Clinical benefits of adjunctive tirofiban therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Background There is continued debate as to whether a combined reperfusion regimen with platelet glycoprotein IIb/IIIa inhibitor - tirofiban provides additional benefit in optimal myocardial reperfusion for patients with acute ST-segment elevation myocardial infarction (STEMI). This study was conducted to investigate the clinical benefits of adjunctive tirofiban therapy combined with primary percutaneous coronary intervention (PCI) in patients with STEMI. Methods One hundred and seventy-two consecutive patients with STEMI presented within 12 h of symptoms were randomly allocated to primary PCI combined with early (upstream group, n=57) or late administration of tirofiban (downstream group, n=57) or primary PCI treatment alone (control group, n=58). Clinical characteristics, angiographic findings, and in-hospital outcomes were compared between groups, as well as left ventricular ejection fraction (LVEF) and major adverse cardiac events (MACE, including death, reinfarction and target vessel revascularization) at 30-day and 6-month clinical follow-up. Results Despite comparable baseline clinical features among three groups, angiographic and procedural characteristics and outcomes differed significantly between patients receiving tirofiban treatment and controls, with respect to preprocedural (upstream: 28.1%, downstream: 7.0%, control: 5.2%, P < 0.001) and postprocedural thrombolysis in myocardial infarction (TIMI) grade 3 flow of infarct-related artery (98.2, 94.7, 86.2%, P=0.03), TIMI myocardial perfusion grade 3 (75.4, 70.2, 53.4%, P=0.03), corrected TIMI frame count (20.4 +/- 5.0, 23.1 +/- 5.3, 32.2 +/- 6.7, P < 0.001), resolution of the sum of ST-segment elevation (6.16 +/- 1.21, 6.02 +/- 1.09, 4.53 +/- 2.65 mm, P < 0.001), peak value of creatine kinase-M B (218.0 +/- 72.5, 224.2 +/- 69.4, 255.3 +/- 770 ng/ml, P=0.02) and troponin 1 (76.0 +/- 21.5, 79.8 +/- 18.7, 86.4 +/- 11.0 ng/ml, P=0.007), and average hospital stay (10.6 +/- 5.4, 12.6 +/- 4.7,14.5 +/- 6.5 days, P=0.001). The MACE rate at 30 days (3.5, 5.3, 15.5%, P=0.04) was reduced and LVEF (0.51 +/- 0.07, 0.50 +/- 0.07, 0.47 +/- 0.08, P=0.008) was higher in upstream and downstream groups than in controls. At 6-month follow-up, the MACE rate was not significantly different among groups (7.0, 8.8, 17.2%, P=0.17), but LVEF in upstream and downstream groups was significantly improved (0.59 +/- 0.06, 0.57 +/- 0.07, 0.54 +/- 0.07, P < 0.001). Subgroup analysis demonstrated a statistically significant difference between upstream and downstream groups in preprocedural TIMI grade 3 flow (P=0.003) and postprocedural corrected TIMI frame count (P=0.007), which resulted in a shortened hospital stay (P=0.04), reduction of MACE rate at 30-day and 6-month follow-up by 34 and 20%, respectively. Multivariate logistic analysis revealed that age more than 65 years [odds ratio (OR)=3.42, P < 0.01], tirofiban therapy (OR=0.56, P < 0.05) and LVEF less than 0.5 during hospitalization (OR=2.56, P < 0.01) were major independent predictors of MACE at 6-month clinical follow-up. No significant difference in hemorrhagic complications among three groups was noted (upstream: 10.5%, downstream: 12.3%, control: 6.9%, P=0.61). Conclusion This prospective study indicates that adjunctive tirofiban therapy for patients with STEMI who undergo primary PCI can significantly improve reperfusion level in the infarct area, clinical outcomes at 30-day and 6-month follow-up, especially with upstream tirofiban therapy, and is safe.