Acute ST-segment elevation myocardial infarction (STEMI) is a serious medical condition, affecting people

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1 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 Nakorn Sithinamsuwan, MD, Sopon Sanguanwong, MD, Pachum Tasukon, MD, Prasart Laothavorn, MD, Chumpol Piamsomboon, MD, Channarong Naksawadhi, MD, Preecha Uearojanangkul, MD, Nakarin Sansanayudh, MD, Waraporn Tiyanon, MD, Verapon Pinphanichakarn, MD Division of Cardiology, Department of Medicine, Phramongkutklao Hospital. Bangkok, Thailand Abstract 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 : E-Journal : 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 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

2 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 Nakorn Sithinamsuwan, MD 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, 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

3 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 were 1) patients with hemodynamic instability (in particular cardiogenic shock, severe heart failure, and ventricular arrhythmia), 2) history of sudden cardiac arrest, 3) liver impairment (i.e. cirrhosis or hepatitis), and 4) contraindications to thrombolytic agents (1). All patients gave informed consent. The protocol was approved by the Phramongkutklao hospital ethical review board (protocol R075h/49, see the appendix). Randomization process Eligible patients were randomly assigned with a stratified randomization method to receive either TNKtPA or primary PCI. We used two important parameters for classifying the patient groups, which were 1) duration of angina and 2) history of previous MI (Figure 1). Treatment strategies Every patient received all standard medical care from American College of Cardiology (ACC)/American Heart Association (AHA) 2007 guidelines for management of patients with STEMI, including chewable aspirin 300 mg, oxygen, nitrate, and morphine, starting at the time of enrollment. Patients who were randomly assigned to primary PCI received unfractionated heparin to achieve an activated clotting time of 300 to 350 seconds during the invasive procedure. Platelet glycoprotein IIb/IIIa receptor blockers or heparin infusion after the procedure was given individually according to the physicians judgment. All infarct-related arteries (IRA) were treated if they were found to be significantly stenosed or totally occluded. Stenting with bare-metal stents was attempted in all patients. Angioplasty of non IRAs was not performed. Patients were not considered for immediate coronary artery bypass grafting unless severe hemodynamic instability occurred. Clopidogrel 75 mg was given daily for at least one month after stenting, aspirin mg/day was given indefinitely. TNK-tPA was given in a single bolus intravenously within 5-10 seconds to patients who were randomly assigned to fibrinolysis. Dosage was adjusted by body weight, Table 1. A dose of unfractionated heparin 60 units/ kg (maximum 4,000 units) was bolusly injected and then was continuously infused for three days with a starting dose of 12 units/kg/hour, followed by titrating up until the acceptable activated partial thromboplastin time of seconds was reached. Table 1. Dosage of TNK-tPA adjusted by body weight (16) Body weight (kg) Dose (mg) < Rescue PCI was done in whom fibrinolysis had failed (i.e. when ST-segment elevation less than 50% resolved after 90 minutes following initiation of fibrinolytic therapy in the lead showing the worst initial elevation, ongoing chest pain, cardiogenic shock and severe heart failure) after 90 minutes of fibrinolysis. In addition, all patients underwent coronary angiography (CAG) within seven days after fibrinolysis to assess the degree of stenosis; the angioplasty with balloon and bare-metal stents would be performed if indicated. Endpoints: We assessed the endpoint that occurred within 30 days after randomization. We followed up patients in the medical ward, cardiology clinic and by telephone calls. Furthermore, we assessed the patients in the medical ward if they were re-admitted. The primary endpoint was a composite of death from cardiac causes, clinical reinfarction and disabling stroke within 30 days of followup. However, procedure-related re-infarction was not included in this primary endpoint. Secondary endpoints were recurrent ischemia, heart failure, cardiogenic shock, arrhythmia, repeat revascularization (rescue PCI, further PCI), coronary artery bypass graft, usage of intra-aortic balloon pump (IABP), mechanical ventilator requirement, major bleeding, cost and length of stay within 30 days. Reinfarction was diagnosed if there was recurrent chest pain lasting longer than 30 minutes with new ST-T changes and elevation of creatine kinase MB (CK-MB) mass of at least 50% greater than prior value. Recurrent ischemia was diagnosed if there was recurrent chest pain lasting longer than 20 minutes with new ST-T changes. Disabling stroke was defined as a fatal stroke or a stroke causing clinically significant mental or physical handicaps within

