| Objectives:The purposes of the present study are: ①to evaluate efficacy of tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, in the treatment of unstable angina and non-Q-wave myocardial infarction. ② to demonstrate the mechanism of the platelet glycoprotein IIb/IIIa receptor tirofiban in patient with acute coronary syndrome.③to investigate safety of tirofiban therapy in Chinese patients with acute coronary syndrome.④ to evaluate antithrombotic effect of the platelet glycoprotein II b/IIIa receptor inhibitor tirofiban in patient with acute coronary syndrome during percutaneous coronary intervention.Methods:A total of 204 patients with UA/NSTEMI underwent randomization between the patients of 18-70 years old in 3 hospitals. we did a multi-center, randomized, double-blind, placebo controlled trial Patients with UA/NSTEMI were randomized to receive placebo plus heparin or tirofiban HC1 plus heparin: tirofiban (0.4μg per kilogram of body weight per minute for 30 minutes, followed by an infusion of 0.1μg per kilogram per minute) plus adjusted dose of heparin or adjusted-dose of heparin plus placebo. Heparin was administered as an intravenous bolus of 5000 units, followed by an infusion of 1000 units per hour, adjusted after 2~4.5 days (because of the high occurrence of hemorrhagic complication during the study, with the permission of ethic committee, the dose of heparin was adjusted to the half of the before, whether in burden dose or maintenance dose, so as to keep the APTT ranges in 1.5-2 times of the normal value). Tirofiban placebo was given to the patients in the control group, and the aspirin and heparin were accompanied simultaneously, whose doses were the same as the study group. Aspirin (50mg) was administered to all patients daily and for 2~4.5 days. Results:1. A total of 200 patients with UA/NSTEMI underwent randomization, 101 patients in the study group and 99 patients in the control group. The study drugs were infused for a mean (±SD) of 4.02±0.74 days. In the control group, the figure were 4.05±0.68 days (p>0.05). No important difference was detected among the groups of the baseline characteristics (age, sex, body mass index, blood pressure, electrocardiogram, time of chest pain, concomitant therapy, and diagnosis).2. The primary end point and composite end point Compared with the control group, there was a significant reduction of the rate of the composite end point of death, new myocardial infarction, and refractory ischemia in 30 days in the group received the combination of tirofiban and heparin (13.9% vs 29.3%, p=0.010); The risk of the composite end point of death or new myocardial infarction was reduced by 77.5 percent in 4.5 days; 57.7% in 30 days. Although without statistically difference, there exited a trend of reduction in different time and index which was primarily due to 77.5% decrease in the risk of myocardial infarction and 45% decrease in the risk of death in 4.5 days, as compared with the risk in the heparin-only group.3. Inhibition of platelets aggregation rate The inhibition of platelets aggregations was significantly greater in study group than control group (p<0.01).4. Effects of tirofiban group versus heparin alone on CK-MB level In the study group, the serum CK-MB level began to decrease after 12 hours after treatment and was significantly lower than before the treatment 2 days later (p <0.05); while in the control group the serum CK-MB level began to decrease 1 days later, however, without statistical difference.5. Hemorrhagic complication Thrombocytopenia and bleeding are potential side effects of GP IIb/IIIa receptor antagonists. GPIIb/IIIa receptor inhibitors were associated with an increased risk of bleeding complications compared with control, however, bleeding complication were not significantly different between the two treatment groups (12.7% vs 7.0%, p>0.05). To decrease the occurrence of bleeding complication, the dose of heparin was adjusted during the middle period of this study. After adjustment, the occurring rate of hemorrhage was 7.8% in the study group, which was 51.3% lower than before treatment, and the occurring rate of hemorrhage in the control group was dropped from 7.7% to 5.4%, 29.9% lower than beforetreatment. Conclusions:The combination of the tirofiban with heparin and aspirin has the confirmed therapy effect on ACS: on the basis of the sufficient treatment of anticoagulation and anti-ischemia, it can reduce the occurrence of cardiovascular complications, the mortality and morbidity of the myocardial infarction, as well as the occurrence of the combined end point, which will benefit those patients of UA/NSTEMI who are not scheduled to undergo coronary revascularization, with the similar therapeutic effect.
|
PDF Full Text Request