Tirofiban Group Research Articles

The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: The advance trial

ObjectivesWe sought to determine the safety and efficacy of high-dose bolus (HDB) tirofiban in high-risk patients undergoing percutaneous coronary intervention (PCI). BackgroundThe use of HDB tirofiban in the catheterization laboratory is controversial. In particular, in patients with acute coronary syndromes undergoing PCI, there is no evidence that tirofiban administered in the catheterization laboratory is superior to heparin alone. This finding probably reflects the suboptimal platelet inhibition when tirofiban is employed at RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) regimen. MethodsA total of 202 patients (mean age 69 ± 8 years; 137 males [68%]) undergoing high-risk PCI, pretreated with thienopyridines, were consecutively randomized to HDB tirofiban (25 μg/kg/3 min, and infusion of 0.15 μg/kg/min for 24 to 48 h) or placebo immediately before the procedure and then followed for a median time of 185 days (range 45 to 324 days) for the occurrence of the primary composite end point of death, myocardial infarction, target vessel revascularization (TVR), and bailout use of glycoprotein (GP) IIb/IIIa inhibitors. ResultsThe cumulative incidence of the primary end point was 35% and 20% in placebo and HDB tirofiban groups, respectively (hazard ratio 0.51, 95% confidence interval 0.29 to 0.88; p = 0.01). This difference was mainly due to the reduction of myocardial infarction and bailout use of GP IIb/IIIa inhibitors, with no significant effect on TVR or death. The safety profile did not differ between tirofiban and placebo. ConclusionsThe use of tirofiban, when administered at HDB, is safe and significantly reduces the incidence of ischemic/thrombotic complications during high-risk PCI.

Comparison in patients having primary coronary angioplasty of abciximab versus tirofiban on recovery of left ventricular function

In patients treated with primary coronary angioplasty, the use of abciximab improves microvascular perfusion and enhances the recovery of contractile function. This study compared the effects of the new dose regimen of tirofiban (25-μg/kg bolus followed by an 18-hour infusion at 0.15 μg/kg/min) on left ventricular function with those of abciximab in patients who underwent direct angioplasty. One hundred patients who underwent primary coronary angioplasty were randomized to receive a standard dose of abciximab or a large-dose bolus of tirofiban. The primary end point of the study was change in the infarct-zone wall motion score index between the initial and 30-day follow-up echocardiographic studies. The secondary end points were procedural evaluations before and after Thrombolysis In Myocardial Infarction (TIMI) grade flow, TIMI grade myocardial perfusion, and corrected TIMI frame count. Baseline global and regional ventricular functions were similar in the 2 treatment groups. After the procedure, a TIMI grade 3 flow was obtained in 86% of patients treated with abciximab and 88% of those receiving tirofiban (p = 1.0), whereas TIMI grade 3 myocardial perfusion was present in 70% and 76%, respectively (p = 0.65); corrected TIMI frame count was 22.5 ± 1.9 and 22.1 ± 2.5 (p = 0.37). After 30 days, we obtained 87 paired echocardiographic studies. The infarct-zone wall motion score index decreased from 2.20 ± 0.3 to 1.99 ± 0.2 in the abciximab group and from 2.18 ± 0.3 to 1.95 ± 0.3 in the tirofiban group (p = 0.67). Thus, in patients who had primary coronary angioplasty, abciximab, and the large-dose bolus of tirofiban showed similar effects on the initial angiographic results and 30-day recovery of left ventricular function.

Evaluation of Platelet Count and Function in Patients Administered Tirofiban or Eptifibatide Undergoing Percutaneous Coronary Intervention

Platelets play a pivotal role in the initial defense against insult to the vasculature, and they are critically important in the acute care setting of percutaneous coronary intervention (PCI). In this clinical environment, both platelet count and function are often affected. With the increasing use of adjunct antiplatelet agents, which include the antiglycoprotein IIb/IIIa (GPIIb/IIIa) agents, during PCI procedures it is now recognized that it may be important to monitor these agents to ensure that adverse side effects are minimized or avoided. However, traditional methods for monitoring platelet function are not suitable for acute care patient settings. The authors describe the temporal evaluation of platelet count and function of patients receiving an approved dosing regimen of eptifibatide and the RESTORE dosing regimen of tirofiban who are undergoing PCI using a practical and rapid whole-blood platelet function assay that has been developed for use in near-patient settings. The time to achieve maximal platelet inhibition took longer in those patients treated with tirofiban compared with those treated with eptifibatide. However, the recovery of platelet function was more rapid in the tirofiban group. This study demonstrates the utility of monitoring platelet count and function in PCI patients, the importance of which will be addressed in larger outcome studies.