4 30 days of follow-up. Severe bleeding was defined as intracranial hemorrhage or bleeding that caused hemodynamic compromise. Moderate bleeding was defined as bleeding that required blood transfusion without any unstable vital signs. Statistic analysis Data are presented as number, percentage, mean, and standard deviation (SD). The data are presented as median and range if the distribution was not normal. Chisquare analysis or Fisher-exact test was used to compare Nakorn Sithinamsuwan, MD categorical data. The t-test and Mann-Whitney U test were used to compare continuous data. A P-value less than 0.05 represented a statistically significant difference. We performed statistical analysis using SPSS program version Results Forty patients with acute STEMI were enrolled in our study over a seven-month period; however, 16 patients were excluded due to either late onset (>12 hrs), were hemodynamically unstable, or had a contraindication to Table 2. Patients demographics, underlying diseases and concomitant drug usage Profile Overall N = 24 (%) Fibrinolysis PCI p-value Age (year) [Mean ± SD / (range)] 59.3 ± 16.6 (22-86) 61.8 ± 12.9 (36-79) 56.8 ± 19.9 (22-86) Male sex 18 (75%) 8 (66.7%) 10 (83.3%) Body mass index (kg/m2) 23.7 ± ± ± 3.8 Diabetes mellitus 5 (20.8%) 3 (25%) 2 (16.7%) Dyslipidemia 7 (29.2%) 4 (33.3%) 3 (25%) Smoking 11 (45.8%) 5 (41.7%) 6 (50%) Hypertension 12 (50%) 7 (58.3%) 5 (41.7%) Previous SBP (mmhg) ± ± ± 27.9 Previous DBP (mmhg) 78.8 ± ± ± 16.5 Previous MI 1 (4.2%) 0 1 (8.3%) Previous stroke 1 (4.2%) 1 (8.3%) 0 Chronic kidney disease 2 (8.3%) 0 2 (16.7%) Aspirin 3 (12.5%) 2 (16.7%) 1 (8.3%) Clopidogrel 1 (4.2%) 1 (8.3%) 0 Nitrate 2 (8.3%) 2 (16.7%) 0 Statin 6 (25%) 3 (25%) 3 (25%) Beta-blocker 6 (25%) 4 (33.3%) 2 (16.7%) Calcium antagonist 1 (4.2%) 0 1 (8.3%) ACEI 2 (8.3%) 1 (8.3%) 1 (8.3%) ARB 1 (4.2%) 0 1 (8.3%) Diuretic agent 2 (8.3%) 1 (8.3%) 1 (8.3%) PCI = Percutaneous coronary intervention, SD = Standard deviation, = not significant, ACEI = Angiotensin converting enzyme inhibitor, ARB = Angiotensin receptor blocker

5 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 Figure 2. Study algorithm tenecteplase (Figure 2), and therefore only 24 patients were eligible for randomization. After randomization, there were 12 patients in the fibrinolytic group and 12 patients in the PCI group. The patient s demographic characteristics are shown in Table 2. Overall, mean age of the patients was 59 ± 16.6 years (range years). Seventy five percent of them were males (male to female ratio of 3:1). The mean body mass index was 23.7 ± 6.6 kg/m 2 (range kg/m 2 ). The two most common risk factors in MI were hypertension and smoking, which were present in half of them. Diabetes mellitus and dyslipidemia were diagnosed in approximately 20-30% of the studied population. A few cases had taken antiplatelet agents prior to the coronary events; they were aspirin (12.5%) and clopidogrel (4.2%). Statins and beta-blockers were used in 25%. The mean age of patients in the thrombolytic group was 61.8 ± 12.9 years, higher than that of the PCI group, which was 56.8 ± 19.9 years, however, there was no statistically significant difference (p value 0.48). The proportion of males in the PCI group was greater than that of the other group (83% VS 67%, p value 0.34). Nevertheless, all baseline demographic characteristics, risk factors, concomitant drugs used were not different between the patients of the two groups (Table 2). The overall cardiac parameters and medical treatments in both groups are compared in Table 3. Overall, the ECGs revealed inferior-wall STEMI in 70% and anterior-wall STEMI in 30% of the patients. The time from the symptom onset to randomization was 2.1 hours in the thrombolytic group and 2.5 hours in the PCI group, (p value 0.62). The times from the ER presentation to treatment were 116 and 122 minutes for the thrombolytic and the PCI groups respectively (p value 0.9). The mean ejection fraction was 53.2 ± 12.5% in the thrombolytic group and 50.8 ± 11.4% in the PCI group (p value 0.64). Regarding the results of CAG, there were 54.2% with single vessel disease, 16.6% with double vessel disease and 29.2% with triple vessel disease. Serum creatinine concentration was lesser in the thrombolytic group than in the PCI group (p value 0.04). Intravenous heparin was given to all patients of both groups. By contrast, the continuous intravenous heparin infusion was given in all the thrombolytic patients, but in only six of the PCI patients. Antiplatelets were given to all patients: aspirin (100%) and clopidogrel (95%). Other important medications prescribed were statins (92%), nitrates (62%), beta-blockers (58%) and angiotensin converting enzyme inhibitors (46%). The medications prescribed before the discharge period did not differ between groups. There was no death within 30 days after randomization in both groups, Table 4. In the PCI group, there was 1 patient whose clinical aspect was compatible with the primary endpoint. He suffered from cardiac re-infarction and also developed disabling hemorrhagic stroke. This re-infarction was caused by acute stent thrombosis that needed repeat revascularization. Meanwhile, he developed sudden right hemiparesis with motor aphasia, computer tomography (CT) of the brain revealed a large left hemispheric hemorrhage. Regarding the secondary endpoint, half of the patients randomly assigned to the thrombolytic agent showed inadequate reperfusion on coronary angiographic study and required further PCI, due to the severe residual stenosis of the infarct-related

