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Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial
E Magnus Ohman1, Frans Van de Werf, Elliott M Antman
1Division of Cardiology, University of North Carolina, UNC Heart Center, Chapel Hill, NC, USA. mohman@med.unc.edu
Insights
Combining reduced-dose tenecteplase with tirofiban did not improve reperfusion in acute myocardial infarction patients. However, this combination therapy led to faster ST-segment resolution, suggesting enhanced microcirculatory perfusion.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Older fibrinolytic agents combined with glycoprotein IIb/IIIa inhibitors showed modest reperfusion improvements in acute myocardial infarction.
- This study investigated reduced-dose tenecteplase combined with tirofiban.
Purpose of the Study:
- To identify optimal tirofiban doses for enhanced Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow with reduced-dose tenecteplase.
- To assess ST-segment resolution with the combination therapy.
Main Methods:
- A multicenter, dose-ranging study involving 409 patients with myocardial infarction.
- Patients received reduced-dose tenecteplase combined with varying doses of tirofiban or full-dose tenecteplase alone.
- Angiographic assessment of TIMI grade 3 flow and ST-segment resolution at 60 minutes.
Main Results:
- TIMI grade 3 flow at 60 minutes did not significantly differ among dose groups (50%-68%).
- Complete ST-segment resolution was higher in the combination therapy groups compared to tenecteplase alone.
- Major bleeding was infrequent, and no strokes occurred.
Conclusions:
- Combination therapy did not increase reperfusion but achieved similar TIMI flow grades with reduced tenecteplase doses.
- ST-segment resolution was more rapid and complete with combination therapy, indicating potential enhanced microcirculatory perfusion.
- The second stage of the study was not performed due to the initial findings.
Background:
The combination of older reduced-dose fibrinolytic agents and platelet glycoprotein IIb/IIIa inhibitors has shown modest improvements in reperfusion and more striking improvements in ST-segment resolution after acute myocardial infarction. We performed a multicenter dose-ranging study of reduced doses of a newer fibrinolytic (tenecteplase) combined with tirofiban, a glycoprotein IIb/IIIa inhibitor.
Methods:
The first goal of the trial was to identify a dose or doses of tirofiban that, when combined with reduced-dose tenecteplase, would result in a higher incidence of Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow at 60 minutes versus full-dose tenecteplase alone. The second goal was to assess whether the optimum dose(s) from the first stage also would result in greater resolution of ST-segment elevation.
Results:
In all, 409 patients aged 18 to 75 years with myocardial infarction were enrolled. The incidence of TIMI grade 3 flow at 60 minutes did not differ significantly among dose groups, ranging from 50% to 68%. The corrected TIMI frame count likewise did not differ substantially (range 34-42). More patients given combined therapy had complete resolution of ST-segment elevation at 60 minutes compared with patients given tenecteplase alone. Major bleeding was infrequent, and no strokes occurred. Based on angiographic results of the first stage, the second planned stage of the study was not performed.
Conclusions:
Although combination therapies were not associated with increased reperfusion compared with full-dose tenecteplase alone, similar TIMI flow grades were achieved despite reductions in tenecteplase doses. ST-segment resolution was more rapid and complete with combination therapy versus full-dose tenecteplase, suggesting enhanced microcirculatory perfusion to the infarct zone in this dose-ranging trial.
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