Abstract： Background For patients with moderate to high-risk acute coronary syndromes(ACS)who undergo early,invasive treatment strategies,current guidelines recommend the usage of glycoprotein(GP)lib/Illa inhibitors as an upstream treatment for a coronary care unit or as an downstream provisional treatment for selected patients who are undergoing percutaneous coronary intervention(PCI).The relative advantage of either strategy is unknown.The purpose of this study was to evaluate the effects of upstream tirofiban versus the effects of downstream tirofiban on myocardial damage and 180-day major adverse cardiovascular events(MACE)after PCI in high-risk non-ST-segment elevation ACS (NSTE-ACS)undergoing PCI.Methods From July 2006 to July 2007,160 high-risk NSTE-ACS undergoing PCI were randomized to receive upstream (within 4-6 hours before coronary angiography)tirofiban or downstream(the guidewire crossing the lesion)tirofiban,to evaluate the extent of myocardial damage after PCI by quantitatively and qualitatively analyzing the value of cardiac troponin I(cTnl)as well as MB isoenzyme of creatine kinase(CK-MB)before and after PCI.The incidences of 24-hour,3-day,7-day,30-day and 180-day MACE after PCI were followed up and the rates of bleeding complications and thrombocytopenia during tirofiban administration were recorded.Results The peak release and cumulative release of cTnl levels within 48 hours after PCI were significantly lower with upstream tirefiban than downstream tirofiban(0.45 vs 0.63 and 0.32 vs 0.43,respectively;P＜0.05).Post-procedural cTnl elevation within 48 hours was significantly less frequent among patients who received the upstream tirofiban than those who received the downstream tirefiban(66.3%vs 87.5%,P＜0.05).The peak and cumulative release of CK-MB levels as well as post-procedural CK-MB elevation within 48 hours after PCI were not significantly different between the two groups (16 vs 14,5 vs 3 and 26.3%vs 36.3%,respectively;P＞0.05).The incidences of 24-hour,3-day,and 7-day MACE after PCI were the same between the two groups(0 vs 0,0 vs 0 and 1.25%vs 1.25%,respectively).Although the incidences of 30-day and 180-day MACE after PCI were not statisticially different between the two groups,the incidences were consistently lower with upstream tirofiban(3.75%vs 6.25%and 12.99%vs 16.67%;P＞0.05).Aging(OR=1.164,P＜0.001),hypertension(OR=4.165,P=0.037)and type 2 diabetes(OR=13.628,P＜0.001)were independent risk factors of MACE.The timing of administrating the tirofiban(OR=2.416,P=0.153)plays an extensive role in the incidence of MACE.The incidences of major and minor bleeding complications as well as mild thrombocytopenia during the administration of tirofiban were similar between the two groups(2.50%vs 1.25%,1.25%vs 1.25%and 1.25%vs 1.25%,respectively;P＞0.05).Conclusions Based on the pretreatment with aspirin and clopidogrel,upstream tirofiban was associated with attenuated minor myocardial damage and the tendency of reducing incidences of 180-day MACE after PCI among high-risk NSTE-ACS patients undergoing PCI.Aging,hypertension and type 2 diabetes were independent risk factors of MACE in high-risk NSTE-ACS patients undergoing PCI associated with tirofiban.