Effect of Double Bolus Urokinase on Thrombolysis in Acute Myocardial Infarction

Rha, Seong Woon; Park, Sang Won; Lee, Eun Mi; Whang, Kyo Seung; Ahn, Jung Chun; Song, Woo Hyuk; Lim, Do Sun; Park, Chang Gyu; Kim, Young Hoon; Seo, Hong Seog; Shim, Wan Joo; Oh, Dong Joo; Ro, Young Moo

Abstract

BACKGROUND AND PURPOSE
Although thrombolytic strategies with streptokinase(STK) and tissue-type plasminogen activator(t-PA) in the treatment of acute myocardial infarction(AMI) have been studied in large-scale clinical trials in the western countries, such large-scale studies with urokinase(UK) are scanty. Even though UK is most commonly used thrombolytic agent for the treatment of AMI in Korea, there is no consensus on the dosage and the way of administration of UK in patients with AMI. Accordingly, a prospective clinical study was performed to evaluate the effects of thrombolytic strategies of intravenous double bolus method and standard double-infusion method with different dosage of UK in the treatment of AMI.
SUBJECTS AND METHODS
Ninety there patients with AMI(male 75, female 18, age 57.5+/-10.8 years) were studied. The patients were divided into 3 groups according to dosage of UK and method of administration. Group I : 19 patients who received 1.5 million U of UK IV bolus, followed by 1.5 million U IV infusion for an hour(High Dose Group). Group II : 34 patients received 20,000U/kg body weight of UK IV bolus, followed by 20,000U/kg IV infusion for an hour(Double Dose Group). Group III : 40 patients received 1.5 million U of UK IV bolus and followed by 20,000U/kg IV bolus in 30 minutes with total dose of no more than 3 million U(Double Bolus Group). Coronary angiography(CAG) and left ventriculography(LVG) were performed 90 minutes after the administration of UK and post-AMI 7-10 days to investigate the patency of infarct-related artery(IRA) and LV function. Patency of IRA was graded according to the extent of flow of IRA. TIMI grade 0-1 was regarded as occluded, and grade 2-3 flow as patent. LV ejection fraction(EF) by echocardiography was measured on day 1, day 7-10 and 1 month after AMI. Indirect clinical parameters of thrombolysis were evaluated and were compared with CAG findings.
RESULTS
1) The 90 minutes IRA patency in Group III(Double bolus ; 79.0%) was higher than that in Group 1, but showed no statistically significant difference(High dose ; 61.5%, p=0.790). The 90 minutes IRA patency in Group III showed borderline significance with Group II(Double dose ; 57.1%, p=0.057). TIMI flow III in Group III(60.6%) was significantly higher than that in Group II(53.6%, p=0.0468) but showed no statistically significant difference with Group I(61.5%, p=0.158). 2) The EF by LVG were 49.1% in Group I, 41.7% in Group II and 49.2% in Group III. The difference in EF between Group I and Group III vs Group II was significant(p=0.008 in Group I, p=0.014 in Group III vs Group II). 3) Fatal bleeding complications(1 intracranial hemorrhage and 1 gastric ulcer bleeding) developed in Group II (Double dose). 4) Pain to door time, pain to needle time and door to needle time tended to be shorter in open(TIMI flow II-III) IRA group than in closed IRA group. 5) Initial EF were similar between open IRA group and closed IRA group(46.1% and 42.1% ; p=NS). The EF of open IRA group measured by LVG on initail coronary angiography(41.8% in closed IRA vs 48.0%, in open IRA, p=0.03) and by 2D-Echo on 7-10 day(41.7% in closed IRA vs 51.0% in open IRA, p=0.004) were better than those of closed IRA group. 6) Indirect clinical indices of reperfusion such as mean CPK peak, time to CPK peak significantly lower in open IRA group than in closed IRA group. 7) Fatal bleeding complications(1 intacranial hemorrhage and 1 gastric ulcer bleeding) developed in closed IRA group.
CONCLUSION
The findings we observed in this trial showed that earlier initiation and more rapid infusion of UK were associated with more increased 90min patency of infarct-related artery and more improved LV function without any obviously increased bleeding complications or other serious life-threatening complications than conventional UK therapy. Specifically, double bolus IV injection of UK(1.5 million U bolus followed by 20,000 U/Kg bolus in 30min)was more effective method of thrombolysis than conventional method for achieving optimal reperfusion in AMI patients. Also, IRA patency at 90 minutes after the initiation of thrombolysis was important in preserving global LV function in early recovery phase of AMI. Further trials may be needed to determine more effective thrombolysis with UK in AMI.