Tirofiban In Patients Research Articles

Long-Term Clinical Outcome Based on Aspirin and Clopidogrel Responsiveness Status After Elective Percutaneous Coronary Intervention: A 3T/2R (Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel) Trial Substudy

The purpose of this study was to investigate the long-term outcome after elective percutaneous coronary intervention in low-risk patients screened for aspirin and/or clopidogrel responsiveness in the 3T/2R (Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel) trial. The impact of aspirin and/or clopidogrel poor response on long-term outcome is debated. Aspirin and clopidogrel response was measured with the VerifyNow system aspirin and P2Y12 assays. After percutaneous coronary intervention (PCI), death, stroke, and myocardial infarction were assessed up to 1 year. Overall, 1,277 patients were screened, and 826 (65%) were treated with PCI. In all, 124 patients were found to be aspirin poor responders, and there were 179 clopidogrel poor responders (totally, 278 poor responders). The 1-year end point was significantly higher in poor responders as compared to full responders (15.8% vs. 8.6%, p=0.002), which is principally due to more myocardial infarction occurrence. At multivariable analysis, clopidogrel poor response emerged as an independent predictor (hazard ratio: 1.15, 95% confidence interval: 1.03 to 1.28). Receiver-operator characteristic analysis identifies≤23 of percentage of platelet inhibition and ≥208 of P2Y12 reactivity units as optimal cut offs to predict 1-year end point. Excluding periprocedural events, also peri-PCI myocardial infarction, which is strongly related to aspirin/clopidogrel poor response, was an independent predictor (hazard ratio: 1.25, 95% confidence interval: 1.14 to 1.37). Glycoprotein IIb/IIIa inhibitor administration reduces this risk in poor responders (21.2% vs. 34.7%, p=0.02), but not in full responders (6.3% vs. 6.5%, p=0.8). Poor response to clopidogrel is an independent predictor of periprocedural myocardial infarction and worse 1-year outcome in low-risk patients undergoing PCI, whereas poor response to aspirin failed to predict a worse outcome. Contrary to what was observed in poor responders, glycoprotein IIb/IIa inhibitor therapy failed to provide a benefit in aspirin and/or clopidogrel full responders.

E0329 Safety and feasibility of tirofiban in elective PCI of complex coronary artery disease

ObjectivesTo observe the effect of tirofiban on cardiac markers, platelet aggregation rate and major adverse cardiac events (MACE) in patients with complex coronary artery disease undergoing elective PCI and discuss...

E0485 Clinic study of domestic tirofiban on TIMI Flow during facilitated PCI

ObjectiveTo assess Thrombolysis In Myocardial Infarction (TIMI) flow of the nation-produced tirofiban in patients with ST-segment elevation myocardial infarction (STEMI) during primary Percutaneous Coronary Intervention (PCI).Methods120 patients with STEMI during...

E0638 Clinical effects and safety of delayed PCI combined with tirofiban in patients with acute myocardial infarction

ObjectiveTo explore the clinical effects and safety of the delayed PCI combined with tirofiban compared with selective PCI in acute myocardial infarction (AMI) patients, so as to perform an earlier...

Clinical Observation of primary percutaneous coronary intervention combined with tirofiban therapy in treatment patients with acute ST-segment elevation myocardial infarction

Objective This study was conducted to investigate the clinical outcomes and safety of primary percutaneous coronary intervention(PCI) combined with tirofiban therapy in patients with acute ST segment elevation myocardial infarction(STEMI). Methods Seventy-one consecutive patients with acute STEMI were divided by random number table to primary PCI combined with tirofiban therapy group(Tirofiban group,25 cases) and primary PCI treatment alone group(Control group,46 cases). Left ventricular ejection fraction(LVEF) and major adverse cardiac events rates(MACE) during hospitalization period and at 30 days discharge and 180 days after discharge were compared between the two groups. Results TIMI grade flow was significantly different between the tirofiban group and control group after surgery. The LVEF and MACE were significantly different between two groups during hospitalization period and at 30 days after discharge. The MACE at 180 days followup was relatively reduced and LVEF was relatively improved in tirofiban group, but there was not significantly different. Conclusion Adjunctive therapy with tirofiban for patients with acute STEMI who underwent primary PCI was safe and effective. Key words: Myocardial infarction; Angioplasty,transluminal,percutaneous coronary; Tirofiban

