Tenecteplase: Superior Thrombolytic.pptx

A fibrin-specific agent should be preferred. Single-bolus weight adjusted Tenecteplase tissue plasminogen activator (TNK-tPA) is equivalent to accelerated tPA in reducing 30day mortality, but is safer in preventing non-cerebral bleeds and blood transfusion, and is easier to use in the pre-hospital setting.

1. WELCOME

2. Overview of AMI/Heart Attack

3. Heart muscle needs oxygen to survive. A heart attack/MI occurs when the blood flow that brings oxygen to the heart muscle is severely reduced or cut off completely. This happens because coronary arteries that supply the heart muscle with blood flow can become narrowed from a buildup of fat, cholesterol and other substances that together are called plaque. This slow process is known as atherosclerosis . Heart attack/MI

4. When plaque within a heart artery breaks, a blood clot forms around the plaque. This blood clot can block the blood flow through the artery to the heart muscle. Ischemia results when the heart muscle is starved for oxygen and nutrients. When damage or death of part of the heart muscle occurs as a result of ischemia, it’s called a heart attack, or myocardial infarction (MI). Heart attack/MI (Cont.)

5. Acute myocardial infarction (AMI): facts 1. Thygesen et al. J Am Coll Cardiol 2012;60:1581-1598. 2. WHO Global Atlas on CV Disease, 2011. 3. Roger et al. Circulation 2012;125:e2-e220. AMI is a leading cause of death worldwide 1 Approximately 42% of all deaths from cardiovascular disease are due to AMI 2 Men have a higher risk than women for AMI 3 Risk of AMI increases with advancing age for both genders 3 Black men & women are more at risk than white men & women 3 Incidence is increasing in developing and transitional countries, partly due to increasing longevity, urbanisation and lifestyle changes 3

6. STEMI: A common name for ST-elevation myocardial infarction, a type of heart attack caused by a complete blockage in a coronary artery. NSTEMI: A non-ST-elevated myocardial infarction, a type of heart attack in which an artery is partially blocked and severely reduces blood flow. Types of Heart attack/MI

7. CHEST DISCOMFORT Most heart attacks involve discomfort in the center of the chest that lasts more than a few minutes, or that goes away and comes back. It can feel like uncomfortable pressure, squeezing, fullness or pain. DISCOMFORT IN OTHER AREAS OF THE UPPER BODY Symptoms can include pain or discomfort in one or both arms, the back, neck, jaw or stomach. SHORTNESS OF BREATH with or without chest discomfort. OTHER SIGNS may include breaking out in a cold sweat, nausea or lightheadedness. Symptoms of Heart attack/MI

8. ST-segment elevation with pathological Q-wave formation Sometimes T-wave inversion may be found but it is a non-specific feature ST-segment elevation indicates full thickness cardiac muscle injury, pathological Q-wave indicates muscle necrosis and T-wave inversion indicates muscle ischaemia 8 Diagnosis of STEMI: ECG changes Normal ECG STEMI NSTEMI NSTEMI T-wave inversion ST depression PR Interval QT Interval P Q S T R PR Segment QRS Segment ST Segment P Q S R PR Segment QRS Segment ST Segment P Q S T R PR Segment QRS Segment P Q R PR Segment QRS Segment ST Elevation

9. Atherosclerosis - Circulatory System and Disease - NCLEX-RN - Khan Academy.mp4

10. Cell death does not occur immediately At 30-40 min, irreversible cell death of the myocardium begins and function is disrupted. After approximately 6-8 min, necrosis of the ischaemic myocardium sets in Thrombolytic treatment, starting 1 hour after onset, salvages 70% of the jeopardised myocardium, but starting 5 hours after onset no myocardium can be salvaged. Early reperfusion is essential to prevent loss of myocardial function.

11. The current recommended time-to-treatment system goals acknowledge a critical total ischemic time of 120 minutes and an ideal "golden hour" of 60 minutes the first hour = the ‘golden hour’ Medscape www.stemi-care.com/metalyse

12. Diagnosis of myocardial infarction

13. Treatment Re-establish myocardial reperfusion before irreversible damage occurs: Mechanically (percutaneous coronary intervention) Pharmacoinvasive Strategy Pharmacologically

14. Rationale for pre-hospital thrombolysis (PHT) and pharmaco-invasive strategy Not all medical centres are PPCI-capable 1,2 &/or pre-hospital delays often prevent patients from receiving timely PPCI 3,4 No specialist equipment required and PHT has been established as a safe and effective treatment for STEMI 5 PHT reduces time to reperfusion and improves outcomes if PPCI is not possible within 2h 6,7 Steg et al. Eur Heart J 2012;33:2569-2619. Pinto et al. Circulation 2006;114:2019-2025. Armstrong, Bowden. Ann Intern Med 2011;155:389-391. Armstrong et al. N Engl J Med 2013;368(15):1379-1387. O’Gara et al. J Am Coll Cardiol 2013;61:e78-e140. Morrison et al. JAMA 2000;283(20):2686–2692. Wallentin et al. Circulation 2003;108:135-142. Gershlick et al. N Engl J Med 2005;353:2758-2768. Pharmaco -invasive strategy may achieve reperfusion directly; in case of thrombolysis failure, reperfusion can be achieved with subsequent rescue PCI 8

