Comparison of reperfusion regimens with or without tirofiban in ST-elevation acute myocardial infarction

Abstract

There is continued debate as to whether a combined reperfusion regimen with platelet glycoprotein IIb/IIIa inhibitors provides additional benefit in optimal myocardial reperfusion of patients with a ST-elevation acute myocardial infarction (AMI). In addition, the best angiographic method to evaluate optimal myocardial reperfusion is still controversial. Patients (n = 144) with a first AMI presenting <6 hours from onset of symptoms were randomized to receive a conjunctive strategy (n = 72) with low-dose alteplase (50 mg) and tirofiban (0.4 microg/kg/min/30 minute bolus; infusion of 0.1 microg/kg/minute), or tirofiban plus stenting percutaneous coronary intervention (PCI). Control patients (n = 72) received standard strategy with either full-dose alteplase (100 mg) or stenting PCI [correction]. All patients were submitted to coronary angiographic study at 90 minutes. The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow at 90 minutes. Secondary end points were TIMI myocardial perfusion (TMP) rates, a composite end point at 30 days (death, reinfarction, refractory ischemia, stroke, heart failure, revascularization procedures, or pulmonary edema), and bleeding or hematologic variables. The rate of TIMI 3 flow at 90 minutes for patients treated with alteplase alone was 42% compared with 64% for those who received low-dose alteplase and tirofiban. Standard stenting PCI achieved 81% of TIMI 3 flow compared with 92% when tirofiban was used. Significantly higher rates of TMP grade 3 were observed when tirofiban was used as the adjunctive treatment in both alteplase (66% vs 47%) and stenting PCI (73% vs 55%). Higher rates of the composite end point were observed in standard regimens compared with conjunctive regimens (hazard ratio 5.8, 95% confidence interval 1.27 to 26.6, p = 0.023). Regardless of reperfusion regimen, better outcomes were observed when a combination of TIMI 3 flow and TMP grade 3 was achieved. Beyond TIMI 3 flow rate, the TMP grade was an important determinant. The rates of major bleeding were similar (2.8%) for standard versus conjunctive regimens with tirofiban. Thus, tirofiban as a conjunctive therapy for lytic and stenting regimens not only improves TIMI 3 flow rates, but also the TMP3 rates, which are related to a better clinical outcome without an increase in the risk of major bleeding. This study supports the hypothesis that platelets play a key role not only in the atherothrombosis process, but also in the disturbances of microcirculation and tissue perfusion.