A Comparison of Immediate Thrombolytic Therapy in the Emergency Department versus Primary Percutaneous Coronary Intervention in Patients with Acute ST Elevation Myocardial infarction (STEMI) : A Pilot Study of TNK-tPA Used in Thai Patients

Objective: To compare the outcome after immediate thrombolytic therapy in the emergency department versus primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) in Phramongkutklao Hospital. Methods: We prospectively enrolled 24 hemodynamically stable acute STEMI patients presenting within 12 hours of the clinical onset. All of them were treated with standard medical regimen, and then randomly assigned to undergo primary PCI or to receive intravenous thrombolytic therapy with tenecteplase tissue type plasminogen activator (TNK-tPA) in the emergency department followed by standard care. Coronary angiography was performed within 1 week after thrombolysis in all patients. The primary endpoint was a composite of outcomes of death, recurrent myocardial infarction (MI) and stroke at 30 days. The secondary endpoints were recurrent ischemia, heart failure, cardiogenic shock, arrhythmia, repeat revascularization (rescue PCI, further PCI), coronary artery bypass graft (CABG), usage of intra-aortic balloon pump (IABP), mechanical ventilator support, major bleeding, cost and length of stay at 30 days. Results: Twenty-four patients with acute STEMI were enrolled. The median time interval from symptom onset to random assignment was 2.1 hours in the TNK-tPA group and 2.5 hours in the PCI group. The median time to needle and time to balloon inflation were 116 minutes and 122 minutes respectively, (p = 0.90). The primary end-point was only one patient in the PCI group had re-infarction and hemorrhagic stroke. However, half of the patients in the thrombolytic group still required further PCI. The cost was 248,714 ± 266,854 baht in the PCI group and 191,960 ± 110,029 baht in theTNKtPA group (p = 0.95). The duration of hospital stay was 10.6 ± 14 days in the PCI group and 6 ± 3 days in theTNK-tPA group (p = 0.88). Conclusion: This pilot study shows that the immediate TNK-tPA intravenous therapy in the emergency department for treating patients with acute uncomplicated STEMI appears to be safe and may be a worthy alternative treatment in selected patients. Thai Heart J 2009; 22 : 69-78 E-Journal : http://www.thaiheartjournal.org Introduction Acute ST-segment elevation myocardial infarction (STEMI) is a serious medical condition, affecting people Corresponding author: Nakorn Sithinamsuwan, MD Division of Cardiology, Department of Medicine, Phramongkutklao Hospital. 315 Rajvithi road, Phrayathai district, Rachatavee, Bangkok, Thailand 10400. E mail address: Nink_MD@hotmail.com worldwide (1). It has been recognized that there are approximately 500,000 patients suffering annually in the United States from this condition (1). In Thailand, around 1,000 patients per year were diagnosed with STEMI (2). Additionally, our medical institute has had about 50 newly diagnosed STEMI patients per annum. It is widely accepted that STEMI is not only a common medical problem, but also a fatal condition. It occurs because of a clot-occluded coronary artery through multiple pathogeneses. Hence, cardiac muscle ischemia and then THAI HEART JOURNAL Vol. 22 No.3 July 2009 THAI HEART JOURNAL Vol. 22 No.3 July 2009 Nakorn Sithinamsuwan, MD infarction occur. The STEMI mortality in the GRACE registry and Thailand were 7% and 17% respectively (2). Prompt and complete restoration of coronary flow is the principal mechanism that improves survival and other clinical outcomes in patients with acute STEMI (1). Nevertheless, reperfusion therapy for STEMI is different among hospitals. At selected centers, coronary angioplasty, especially primary percutaneous coronary intervention (PCI), can be performed expeditiously in such patients, resulting in better coronary blood flow and 30-day survival rates than patients who received intravenous thrombolytic therapy (3-14). In general, the problem is that a PCI facility is available in only certain medical centers, so that physicians need to choose other available treatments. Another standard strategy to combat acute STEMI is intravenous thrombolytic therapy. It has many favorable properties such as high efficacy, widespread availability and reduces mortality in some reports (16). Therefore, this strategy has been used in more than a million patients over the past decade (1). Tenecteplase tissue type plasminogen activator (TNK-tPA) is a thrombolytic agent, which has been recently used. It is a variant of the native tissue type plasminogen activator (tPA) molecule that has a 16-fold greater fibrin specificity than alteplase, a longer half-life, slower plasma clearance, and 80-fold greater resistance to inhibition by plasminogen activator inhibitor type 1 (15-18). Its half-life of 18 minutes allows a singlebolus administration. Moreover, in comparative clinical trials, tenecteplase was found to have equivalent efficacy to recombinant tPA (alteplase) (17-18). The rate of intracranial hemorrhage with tenecteplase was similar to that with alteplase, and tenecteplase was associated with fewer non-cerebral complications and less need for blood transfusions (17). Furthermore in the Thai Acute Coronary Syndrome (ACS) Registry (2), the average door-to-balloon time in the Primary PCI group were more than 120 minutes, so thrombolytic therapy may have a role in treating the STEMI patients. The use of TNK-tPA in the Emergency Department may further reduce the differences in outcome between thrombolysis and coronary intervention. Therefore, the aim of this study was to compare the outcome after immediate thrombolytic therapy in the emergency department versus primary PCI in patients with acute STEMI in Phramongkutklao Hospital. Methods Study design This study was a prospective randomized trial, performed at Phramongkutklao Hospital from June 1st to December 31st, 2007. Eligible patients Patients presenting within 12 hours after the onset of acute myocardial infarction, who had chest pain lasting at least 20 minutes, accompanied by electrocardiographic (ECG) with ST-segment elevation of at least 0.1 mV in two or more contiguous leads or new left bundle branch block or posterior wall myocardial infarction (MI) (STsegment depression at least 0.1 mV with tall R wave in lead V1-2), were eligible for enrollment. The exclusion criteria Figure 1. Stratified randomization flow chart