The Clinical Research Of The Timing Of Tirofiban For High-Risk Non-ST-segment Elevation Acute Coronary Syndrome Treated With Percutaneous Coronary Intervention

ObjectivePlatelet membrane glycoprotein IIb/IIIa receptor antagonist tirofiban can improve clinical outcomes of high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing percutaneous coronary intervention (PCI). The purpose of this study was to evaluate which therapeutic strategy was better on reinforced anti-platelet treatment as well as reduced the incidence of short-term and intermediate-term major adverse cardiovascular event (MACE) after PCI, comparing upstream tirofiban versus downstream tirofiban in high-risk NSTE-ACS patients undergoing PCI.Methods160 high-risk NSTE-ACS patients (from 25 to 80 years-old)undergoing PCI within 48h of admission were randomized to receive upstream tirofiban and downstream tirofiban in a prospective placebo-controlled trial.High-risk NSTE-ACS was including: non-ST-segment elevation acute myocardial infarction, unstable angina associated with at least one of the following findings: (1) repeated angina at rest within 48h, (2) ischemic electrocardio-graphic changes consisting of ST depression≥0.1mV or transient(<20min) ST elevation≥0.1mV, (3) the history of prior PCI within 6 months, (4) known high-risk coronary lesions through coronary angiography, including left main disease, three-vessel disease, bifurcation disease, thrombotic disease and slowly flowing disease.Patients were randomized to receive upstream tirofiban (group1, within 4-6h before coronary angiography) and downstream tirofiban (group2, the guidewire crosses the coronary lesion). To observe the platelet function through detecting platelet aggregation inhibition after admission, before coronary angiography and after PCI. To compare the coronary angiography features through observing the Thrombolysis In Myocardial Infarction(TIMI)flow grade and the TIMI myocardial perfusion grade(TMPG) of target artery before and after PCI . To evaluate the extent of myocardial damage after PCI by quantitatively and qualitatively analyzing the value of cardiac troponin I (cTnI) as well as MB isoenzyme of creatine kinase (CK-MB) before and after PCI. Follow-up the incidence of 24h, three-day, seven-day, thirty-day and one hundred and eighty-day MACE after PCI. Univariate and multivariate analyses were conducted with logistic regression. To record the incidence of bleeding complications and thrombocytopenia from the beginning of administrating tirofiban to 24h after discontinuation.Results1. The extent of platelet aggregation inhibition after administered tirofiban was significantly better in the two groups (P<0.05). The extent of platelet aggregation inhibition at 24h after admission as well as 6, 24 and 48h after PCI were not statistically significant between the two groups (P>0.05). The extent of platelet aggregation inhibition before coronary angiography was significantly better with group1 (8% vs. 42%, P<0.05).2. The TIMI flow grade 2-3 and TMPG 2-3 perfusion were significantly more frequent with group1 compared with group2 before PCI(81% vs. 62% and 62% vs. 36%, respectively; P<0.05). The TIMI flow grade 3 was similar between the two groups after PCI (99% vs.98%, P>0.05), but group1 was also associated with a significantly better TMPG 2-3 perfusion (89% vs. 64%, P<0.05).3. The peak and cumulative release of cTnI levels within 48h after PCI were significantly lower with group1 than group2 (0.45 vs. 0.63 and 0.32 vs. 0.43, respectively; P<0.05). Post-procedural cTnI elevation within 48h was significantly less frequent among patients in the group1 compared with group2 (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 48h after PCI were not statistically significant between the two groups (16 vs. 14 , 5 vs. 3 and 26.3% vs. 36.3%, respectively; P>0.05).4. One hundred and eighty-day follow-up was available in 155(96.8%) of patients. The incidence of 24h, three-day, and seven-day MACE after PCI were same between the two groups(0% vs. 0%, 0% vs. 0% and 1.25% vs. 1.25%, respectively). The incidence of thirty-day and one hundred and eighty-day MACE after PCI were lower with group1 but were not statistically significant between the two groups(3.75% vs. 6.25% and 12.99% vs. 16.67%, respectively; P>0.05). The survival rate of one hundred and eighty-day non-MACE between the two groups respectively were 87% and 83.7% (P>0.05). Aging, hypertension and 2-type diabetes were independent risk factors of MACE. The choice of administrating tirofiban plays a extent role in the incidence of MACE.5. The incidences of major and minor bleeding complications as well as mild thrombocytopenia during administrating tirofiban were similar between the two groups (2.5%vs. 1.25%, 1.25%vs. 1.25% and 1.25%vs. 1.25%, respectively; P>0.05).Conclusion1. Based on pretreatment with aspirin and clopidogrel, upstream tirofiban are associated with the tendency of reduced the incidence of MACE after PCI among high-risk NSTE-ACS patients undergoing PCI. Aging, hypertension and 2-type diabetes were independent risk factors of MACE in high-risk NSTE-ACS patients undergoing PCI associated with tirofiban.2. Among high-risk NSTE-ACS patients treated with PCI, upstream tirofiban are associated with early reinforced anti-platelet treatment , improved target artery patency before PCI and corresponding myocardial perfusion before and after PCI , as well as attenuated minor myocardial damage.3. Tirofiban is safe.