Fibrinolytic therapy became the first effective treatment to reduce morbidity and Mortality in ST Elevation myocardial infarction (STEMI) for which American Heart Association/ American College of Cardiology has laid down clear-cut guidelines regarding the eligibility of patients. Though accessible to virtually all patients, fibrinolysis fails to reopen occluded arteries in > 50% of cases.

           

Numerous papers have compared and established the superiority of reperfusion by percutaneous coronary intervention (PCI) in STEMI as it reduces death rate regardless of time from onset of symptom.

           

Introduction of streptokinase (SK) a first generation thrombolytic was a major mile store in the management of ST Elevation Myocardial infarction (STEMI) which conclusively improved outcome in patients. Despite its initial conflicting results, the GISSI Trail in 1986 validated SK as an effective therapy and established a fixed  protocol for its use in STEMI. However, SK has its certain drawbacks like less fibrin selectivity, antigenicity, prolonged time of administration and increased risk of bleeding, thus the search for better option leading to the development of second & third generation thrombolytic. Alteplase, a second generation thrombolytic was similar to the endogenous tissue plasminogen activator (tPA), showing superiority to SK in terms of improved patient outcome, high fibrin specificity and non- antigenicity. However, Alteplase is administered over 90 minutes (occluded inferior)  and is susceptible to the endogenous plasminogen activator inhibitor-1 (PAI-1). The third generation thrombolytic tenecteplase (TNK) is a bio engineered genetically modified version of motive alteplase long half life, greater resistance to inhibitors by PAI-1 increased & fibrin specificity have planned clearance rate & given as a single bolus  over 5 seconds. Due to its higher fibrim specificity  it improves clot lysis &  decreases systemic fibrinolysis thus further reducing incidence of systemic bleeding.

This is compatibles for dcombination with a board range of other antiplated drugs like glycoprotein (GP) IIb/IIIa, low molecular weight heparins. Unfractinated heparin aspirin while earlier thrombolytic alteplase & reieplase may precipitate & administration of heparins.                                     

The extent of thrombolytic usage in India can be understood to some degree through the CREATE study8. Out of 12,405 STEMI patients, only 58.5% received any thrombolytic and only 8% received PCI. There is a dire need for making available reperfusion options to 100% patients. This involves availability of more equipped ambulances, better trained paramedics, wide-spread availability of thrombolytics and more PCI centers. Patient education to avoid delays in consulting doctors is also of paramount importance.

           

In this issue of the Indian Heart Journal, Iyengar et al., present the Indian clinical experience on use of tenecteplase in 2100 patients of STEMI. It is very gratifying to note that more than 90% patients received anti-platelets and heparins. Thrombolysis was seen in 86.71% with an in-hospital mortality was 3.48%. The adverse events recorded were at par with previously published data. Any bleeding (excluding intra-cranial hemorrhage was seen in 4.62% patients. Intra-cranial hemorrhage was reported in 0.90% patients of which 47.34% patients had also received GpIIb/IIIa inhibitors. The best results were seen in patients who received tenecteplase within 3 hours with 89.14% reperfusion. Earlier studies have shown that the indigenously developed tenecteplase achieved TIMI 2/3 flow in approximately 80% patients.

           

In future, the way forward would be to use tenecteplase for pre-hospital thrombolysis and thus help increase myocardial salvage. It is also important to conduct pharmaco-economic studies to delineate the long-term financial impact of morbidity due to use of earlier generation thrombolytics and even delayed angioplasty and thus rightly assess the cost-effectiveness of recent thrombolytics like tenecteplase.

SUMMARY
The introduction of the indigenously developed tenecteplase is a turning point in the management of STEMI in India. It is heartening to note that clinicians are rapidly sharing their clinical experiences of using tenecteplase through this Journal and the CSI conferences. Such public domain information will no doubt increase the awareness and urgent actions in the management of STEMI with the best available reperfusion strategy. Depending on resources, each district and state needs to define those treatment strategies that should be a judicious use of pharmacological and mechanical reperfusion. In the field of pharmacological reperfusion, the best available thrombolytic, like tenecteplase, should always be used not only for immediate results but also to avoid long term consequences of inadequate thrombolysis using older drugs. In the area of mechanical reperfusion, increased infrastructure and more expert manpower is definitely called for. The best management of STEMI can happen only from a concerted effort by all stakeholders – the doctors (primary physicians, cardiologists, and interventionalists), the pharmaceutical industry, the government and definitely the patients and their relatives.

REFERENCES
1. The Task Force on the management of ST-segment elevation acute myocardial infarction of European Society of Cardiology. Eur Heart J, 2008, 29, 2909-2945.
2. Antman EM, Hnad M, Armstrong PW et al. 2007 FocusedSupdateFof theSACC/AHAT2004 guidelines for the management of patients with ST-elevation myocardial infarction. Circulation 2008;117;296-329
3. Boden WE, Eagle K, Granger CB. J Am Coll Card,. 2007, 50, 10, 917-929.
4. Hermentin P, Cuesta-Linker T, Weisse J et al. Comparative analysis of the activity and content of different streptokinase preparations. Eur. Heart J., 2005; 26: 933 - 940.
5. Alexander T, Krishnaswami S, Khanduri U. Anti-streptokinase levels in Indian patients. Int J Cardiol. 1991 Sep;32(3):361-4.
6. ASSENT 2 Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: The ASSENT 2 double blind randomised trial. Lancet 1999;354:716–722.
7. Edmond JJ, Juergens CP, French JK. The pharmaco-invasive approach to STEMI: when should fibrinolytic-treated patients go to the ‘‘cath lab’’? Heart 2009;95;358-361
8. Xavier D , Pais P, Devereaux PJ et. al. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet 2008, 371, 1435-1442.