Effects of Glycoprotein IIb/IIIa Receptor Inhibition with Tirofiban on Minor Myocardial Damage in Angiographically Successful Percutaneous Coronary Angioplasty

Aim: The aim of the study was to evaluate the effects of glycoprotein (GP) IIb/IIIa inhibition on minor myocardial injury characterized by cardiac troponin I (cTn-I) and cardiac troponin T (cTn-T) elevation after elective successful percutaneous coronary intervention (PCI). Methods: The study consisted of 119 consecutive patients scheduled for elective coronary balloon angioplasty with or without stent implantation. Sixty-three patients (mean age 58 ± 9.4 years) were randomized to receive standard therapy, including preprocedural aspirin, ticlopidine and intravenous heparin, and 56 patients (mean age 55 ± 9.6 years) were randomized to additionally receive intravenous tirofiban infusion. cTn-I, cTn-T and CK-MB were measured before and immediately after the procedure, and every 6 h for the first 24 h. A total of 128 stenoses were treated with PCI. Seventy of these lesions were in the standard therapy group and 58 in the tirofiban group. Results: The frequency of postprocedural abnormal cTn-I levels was significantly higher in the standard therapy group than that in the tirofiban group (37 vs. 16%; p = 0.017). Postprocedural cTn-T elevation occurred in 23% of patients in the standard therapy group and in 8% of patients in the tirofiban group (p = 0.037). The frequencies of CK-MB elevation higher than the upper limit of normal (ULN), and higher than 2 times the ULN were not significantly different between the standard therapy and tirofiban groups (12 vs. 4%, and 7 vs. 2%, respectively). Conclusions: GP IIb/IIIa inhibition may reduce the incidence of minor myocardial injury, which may also be a possible mechanism in reducing long-term cardiac events after PCI.

Safety of a high bolus dose of tirofiban in patients undergoing coronary stent placement.

To overcome the suboptimal platelet inhibition induced by tirofiban in the first hour after a percutaneous coronary intervention, a new regimen of 25 microg/kg bolus followed by an 18-hr infusion of 0.15 microg/kg/min has been proposed. The aim of this study was to compare the effects of this high bolus dose of tirofiban with those of abciximab on bleeding risk and 30-day clinical outcome in patients undergoing coronary stenting. We compared two cohorts of patients who underwent coronary stent placement between January 2000 and December 2002. In the first cohort, the only available IIb/IIIa receptor inhibitor was abciximab, which was given to 280 (34.9%) out of 802 stented patients; in the second cohort, tirofiban was administered to 274 (38.3%) out of 716 treated patients. The primary endpoints were the proportion of patients with major bleeding and the rate of site access complications; the 30-day incidence of major adverse cardiac events (MACE) was also assessed. After the procedure, the patients were given ticlopidine for 4 weeks and aspirin indefinitely. Major bleeding episodes were observed in four patients receiving abciximab and in none receiving tirofiban (1.4% vs. 0%; P = 0.12); the rates of site access complications were similar (3.6% vs. 3.3%; P = 0.96). The 30-day incidence of MACE was 7.1% in the abciximab group and 5.8% in the tirofiban group (P = 0.65). In patients undergoing coronary stenting, the high bolus dose of tirofiban is safe and not associated with an increased risk of major bleeding or site access complications in comparison with abciximab.

The Effect of Tirofiban on ST Segment Resolution in Patients With Non-ST Elevated Myocardial Infarction

ST segment resolution in ST elevated myocardial infarction has independent predictive value for congestive heart failure and death at 30 days. ST segment depression in unstable angina pectoris (UAP) and non-ST elevated myocardial infarction (NSTEMI) predicts high risk of MI and death and may discriminate patients likely to have greater benefit from aggressive antithrombotic and interventional therapy. This study assessed the effect of tirofiban added to conventional treatment on ST segment resolution in NSTEMI patients. Sixty-four patients were randomized to one of the two groups: 32 patients received conventional treatment while tirofiban was added in the second group of 32 patients. In the first group, 6 patients refused to participate further after giving initial informed consent while 1 patient in the tirofiban group dropped out. We had 26 patients (mean age, 59 years) in the conventional treatment group and 31 patients (mean age, 59 years) received also tirofiban. Tirofiban was administered by intravenous infusion over a 72 hour period. More than 50% regression of depression was considered to be ST segment resolution. The characteristics of the two groups were comparable (Table I). The ST segment resolution evolution did not differ at the 4th and 24th hours between the two groups. Significant differences occurred in the 72nd hour ECG (Table III). ST resolution was present in 67.9% of the tirofiban patients and in 32.1% of the conventional treatment group (P < 0.05). Tirofiban treatment was not associated with an increase in major bleeding even though there was a trend toward an increase in minor bleeding cases and did not influence the occurrence of refractory angina pectoris.