6 Nakorn Sithinamsuwan, MD Table 3. Cardiac parameters and medical treatment of acute coronary syndrome. Profile Overall N = 24 (%) Fibrinolysis PCI p-value Onset to presence at ER [Mean ± SD (range)] (hours) 2.3 ± 2.3 (0.2-10) 2.1 ± 1.6 (0.2-5) 2.5 ± 2.8 (0.5-10) Presence at ER to treatment [Mean ± SD (range)] (minutes) ± (30-420) ± (30-330) ± 105 (30-420) Heart rate (beat/minute) [Mean ± SD (range)] 72.2 ± 19.9 (40-120) 70.7 ± 20.5 (40-120) 73.7 ± 20.2 (47-110) Current systolic pressure (mmhg) ± ± ± 28.5 Current diastolic pressure (mmhg) 76.2 ± ± ± 20.5 Anterior wall infarction 7 (29.2%) 3 (25%) 4 (33.3%) Inferior wall infarction 17 (70.8%) 9 (75%) 8 (66.7%) Killips I 23 (95.8%) 12 (100%) 11 (91.7%) Killips II 1 (4.2%) 0 1 (8.3%) LVEF from echocardiogram (%) [Mean ± SD (range)] 52.0 ± 11.8 (28-76) 53.2 ± 12.5 (40-76) 50.8 ± 11.4 (28-68) RWMA 16 (69.6%) 9 (75%) 7 (63.6%) Reverse E/A ratio 13 (56.5%) 6 (50%) 7 (63.6%) Single vessel disease 13 (54.2%) 7 (50%) 6 (41.7%) Double vessel disease 4 (16.6%) 2 (16.7%) 2 (16.7%) Triple vessel disease 7 (29.2%) 3 (25%) 4 (33.3%) Creatinine (mg/dl) [Mean ± SD (range)] 1.1 ± 0.2 ( ) 1.0 ± 0.1 ( ) 1.2 ± 0.3 ( ) 0.047* Aspirin 24 (100%) 12 (100%) 12 (100%) - Clopidogrel 23 (95.8%) 12 (100%) 11 (91.7%) Nitrate 15 (62.5%) 6 (50%) 9 (75%) Statin 22 (91.7%) 12 (100%) 10 (83.3%) Beta-blocker 14 (58.3%) 7 (58.3%) 7 (58.3%) ACEI 11 (45.8%) 6 (50%) 5 (41.7%) CCB 1 (4.2%) 0 1 (8.3%) Diuretic drug 1 (4.2%) 0 1 (8.3%) GP IIb/IIIa inhibitor 5 (20.8%) 3 (25%) 2 (16.7%) Heparin 18 (75%) 12 (100%) 6 (50%) ** 0.007* Inotropic drug 11 (45.8%) 7 (58.3%) 4 (33.3%) * p value < ** All PCI patients received heparin during the procedure, but six of them received further infusion. PCI = Percutaneous coronary intervention, ER = Emergency room, SD = Standard deviation, = not significant, LVEF = left ventricular ejection fraction, ACEI = Angiotensin converting enzyme inhibitor, ARB = Angiotensin receptor blocker

