Introduction:
Tenecteplase is a third generation, fibrin-specific, single-bolus intravenous fibrinolytic drug. Indigenous Tenecteplase has been available in India since 2007. The earliest data with this Tenecteplase was presented at the CSI conference in 2008 at Chennai on 48 Indian patients with STEMI, in which pain relief occurred in 91%, the reperfusion rate (>50% ST resolution at 90-min) was 88%, and peak of CKMB rise in 12-hours was seen in 86%1. Following this, a larger study by Sathyamurthy et al. was published in 2008, where in 507 patients with STEMI who received treatment with weight-adjusted Tenecteplase, 85.99% had resolution of chest pain, with median duration required for ≥50% resolution of ST segment of 75-minutes. Incidence of intra-cranial hemorrhage (ICH) was 0.39%, re-infarction was 2.96% and death was 2.36%2. The aim of this article is to present a brief overview of the efficacy and safety of indigenous Tenecteplase used in Indian STEMI patients in clinical practice.

Materials and Methods:
This is a post-licensure, observational, prescription event monitoring (PEM) study allowed by the DCGI (on 21.10.2008) as part of post-marketing surveillance for regulatory compliance. For this, the Elaxim Indian Registry data from the de-identified case record forms of 2100 patients (as of September 20, 2009) received from 414 cardiologists/physicians from 248 centers in India was analyzed. All the patients had received in-hospital Tenecteplase (Elaxim Injection, manufactured by Gennova Biopharmaceuticals Limited, Pune) as part of their clinical management at the sole decision of the attending Physician, after taking care of precautions and contraindications. Weight-adjusted dosing of Tenecteplase was followed as per prescribing information. The adjunctive therapy and standard of care was as practiced by the respective care provider. The authors were responsible for reviewing and analyzing the data.

           

Results:
Of the 2100 patients, 16.62% were females. The overall mean age was 56.98 (± 12.11) years and mean weight was 69.37 (± 10.81) kg. There were 51.14% hypertensives, 40.14% diabetics, 30.19% hyperlipidemic and 30.86% patients were smokers. History of prior known ischemic heart disease was obtained from 18.76% patients.

           

Almost all patients received aspirin (98.62%) and clopidogrel (98.43%). Heparin (UFH/enoxaparin), beta-blockers and nitroglycerine were received by 90.29%, 39.90% and 44.95% patients respectively. GpIIb/IIIa inhibitors were administered in 9.67% patients. Reasons for administration of GpIIb/IIIa inhibitors were at the discretion of the attending physician; in 35.96% patients angioplasty was done soon after, in 1.38% patients it was given after reinfarction and in the rest 49.75% patients there were no obvious reason for administering GpIIb/IIIa inhibitors .The median time to administration of tenecteplase after chest pain onset was 120 min (1st quartile = 60 min, 3rd quartile = 180 min.). Proportion of patients who were treated within 3 hours, 3-6 hours and after 6 hours was 64.42%, 29.00% and 6.57% respectively.The efficacy and safety data is presented in Table 1 and Table 2 respectively. The data reported an incidence of 11.33% PTCA, 9.19% received stents, 4.33% underwent CABG, and overall 26.81% had undergone angiography before discharge.

Table 1. Efficacy of Indigenous Tenecteplase in Indian STEMI patients.
Parameter	Overall	Treated at <3 hrs*	Treated at 3-6 hrs*	Treated at >6hrs*
Chest pain resolution	91.90%	93.94%	91.63%	79.10%
Median time for chest pain resolution (min.)	45	45	60	60
Median time for >50% ST resolution (min.)	85	60	90	105

Thrombolysis considered clinically successful	86.71%	89.14%	85.06%	73.88%
* after onset of chest pain

 

 

The other limitation in this study is the absence of post-thrombolytic angiographic data. The data from Apollo Hospitals show a TIMI 2/3 flow rate of 80% (personal communication, Dr I S Sathyamurthy); in a series at Ruby Hall Clinic Pune the TIMI 2/3 was seen in 90% patients (personal communication, Dr P K Grant) and in the pre-licensing data with the manufacturer, the TIMI 2/3 was seen in 85.1% patients (n=47). The ACC/AHA guideline provides a figure of 83% TIMI 2/3 with Tenecteplase based on published studies4. Many factors should be acknowledged as contributing to the success of any thrombolytic therapy; in this study it was heartening to note about two-thirds of patients could be treated within 3 hours, and that aspirin, clopidogrel and heparin/enoxaparin was used in over 90% patients.

This study suggests that, although primary PCI has been considered to be the gold standard, there is enough scope of appropriate use of a thrombolytic which does not require extensive infrastructure or intensive manpower. Early use of a thrombolytic can always be followed up later with angiography and angioplasty (if required) without adding to the immediate stress of transferring an unstable patient and having to arrange larger finances. Apart form availability, the key issue in early use of a thrombolytic is the door-to-needle time, and the ability to administer the drug without losing any time in infusions within the golden hour. In this regard, Tenecteplase being a single intravenous bolus injection offers the best alternative to products like streptokinase (allergenic, long infusion time), reteplase (two bolus doses, less fibrin specific, no weight adjusted dosing) or urokinase (long infusion time, not approved by US FDA for STEMI). This, coupled with the high efficacy and safety, makes Tenecteplase the fibrinolytic agent of choice in current practice. Future studies should explore the improvement in fibrinolysis when this agent is administered in a pre-hospital setting in the Indian context.

Conclusion:

The indigenously developed Tenecteplase shows high efficacy and safety in its in-hospital use and this is a definite improvement in and a welcome addition to the Physician’s armamentarium in the management of STEMI. The advantages of Tenecteplase should be further utilized and studied in the pre-hospital administration setting.

References:

1) KN Srinivasan, I Sathyamurthy, K Jayanthi, D Vaidhiyanathan, D Prabhakar, P Ramachandran, K Subramanyan Tenecteplase in STEMI: Indian Experience. Abstract 133. Indian Heart J 2008; 60(5): 386 – 420.

2) I Sathyamurthy, KN Srinivasan, K Jayanthi, D Vaidiyanathan, D Prabhakar, P Ramachandran. Efficacy and Safety of Tenecteplase in Indian Patients with ST-segment Elevation Myocardial Infarction. Indian Heart J 2008; 60(6): 554 – 557.

3) Steinberg BA, Moghbeli N, Buros J, Ruda M, Parkhomenko A, Raju BS, García-Castillo A, Janion M, Nicolau JC, Fox KA, Morrow DA, Gibson CM, Antman EM. Global outcomes of ST-elevation myocardial infarction: comparisons of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI 25) registry and trial. Am Heart J. 2007 Jul; 154(1):54-61.

4) Boden WE, Eagle K, Granger CB. Reperfusion Strategies in Acute ST-Segment Elevation Myocardial Infarction A Comprehensive Review of Contemporary Management Options. J Am Coll Cardiol 2007; 50(10):917–29