Safety and efficacy of thrombolysis with alteplase (50 mg) plus tirofiban versus alteplase (100 mg) alone in acute myocardial infarction: preliminary findings.
BACKGROUND: The goal of therapy in acute myocardial infarction (AMI) is the complete and timely restoration of coronary blood flow. Platelets have a pivotal role in the pathophysiology of AMI. The study was aimed at evaluating the safety and efficacy of the combination of 50 mg alteplase plus tirofiban vs 100 mg alteplase in AMI patients. METHODS: One hundred twenty patients (83 males, 37 females; mean age 54.3 +/- 8 years) were hospitalized for suspected AMI within 6 hours of the onset of symptoms. All patients presented pain and persistent ST-segment elevation, were suitable candidates for thrombolysis (1st episode) and were randomized (double blind) into two groups. Group A (n = 60,42 males, 18 females) received 50 mg alteplase (15 mg as bolus, followed by an infusion of 35 mg over 60 min) in combination with tirofiban (0.4 mcg/kg/min for 30 min followed by an infusion of 0.1 mcg/kg/min for 3 days). Group B (n = 60, 41 males, 19 females) received 100 mg of accelerated-dose alteplase alone. Reperfusion criteria were defined as follows: > 50% reduction in the ST-segment elevation; resolution of chest pain; double marker of creatine kinase (CK) and CK-MB activity 2 hours after the start of thrombolysis; reperfusion arrhythmias within the first 120 min of thrombolysis. The blood pressure, heart rate and ECG were continuously monitored. The mortality, re-AMI, recurrent angina, major and minor bleeding, and emergency bypass surgery or coronary angioplasty were checked. RESULTS: The groups were similar with regard to clinical data, risk factors, time elapsed from the onset of symptoms to thrombolytic therapy and AMI localization. Forty-seven patients (78.3%) from group A showed reperfusion (15-60 min) vs 25 patients (41.7%) from group B (43-105 min after the end of full-thrombolysis, p = 0.01). Group A patients showed an earlier CK peak and lower CK and CK-MB peaks than those in the control group (p = 0.0001, p = 0.011, p = 0.005, respectively). Nine patients (7.5%) died: 6 (10%) in group B and 3 (5%) in group A (p = NS). A non-fatal re-AMI occurred in 8 patients from group A and in 4 patients from group B (p = NS). Recurrent angina occurred in 27 patients (45%) from group A and in 11 (18.3%) from group B (p = 0.037). Twenty-three of these patients underwent urgent coronary angioplasty (17 from group A and 6 from group B) and 3 from group A and 1 from group B underwent urgent coronary artery bypass grafting (p = NS). The frequency of minor bleeding was higher in group A than in group B (56.7 vs 25%, p = 0.033). No major bleeding was observed in the study groups. At the predischarge echocardiogram, the ejection fraction was higher in group A than in group B (50 +/- 9 vs 44 +/- 7%, p = 0.001). CONCLUSIONS: Our data suggest that the combination of glycoprotein IIb/IIIa inhibitors plus alteplase is feasible in AMI patients and that the increased risk of bleeding is an acceptable risk considering the advantage in terms of the reduction in the extent of an AMI. In addition, this combination can allow one to gain time when it is necessary to perform mechanical revascularization in patients admitted to a hospital without an interventional cardiology laboratory or in those who have to be referred to another hospital for urgent coronary artery bypass grafting.