrelor and clopidogrel at 12 months, but did show higher rates of hemorrhagic events and dyspnea with ticagrelor 7
- In high-risk ACS patients undergoing PCI, ticagrelor significantly reduced in-stent thrombosis and target vessel revascularization compared to clopidogrel 75mg daily, with increased minor bleeding but no difference in major bleeding 8
The PLATO trial established ticagrelor as a more effective antiplatelet agent than clopidogrel for reducing ischemic events in ACS patients, with a mortality benefit and without increasing overall major bleeding risk, though with higher rates of non-procedure-related bleeding and dyspnea.