Effect of Early, Pre-Hospital Initiation of High Bolus Dose Tirofiban in Patients With ST-Segment Elevation Myocardial Infarction on Short- and Long-Term Clinical Outcome

The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear. The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up. During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed. Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297).

Prehospital high-dose tirofiban in patients undergoing primary percutaneous intervention. The AGIR-2 study

Compared with administration in the catheterization laboratory, early treatment with glycoprotein IIb/IIIa inhibitors provides benefits to patients with ST-segment elevation myocardial infarction who undergo primary percutaneous intervention. Whether this benefit is maintained on top of a 600 mg loading dose of clopidogrel is unknown. In a multicentre, controlled, randomized study, 320 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention received a high-dose bolus of tirofiban given either in the ambulance (prehospital group) or in the catheterization laboratory. The primary endpoint was a TIMI flow grade 2-3 of the infarct-related vessel at initial angiography. Secondary endpoints included ST-segment resolution 1h after percutaneous coronary intervention and peak serum troponin I concentration. Tirofiban was administered 48 (95% confidence interval 21.4-75.0) min earlier in the prehospital group. At initial angiography, the combined incidence of TIMI 2-3 flow was 39.7% in the catheterization-laboratory group and 44.2% in the prehospital group (p=0.45). No difference was found on postpercutaneous intervention angiography or peak troponin concentration. Complete ST-segment resolution 60 min after the start of intervention was 55.4% in the catheterization-laboratory group and 52.6% in the prehospital group (p=0.32). Prehospital initiation of high-dose bolus tirofiban did not improve significantly initial TIMI 2 or 3 flow of the infarct-related artery or complete ST-segment resolution after coronary intervention compared with initiation of tirofiban in the catheterization laboratory (NCT00538317).

Response to Letter Regarding Article, “Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study”

Response to Letter Regarding Article, “Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study”

Tirofiban for myocardial infarction

Importance of the field: Inhibition of platelet aggregation plays a key role in treatment of coronary artery disease.Areas covered in this review: Studies on the effects of tirofiban in patients with either ST elevation or non-ST elevation myocardial infarction are reviewed.What the reader will gain: Tirofiban is a small-molecule glycoprotein IIb/IIIa receptor inhibitor. If discontinued, the action of tirofiban is faster reversed as abciximab. The dose varied between low (bolus of 0.4 μg/kg administered over 30 min followed by an infusion of 0.10 μg/kg/min), intermediate (bolus of 10 μg/kg administered over 3 min followed by an infusion of 0.15 μg/kg/min) and high (bolus of 25 μg/kg administered over 3 min followed by an infusion of 0.15 μg/kg/min). The high-dose administration especially may be beneficial in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). There is no indication for tirofiban in patients treated with thrombolysis. Patients with non-ST elevation myocardial infarction requiring PCI are most likely to benefit from tirofiban if they have ongoing ischemia and/or dynamic ECG changes. The risk of serious bleeding with tirofiban is low and there is a very low risk of thrombocytopenia.Take home message: Use of tirofiban for myocardial infarction is effective and has an acceptable safety profile.