15. Thrombolytic agents The thrombolytic agents available today are serine proteases that work by converting plasminogen to the natural fibrinolytic agent plasmin. Plasmin lyses clots by breaking down the fibrinogen and fibrin contained in a clot. Tissue plasminogen activator ( tPA ) is a naturally occurring fibrinolytic agent found in vascular endothelial cells and is involved in the balance between thrombolysis and thrombogenesis . It exhibits significant fibrin specificity and affinity. At the site of the thrombus, the binding of tPA and plasminogen to the fibrin surface induces a conformational change that facilitates the conversion of plasminogen to plasmin and dissolves the clot.

16. Fibrinolytic agents, sometimes referred to as plasminogen activators, are divided into the following two categories: Fibrin-specific agents Non–fibrin-specific agents Types of thrombolytic agents

17. Evolution of thrombolytics (International Journal of Bio-Science and Bio-Technology, March 2011;3(1):1-17)

18. Limitations of Streptokinase A higher rate of stroke and intracerebral hemorrhaging is seen Streptokinase is associated with allergic reactions, within 4 days antibodys are found. At least one year break should be made between two prescriptions. Continuous infusion

19. Mehta, Textbook of STEMI Interventions Comparative study among all Fibrinolytics

20. ESC STEMI guidelines 2017: reperfusion strategies Time to PCI centre STEMI diagnosis (ECG) 24h Time from diagnosis ≤2 h >2h Adapted from ESC Task Force. Eur Heart J 2018; 39(2):119–177 . 10 min 90 min 2 h Primary PCI Pharmacoinvasive strategy* Bolus fibrinolytic Transfer to PCI centre Reperfusion successful? No Rescue PCI Routine PCI Yes 60-90 min ≥120 min Alert & immediate transfer to PCI centre *If fibrinolysis is contraindicated, transfer to PCI centre regardless of time to PCI max. 10 min delay to administration

21. Tenecteplase Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modification at three sites of the protein structure.

22. Molecular modifications in the tenecteplase molecule compared to alteplase

23. Mode of action PLAGMINOGEN PLASMIN FIBRIN FIBRIN DEGRADATION PRODUCTS Tissue Plasminogen activator ( tPA )

24. Indication Acute Myocardial Infarction (AMI) Acute Ischemic Stroke (AIS)

25. Dosage & Administration Tenecteplase should be administered on the basis of body weight, with a maximum dose of 50 mg tenecteplase . The required dose should be administered as a single intravenous bolus over 5 to 10 seconds.

26. Reconstitution method Withdraw 10 mL of Sterile Water for Injection (SWFI), Inject the entire contents of the syringe (10 mL) into the TPlase vial directing the diluent stream into the powder. Slight foaming upon reconstitution is not unusual ; any large bubbles will dissipate if the product is allowed to stand undisturbed for several minutes. Gently swirl until contents are completely dissolved. DO NOT SHAKE. The reconstituted preparation results in a colorless to pale yellow transparent solution. Determine the appropriate dose of Tplase and withdraw this volume ( in milliliters) from the reconstituted vial with the syringe. Any unused solution should be discarded. Once the appropriate dose of Tplase is drawn into the syringe, stand the shield vertically on a flat surface 

27. Contraindications Active internal bleeding; history of cerebrovascular accident; intracranial or intraspinal surgery, or trauma within 2 months; intracranial neoplasm, arteriovenous malformation, or aneurysm; known bleeding diathesis; and severe uncontrolled hypertension.

28. Drug interactions Drugs that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after Tenecteplase therapy

29. Special populations Pediatric Use The safety and effectiveness of Tplase in pediatric patients have not been established. Geriatric Use In elderly patients, the benefits of Tplase on mortality should be carefully weighed against the risk of increased adverse events, including bleeding.

30. Pregnancy & Lactation The benefit of treatment must be evaluated against the potential risks in case of myocardial infarction during pregnancy. It is not known if tenecteplase is excreted into breast milk.

31. Distinct Features The only lytic delivered as a 5-second IV bolus for the treatment of AMI Increased Fibrin Specificity Greater Resistance to Plasminogen Activator Inhibitor-1 Long Plasma Half-Life

32. Both ESC & AHA recommend tenecteplase for the management of STEMI patients When fibrinolysis is the reperfusion strategy, it is recommended to initiate this treatment as soon as possible after STEMI diagnosis, preferably in the pre-hospital setting When inter-hospital transport times are short, there may be advantages to the immediate delivery of fibrinolytic therapy versus any delay to primary PCI for patients with STEMI and low bleeding risk who present within the first 1 to 2 hours of symptom onset Ref. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, page-e 95 & 2017 ESC Guidelines for themanagement of acutemyocardial infarction in patients presenting with ST-segment elevation, page 139

33. Thank you !