What are the results of trials on TNKase (Tenecteplase) in STEMI (ST-Elevation Myocardial Infarction)?

From the Guidelines

TNKase (Tenecteplase) in STEMI (ST-Elevation Myocardial Infarction) trials show mixed results, but overall, tenecteplase-facilitated percutaneous coronary intervention (PCI) does not demonstrate a significant benefit over primary PCI.

Key Findings

• The ASSENT-4 PCI trial 1 found that full-dose tenecteplase and PCI had a higher in-hospital mortality rate compared to primary PCI.
• The WEST trial 1 showed a trend toward a reduction in the 30-day composite end point of death or reinfarction with PCI after tenecteplase compared to tenecteplase alone, but this was not statistically significant.
• The CAPITAL AMI trial 1 found that routine immediate PCI after tenecteplase reduced the primary composite end point of death, reinfarction, recurrent unstable ischemia, or stroke at 6 months.
• A pooled analysis of 7 published trials 1 found a significant 38% reduction in mortality and a 41% reduction in reinfarction with immediate or early stenting after fibrinolysis compared to ischemia-guided or routine delayed stenting.

Treatment Strategy

• The combination of tenecteplase, enoxaparin, aspirin, and clopidogrel is a widely studied and validated pharmaco-invasive strategy for STEMI patients 1.
• Tenecteplase is administered as a single weight-adjusted intravenous bolus, making it convenient for pre-hospital use.
• The dose of tenecteplase should be reduced by 50% in elderly patients (>75 years) to minimize the risk of stroke 1.

Clinical Implications

• Facilitated PCI using regimens other than full-dose fibrinolytic therapy may be considered as a reperfusion strategy in high-risk patients when PCI is not immediately available and bleeding risk is low 1.
• However, a planned reperfusion strategy using full-dose fibrinolytic therapy followed by immediate PCI may be harmful 1.

From the FDA Drug Label

TNKase is a tissue plasminogen activator, indicated to reduce the risk of death associated with acute ST elevation myocardial infarction (STEMI). Initiate treatment as soon as possible after the onset of STEMI symptoms. Increased Risk of Heart Failure and Recurrent Ischemia when used with Planned Percutaneous Coronary Intervention (PCI) in STEMI: In patients with a large ST segment elevation myocardial infarction, physicians should choose either thrombolysis or PCI as the primary treatment strategy for reperfusion

The results of trials on TNKase (Tenecteplase) in STEMI (ST-Elevation Myocardial Infarction) are not explicitly stated in the provided drug label. However, it is indicated that TNKase is used to reduce the risk of death associated with acute STEMI.

• Key Points:
  • TNKase is indicated for STEMI
  • Treatment should be initiated as soon as possible after STEMI symptoms
  • There is an increased risk of heart failure and recurrent ischemia when used with planned PCI in STEMI 2

From the Research

Efficacy of TNKase (Tenecteplase) in STEMI

• The STREAM-2 study 3 aims to compare the efficacy and safety of a novel pharmaco-invasive strategy using half-dose tenecteplase with routine primary percutaneous coronary intervention (PCI) in STEMI patients ≥60 years.
• A network meta-analysis 4 found that tenecteplase tended to be associated with lower risk of bleeding compared with other fibrinolytic regimens.
• The INTEGRITI Phase II Angiographic Trial 5 found that double-bolus eptifibatide plus half-dose tenecteplase tended to improve angiographic flow and ST-segment resolution compared with tenecteplase monotherapy.
• The Elaxim Indian Registry 6 reported a clinically successful thrombolysis rate of 90.93% with single intravenous bolus administration of tenecteplase in 6000 patients with STEMI.

Safety of TNKase (Tenecteplase) in STEMI

• The STREAM-2 study 3 will assess key safety criteria, including total stroke, intracranial hemorrhage, and major non-intracranial bleeds.
• The network meta-analysis 4 found that the addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding.
• The INTEGRITI Phase II Angiographic Trial 5 found that double-bolus eptifibatide plus half-dose tenecteplase was associated with more major hemorrhage and transfusions compared with tenecteplase monotherapy.
• The Elaxim Indian Registry 6 reported an overall incidence of intracranial hemorrhage of 0.62% and severe bleeding of 3.18% with tenecteplase.

Comparison with Other Treatments

• The EuroIntervention study 7 compared intracoronary tenecteplase with abciximab as adjunctive treatment during primary PCI in patients with anterior myocardial infarction, and found that tenecteplase did not reduce infarct size compared with abciximab.
• The network meta-analysis 4 found that tenecteplase, alteplase, and reteplase had similar efficacy and safety profiles, while streptokinase and non-accelerated infusion of alteplase were associated with increased risk of all-cause mortality.