Letter by Doraiswamy Regarding Article, “Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study”

To the Editor: Valgimigli et al1 conducted an interesting prospective study on the effect of tirofiban in poor responders to aspirin, clopidogrel, or both undergoing elective coronary intervention. Although the reasons for recruiting low-risk patients in the study are explained,2 this study cannot be incorporated into commonly encountered advanced cardiac patients. Certain additional details and controversies need to be addressed. I find that the placebo group …

Treatment of Progressive Stroke with Tirofiban – Experience in 35 Patients

Background: In an open pilot study, we studied the safety and efficacy of treatment with the nonpeptide glycoprotein IIb/IIIa antagonist tirofiban in patients with progressive ischemic stroke. The rationale for the use of tirofiban in progressive stroke is the effect on vessel patency and microcircu lation. Methods: Patients with acute ischemic stroke and progression of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) in the first 96 h after stroke onset were treated with intravenous tirofiban. Serial NIHSS measurements and intra- and extracerebral bleeding complications were recorded. Results: Progressive stroke was observed in 35 patients with a mean progression of 5.4 (SD 4.1) points on the NIHSS. No severe bleeding complications occurred during tirofiban treatment. Analysis of variance revealed a significant interaction between stroke etiology (small-vessel vs. large-vessel occlusion) and NIHSS during treatment with tirofiban: patients with small-vessel occlusion showed significant improvement, while patients with large-vessel occlusion did not. The mean NIHSS improvement after tirofiban infusion was 3.4 (SD 3.4) for small-vessel occlusion versus 0.8 (SD 4.2) for large-vessel occlusion (p = 0.048). Conclusion: Treatment with tirofiban was well tolerated in patients with progressive stroke. However, only patients with small-vessel occlusion recovered significantly during infusion of tirofiban. The effect of tirofiban in progressive stroke and different subgroups of stroke deserves to be studied in a randomized controlled trial.

In Vitro Inhibition of Platelet Aggregation in Response to Increasing Concentrations of Tirofiban in Patients with Significant Renal Insufficiency

Patients with impaired renal function are a growing subset at higher risk for cardiovascular complications due to vasculopathic state, inducing accelerated atherosclerosis and arteriosclerosis. These patients are at increased risk for complications after coronary interventions, especially major bleeding events. As a result, this at-risk population of patients has not been well studied in most of the major clinical trials evaluating coronary interventions. Of particular interest is the optimal dosing of glycoprotein IIb-IIIa inhibitors in the setting of acute myocardial infarction. In this study, we attempted to find the in vitro concentration of tirofiban required to inhibit platelet aggregation to <10% in patients with moderate to severe renal insufficiency. A total of 21 patients were divided into two groups based on estimated creatinine clearance (group 1 <46ml/min; group 2 >46ml/min). Platelet-rich plasma from each subject was then incubated in vitro with increasing concentrations of tirofiban (25, 37.5, and 50ng/ml), and light transmission aggregometry assay was used to assess the degree of platelet aggregation in response to adenosine diphosphate (ADP). Patients in group 1 had a baseline platelet aggregation of 45%, which decreased to 10% at a 25.0ng/ml concentration of tirofiban; the effect was enhanced to a platelet aggregation of <5% at higher doses. In contrast, subjects in group 2 with creatinine clearance >or=46ml/min had an average platelet aggregation inhibition of 12% with 50ng/ml of tirofiban.We found a significant decrease in platelet aggregation in group 2 at 25, 37.5, and 50ng/ml of tirofiban (p<0.05) in comparison with group 1. Our data indicate that patients with moderate to severe renal dysfunction suppress their platelet aggregation to <10% with 25ng/ml of tirofiban, one-third of the standard effective dose for patients with normal renal function.We suggest further clinical trials to define an objective means to calculate proper renal dosing of glycoprotein IIb-IIIa inhibitors in these patients to prevent potentially fatal complication of major hemorrhagic events.

