Tenecteplase (TNK-t-PA) ‏

1. Tenecteplase (TNK-t-PA)‏ Dr WU Kwok Leung PYNEH 28 August 2009

2. Tenecteplase (TNK-t-PA)‏ Genetically engineered, multiple point mutant of tPA Longer plasma half-life -> allow for a single bolus injection 14 times more fibrin specific 80 fold higher resistance to inhibition by plasminogen activator inhibitor 1 (PAI-1) than standard tPA

3. ASSENT-2 Trial Lancet 1999; 354: 716-22 Double-blinded RCT 16949 patients in 1021 hospitals recruited Divided into 2 gps: alteplase infusion or single bolus injection of TNK All patient received aspirin and heparin

4. Inclusion criteria: - > 18yo - onset of Sx < 6 hrs - ECG > 0.1 mV of ST  in 2 or more limb leads or > 0.2 mV in 2 or more contiguous precordial leads

5. Exclusion Criteria - SBP > 180 ; DBP > 110 - Use of GP Iib/IIIa antagonists within preceding 12 hrs - Major surgery within 2m - Head trauma or other trauma after onset of MI - Hx of stroke, TIA or dementia - Known structural damage to CNS - On oral anticoagulation and INR > 1.3 - Sustained CPR (>10 min) in the previous 2 wks - Pregnancy, lactation in previous 30 days

6. Primary Endpoint: - All-cause mortality at 30 days Secondary Endpoint: - Net clinical benefit: absence of death or non-fatal stroke, major non-fatal cardiac events in hospital, and stroke

10. Conclusion TNK and alteplase were equivalent for 30-day mortality Fewer non-cerebral bleeding and fewer blood transfusion in TNK gp Ease of administration of TNK may facilitate early Rx in and out of hospital

11. TNK Rapid reperfusion √ Administration as an iv bolus √ Fibrin specific √ Low incidence of systemic bleeding including ICH ? Resistant to PAI-1 √ Low reocclusion rate No effect on BP √ No antigenicity √

12. Cost • TNK 10x expansive than SK • Due to cost consideration, 1st line Rx was SK in the past • New HA Clinical Practice Guideline (CPG) on management of STEMI was developed

14. TNK – 1st line fibrinolytic New Protocol in Our hospital – Modified from HA CPG

17. Co-therapy: Heparin Improve the rapidity of reperfusion Increase patency rates Reduce risk of reocclusion

18. STEMI: Use of Heparin & Clopidogrel after Fibrinolytic Decision - 1 SK LMWH optional >= 75 < 75 Plavix 300mg as loading, followed by 75mg daily for at least 14 days Plavix 75mg daily for at least 14 days

19. STEMI: Use of Heparin & Clopidogrel after Fibrinolytic Decision - 2 TNK >=75 < 75 30mg enoxaparin iv, followed 15min later by 1mg/kg Q12H sc * for 2-8 days • Omit initial iv bolus of enoxaparin • start enoxaparin 0.75mg/kg Q12H sc* Plavix 300mg as loading, followed by 75mg daily for at least 14 days Plavix 75mg daily for at least 14 days * If estimated Cr clearance < 30ml/min, sc enoxaparin should be given Q24H

20. STEMI: Use of Heparin & Clopidogrel after Fibrinolytic Decision - 3 No fibrinolytic LMWH to be considered < 75 >= 75 Plavix 300mg as loading, followed by 75mg daily for at least 14 days Plavix 75 mg daily for at least 14 days

21. Take Home Message • New protocol on management of STEMI is implemented since 11/7/09 • TNK becomes 1st line fibrinolytic (but remember the exclusion criteria due to the concern of bleeding risk) • Co-therapy with enoxaparin • Issue of plavix

22. THANK YOU!