7 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 Table 4. Endpoints, complicationsand further procedural requirements within 30 days Profile Overall N = 24 (%) Fibrinolysis PCI p-value Death Recurrent myocardial infarction 1 (4.2%) 0 1 (8.3%) Stroke 1 (4.2%) 0 1 (8.3%) Rescue PCI Further PCI *** 7 (29.2%) 6 (50%) 1 (8.3%) 0.025* Intubation & ventilator 4 (16.7%) 0 4 (33.3%) 0.047* Intraaortic balloon use 4 (16.7%) 0 4 (33.3%) 0.047* Coronary bypass surgery Recurrent cardiac ischemia 2 (8.3%) 1 (8.3%) 1 (8.3%) Heart failure 1 (4.2%) 0 1 (8.3%) Cardiogenic shock 3 (12.5%) 0 3 (25%) Arrhythmia 1 (4.2%), VT 1 (8.3%) 0 Bleeding complication 3 (12.5) 0 3 (25%) Re-admission within 30 days 1 (4.2%) 1 (8.3%) ** 0 * p-value <0.05, ** admission for elective PCI. *** Elective PCI within 7 days. coronary artery, which was significantly greater in number in comparison to the PCI group (p value 0.02). There was no neither respirator nor IABP requirement in the thrombolytic group, which was a significant difference in comparison to the PCI group (required in 66.6%), p value In the PCI group, we found that patients had more minor hemorrhagic events (gross hematuria and coffee grounds gastro-intestinal bleeding) than that in the thrombolytic group (p value 0.10), Table 4. Overall, the median duration of coronary care unit (CCU) stays and hospital stays was 4.4 and 8.7 days respectively. The duration of hospital stay in the PCI group was almost twice as long as in the thrombolytic group (p-value 0.95 and 0.88 for CCU and hospital time respectively). The PCI group not only spent longer in admission time, but the cost of treatment was more than the other group. From cost analysis, the cost of treatment in the PCI group was higher than the thrombolytic group by approximately 50,000 baht/patient, Table 5. Discussion Early, complete, and sustained reperfusion of the IRA improves survival in patients presenting with ST-segment elevation myocardial infarction (1). Reperfusion with thrombolysis or percutaneous coronary intervention is the current standard of care for STEMI (1). In a large cohort, primary angioplasty is superior to fibrinolysis for patients with STEMI (3-14). Although fibrin specific thrombolytic agents can achieve early patency of the IRA, complete flow is restored in 60% of patients (10, 16). Angioplasty accomplishes this in up to 95% of patients and is associated with a lower rate of re-occlusion (10); however, delays associated with patient transference and the catheterization team, plus the limited accessibility to catheterization facilities, might significantly prolong the time to mechanical reperfusion. The purpose of this study was to compare clinical outcomes after the use of primary PCI and immediate thrombolytic therapy with TNK-tPA in the ER in patients

8 Nakorn Sithinamsuwan, MD Table 5. Admission time and cost assessment Profile Overall (N = 24) Fibrinolysis (N = 12) PCI (N = 12) p-value CCU stay (day) [Median (range)] 4.4 (0-32) 3 (1-7) 5.8 (0-32*) Hospital stay (day) [Median (range)] 8.7 (3-55) 6.8 (3-13) 10.6 (3-55*) Cost (baht) [Median (range)] 216,283 (12, ,441) 191,960 (77, ,430) 248,714 (12, ,441*) * The same patient that suffered from acute stent thrombosis, intracranial hemorrhage, sepsis, pneumonia and prolong CCU stay and hospital stay. presenting with acute uncomplicated STEMI in our center. The reason why we selected TNK-tPA as the thrombolytic agent for this study is it has highly fibrin-specific, weight adjusted, longer half-life that allows a single bolus administration, resistance to inhibition by plasminogen activator inhibitor type 1, and is associated with fewer major bleeding complications when coupled with a reduced dose of heparin (15-18). The combined endpoint, including death, reinfarction, and stroke, at 30 days occurred in only one patient of the PCI group. Furthermore, the PCI group tended to have more consequences such as congestive heart failure, cardiogenic shock, ventilator and IABP dependence and bleeding complications than the thombolytic group. This would be related to a delay reperfusion process. Moreover, we found that, this complicated patients in the PCI group which had low ejection fraction (less than 40%) and multivessel disease. TNK-tPA could restore normal coronary blood flow in 50% of pateints, while the other half of patients had free symptoms and underwent elective PCI within 7 days. These results suggest that a strategy of immediate TNK-tPA intravenous therapy in the ER with further PCI may be safer or at least equal to primary angioplasty. Nevertheless, our primary endpoints were fewer than expected. The difference in outcome between ours and other trials may relate to the technical results of the angioplasty itself. Additionally, several factors may have contributed to the dissimilarity, including low risk factors, relatively short symptom-onset to presenting times, aggressive revascularization during the index hospitalization, and rigorous application of practice guidelines in prescribing aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, and lipidlowering drugs. However, our pilot study was performed in only uncomplicated STEMI (hemodynamically stable). The efficacy and tolerability results themselves cannot be applied as standard strategies for high-risk STEMI. In a randomized study (10), patients presenting with high-risk STEMI, TNK plus immediate angioplasty reduced the risk of recurrent ischemic events compared with TNK alone and was not associated with an increase in major bleeding complications. Thus, combined treatment would be an efficient strategy to combat this severe condition. Limitations and future directions Our pilot study was conducted at a selected hospital site (a single center) and involved a small number of patients. A low rate of outcomes was detected. Endpoints and adverse events in our study were too small to provide reliable efficacy and tolerability data. Therefore, we recommend further study with a large sample size number. Also, in the future this trial should be performed in several medical centers (as a multi-center study across the country) because this can provide an adequate sample size and can reduce the confounding factors.