Safety and efficacy of firebird drug-eluting stent combination tirofiban in patients with acute coronary syndrome

To evaluate the safety and efficacy of Firebird drug-eluting stent (DES) combining Tirofiban and Cypher DES combining Tirofiban in patients with acute coronary syndrome (ACS). 323 ACS patients were divided into 2 general conditions-matched groups: Firebird group (n = 161) undergoing Firebird DES implantation and Tirofiban intravenous injection 10 microg x kg(-1) within 3 minutes followed by Tirofiban 0.15 microg x kg(-1) x min(-1) intravenous maintenance infusion with micro pump for 36 hours, and Cypher group (n = 162) undergoing Cypher DES implantation and Tirofiban. The safety was observed instantly and 36 h after the implantation. The patients were followed up for 30 d. Some patients in the Firebird group underwent coronary angiography and intravascular ultrasound because of angina and part of target vessels underwent revascularization. There were no significant differences between the 2 groups in ejection fraction target coronary lesion type, blood platelet count, HB and HCT before treatment. The success rates of operation were both 100% in these 2 groups. No complication occurred in both groups. There were not significant differences in the blood platelet count, hemoglobin, hematocrit, acute stent thrombosis rate (1.2% vs 1.2%), acute myocardial infarction rate (1.3% vs 1.3%), target vessel revascularization rate (0.6% vs 1.3%), and rehospitalization rate (1.3% vs 0.7%) (all P > 0.05). 30 d no in-stent restenosis was found by angiographic and intravascular ultrasound follow-up in the Firebird group. Firebird DES combining Tirofiban and Cypher DES combining Tirofiban are both safe and effective in treating ACS.

Mechanical reperfusion: treat well, treat on time too

The search for evidence in primary percutaneous coronary intervention (pPCI) has not been straightforward, and has typically consisted of sequences of studies with new, confirmatory, or contradictory information that sometimes bring hope but too often confusion. Most major innovations have gone through this period of doubt, and antiplatelet therapy is no exception. Paradoxically we might have reached the point when new studies, presented or published in the past few months and the study reported in today's Lancet by Arnoud van't Hof and colleagues (the On-TIME 2 trial), 1 van't Hof AWJ ten Berg J Heestermans T et al. on behalf of the Ongoing Tirofiban In Myocardial infarction Evaluation (On-TIME) 2 study groupPrehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet. 2008; 372: 537-546 Summary Full Text Full Text PDF PubMed Scopus (391) Google Scholar have succinctly illuminated the path towards evidence. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trialOur finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI. Full-Text PDF

Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial

The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre. We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297. 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36). Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.

Comparison of efficacy and safety of native eptifibatide vs. tirofiban in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Objective To compare clinical outcomes and safety of eptifibatide or tirofiban in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods Thirty-six patients with ACS (unstable angina/non-ST-segment elevation myocardial infarction, UA/NSTEMI) who underwent PCI were randomly divided into two groups to receive eptifibatide or tirofiban treatment. Eptifibatide or tirofiban was predominantly initiated in the catheter laboratory before the intervention. In-hospital and 30-day MACE outcomes; bleeding as well as platelet counting were investigated in those two groups. Results No in-hospital and 30-day MACE event occurred in the two groups. The number of ischemia leads after treatment reduced compared to that before PCI in the two groups. There was improvement in the number of ischemia leads for 24 h after administration in the tirofiban group than those in eptifibatide group (4.21 ± 2.46 vs. 3.89 ± 3.31, P =0.03). The two groups showed no incidence of massive bleeding. Minor bleeding rates were 16.7% and 22.2% in the two groups respectively. Conclusion Eptifibatide as an adjunct to PCI may further decrease the incidence of ischemia event in patients with ACS and improve the safety, but its long-term efficacy and side effects need further observation.

Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel (3T/2R). Rationale for the Study and Protocol Design

To assess whether glycoprotein IIb/IIIa inhibition using tirofiban in low risk patients undergoing percutaneous coronary intervention (PCI) may reduce the risk of periprocedural myocardial infarction compared to standard care in poor responders to aspirin and/or clopidogrel. We will enroll patients at ten European sites or more to participate in the Tailoring Treatment with Tirofiban in patients showing Resistance to aspirin and/or Resistance to clopidogrel (3T/2R) study with a pre-specified sample size of 240 patients out of 1,100 or more who will undergo screening. The primary outcome measure is troponin I or T elevation ratio at least three times the upper limit of normal within 48 h after completion of the PCI. The results of 3T/2R study will evaluate whether tailored intensification of anti-platelet treatment based on poor individual response to oral anti-platelet agents may modulate the risk of periprocedural myocardial infarction during PCI. Our findings attempt at unraveling a new era of individualized anti-platelet treatment through the use of point-of-care assessment.

