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: Secondary Endpoint: - All-cause mortality at 30 days
- 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 - 1SK
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!