9 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 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. Acknowledgement We are grateful to all staffs, medical personnel in the Emergency Department, the Coronary Care Unit and Medical Wards of Phramongkutklao Hospital, who contributed immensely to the care of patients. We also thank all patients enrolled in our study. References 1. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol 2004; 44: E1-E Tanomsup S, Sritara P, Suithichaiyakul T, et al. Thai Acute Coronary Syndrome Registry, What have we learned? The Heart Association of Thailand under the Royal Patronage Aug 2002 July ACS_Registry_update_10_Sep_ 05.pdf. 3. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. The Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1993; 328: A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. N Engl J Med 1997; 336: Tiefenbrunn AJ, Chandra NC, French WJ, Gore JM, Rogers WJ. Clinical experience with primary percutaneous transluminal coronary angioplasty compared with alteplase (recombinant tissue-type plasminogen activator) in patients with acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). J Am Coll Cardiol 1998; 31: Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 2003; 349: Berrocal DH, Cohen MG, Spinetta AD, et al. Early reperfusion and late clinical outcomes in patients presenting with acute myocardial infarction randomly assigned to primary percutaneous coronary intervention or streptokinase. Am Heart J 2003; 146: E Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis. Circulation 2003; 108: Mehta RH, Sadiq I, Goldberg RJ, et al. Effectiveness of primary percutaneous coronary intervention compared with that of thrombolytic therapy in elderly patients with acute myocardial infarction. Am Heart J 2004; 147: Le May MR, Wells GA, Labinaz M, et al. Combined angioplasty and pharmacological intervention versus thrombolysis alone in acute myocardial infarction (CAPITAL AMI study). J Am Coll Cardiol 2005; 46: Svensson L, Aasa M, Dellborg M, et al. Comparison of very early treatment with either fibrinolysis or percutaneous coronary intervention facilitated with abciximab with respect to ST recovery and infarct-related artery epicardial flow in patients with acute ST-segment elevation myocardial infarction: the Swedish Early Decision (SWEDES) reperfusion trial. Am Heart J 2006; 151: 798 e Grines CL, Westerhausen DR, Jr., Grines LL, et al. 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10 Nakorn Sithinamsuwan, MD ก ก ก ก ก ก (Percutaneous coronary intervention, PCI) ก ก ก ST elevation myocardial infarction (STEMI) (ก ก TNK-tPA ) ก,., ก,.,,.,,.,,., ก,., ก,.,,.,,., ก,. ก ก ก ก ก : ก ก ก ก ก (PCI) ก ก ก STEMI ก ก : ก ก STEMI 12 ก ก ก ก ก Ventricular arrhythmia ก ก ก ก ก TNK-tPA ก ก (PCI) ก ก ก ก 7 ก ก ก ก ก ก ก ก 30 ก ก ก ก Ventricular arrhythmia ก ก (Coronary artery bypass graft, CABG) ก ก (Intra-aortic balloon pump, IABP) ก ก ก 30 ก ก : ก ก 24 ก 40 ก 2 ก ก ก ก ก 2.1 ± ± 2.8 ก ก PCI ก ก ก ก ก 116 ± ± 105 ก ก PCI ก PCI ก ก ก ก PCI ก ก กก ก (6/12 ) ก ก ก ก (PCI) ก 191,960 ±110, ,714 ± 266,854 ก ก PCI ( p 0.95) 6 ± ± 14 ก ก PCI ( p 0.88) : กก ก ก ก ก STEMI ก ก TNK-tPA ก ก ก