Effect of Intracoronary Tirofiban in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome

To investigate the efficacy of intracoronary tirofiban during primary percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS). The 118 patients aged 70 years and above (average age 75+/-2) were divided into study (n = 58, intracoronary bolus tirofiban) and control (n = 57, intravenous tirofiban) groups. The culprit vessels were targeted with primary PCI in all patients. Compared with the control group, the study group showed better Thrombolysis In Myocardial Infarction (TIMI) flow grades and TIMI myocardial perfusion grades (TMPG) immediately after PCI (p = 0.016 and 0.026, respectively). The 14-day composite major adverse cardiac events rate was lower in the study group (3.5% vs 17.5%, p = 0.030), but was similar between the 2 groups at 30 days following PCI (7.0% vs 1.7%, p = 0.350). The left ventricular ejection fraction in the study group was higher than in the control group 30 days following PCI (67.4+/-6.2% vs 60.7+/-4.6%, p = 0.033). The 14-day bleeding complication (p = 0.201) and platelet reduction rates (p = 0.984) were similar between the 2 groups. In patients with ACS undergoing primary PCI, intracoronary bolus administration of tirofiban is superior to intravenous bolus injection for improving coronary flow, myocardial perfusion and short-term clinical outcomes.

Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial.

In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T(0)), immediately after (T(1)), 30 minutes (T(2)), 60 minutes (T(3)) and 120 minutes (T(4)) after primary PCI. The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04). Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T(1) (p=0.006) and T(4) (p<0.0001). The administration of high-dose tirofiban resulted in a significantly higher inhibition of platelet aggregation compared with the currently recommended dose of abciximab. Large clinical trials are needed to assess whether this laboratory superiority of high-dose tirofiban translates into higher clinical efficacy. (Neth Heart J 2007;15:375-81.).

Routine upstream versus selective down stream use of tirofiban in non-ST elevation myocardial infarction patients scheduled for early invasive therapy; a randomized comparison

Despite their proven beneficial effects and inclusion in the guidelines, glycoprotein (GP) IIb/IIIA blockers are underused in daily practice in patients with non ST-segment elevation acute coronary syndrome (NSTE ACS). This study combines the data from two randomized controlled trials, comparing routine upstream versus selective down stream use of tirofiban in patients with NSTE ACS. Inclusion criteria for both studies (ELISA-1 and 2) were angina pectoris, with ST depression >1 mm and or a positive cardiac biomarkers. All patients were scheduled for coronary angiography. The primary and secondary end points for both studies were enzymatic infarct size (LDHQ48) and initial TIMI flow of the culprit lesion respectively. From August 2000 to January 2005, 273 patients were randomized to routine upstream tirofiban and 275 patients to selective down stream use of tirofiban. Selective down stream tirofiban was used in 55 patients (20%). Patients in the upstream group more often had a patent culprit lesion (65% vs. 50%, P=0.003) and a significantly smaller enzymatic infarct size, LDHQ48 median (25-75%): 125 (55-309) vs. 189 (68-504) IU/l, P=0.006 as compared to the selective down stream group. Subgroup analysis showed that routine upstream tirofiban was particularly effective in males, patients with a positive troponin on admission and in those not pretreated with clopidogrel. Routine upstream GP IIb/IIIa is mainly effective in patients with elevated troponin on admission and those not pretreated with clopidogrel. Large scale randomized trials are needed to evaluate the effect of GP IIb/IIIa blockers on top of clopidogrel pretreatment on major adverse cardiac events.