Effect of tirofiban on C-reactive protein in non-ST–elevation myocardial infarction

ObjectivesC-reactive protein (CRP) is a prototypic marker of inflammation. The effect of tirofiban on CRP levels in patients with non-ST–elevation myocardial infarction (NSTEMI) was investigated. MethodsThe present study was prospective and randomized. Patients with NSTEMI received aspirin, clopidogrel, statin, and unfractionated heparin. Patients with NSTEMI were enrolled into either the tirofiban + heparin group (group 1: n = 25) or the heparin group (group 2: n = 32). Levels of CRP were determined at baseline and after 48 and 72 hours. Heparin and tirofiban were discontinued after 48 hours. ResultsLevels CRP of were similar in two groups at baseline; they increased significantly at 48 hours and 72 hours in the control group but not in the tirofiban group. The differences on and after treatment were statistically significant. In group 1, CRP elevation was attenuated after tirofiban infusion compared with group 2. ConclusionsProducts of platelet activation may aid neutrophil accumulation and enhance inflammation. Activated leukocytes and platelets potentate each others' effects. Tirofiban strongly inhibits the platelet aggregation. The decreased platelet aggregation can suppress the inflammatory protein, chemokine, and adhesion molecule expression. After the tirofiban infusion, CRP elevation was atteunated in patients with NSTEMI.

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Effect of abciximab versus tirofiban on activated clotting time during percutaneous intervention and its relation to clinical outcomes—observations from the TARGET trial

Previous evidence suggests that the monoclonal antibody abciximab may have a more potent anticoagulant effect than small-molecule glycoprotein (GP) IIb/IIIa inhibitors. We prospectively reviewed collected heparin dose, activated clotting time (ACT), and corresponding clinical outcome data from The Do Tirofiban and ReoPro Give Similar Efficacy Outcome Trial (TARGET), a direct comparison of tirofiban versus abciximab in patients who underwent percutaneous intervention. Of the 4,809 patients enrolled in the trial, 3,739 patients (78%) had an ACT measured after the administration of GP IIb/IIIa and heparin (peak procedural ACT); this formed the population for the present study. Mean total heparin dose was 75 ± 32 and 76 ± 31 U/kg in the tirofiban and abciximab groups, respectively. The resultant mean peak ACTs were 296 ± 91 and 299 ± 89 seconds (p = 0.09). In a subset of patients with both baseline ACT (before any heparin or GP IIb/IIIa therapy) and peak procedural ACT measurements, the difference in ACT between these time points was 80 ± 97 vs 82 ± 101 seconds (p = 0.44) for the tirofiban and abciximab groups, respectively. After adjusting for patients’ weight, weight-adjusted heparin dose, and method of ACT measurement in a multiple linear regression analysis, the type of GP IIb/IIIa inhibitor was not predictive of the peak ACT (p = 0.24). When stratified by ACT quartile, no statistically significant difference in bleeding or ischemic end points between the tirofiban and abciximab cohorts was observed. In this large contemporary percutaneous coronary intervention trial, there was no observed difference in the anticoagulant effect of tirofiban and abciximab, as measured by the ACT, or in the incidence of bleeding or ischemic complications in each ACT quartile.

Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial)

ObjectivesThe Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release. BackgroundNo data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel. MethodsAfter bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h. ResultsA total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05). ConclusionsTroponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.

Bleeding Risk of Tirofiban, a Nonpeptide GPIIb/IIIa Platelet Receptor Antagonist in Progressive Stroke: An Open Pilot Study

Background:Glycoprotein (gp) IIb/IIIa-receptor antagonists are highly effective antiplatelet agents with proven efficacy in the treatment of acute coronary and experimental cerebral ischemia. In this study we examined the rate of hemorrhagic transformation and major bleedings in patients with acute stroke treated with tirofiban, a nonpeptide gpIIb/IIIa antagonist. Methods: Eighteen patients with progressively deteriorating acute ischemic stroke were treated with body-weight adjusted intravenous tirofiban for a mean period of 46 h and compared with a matched group of 17 acute ischemic clinically stable stroke patients. Cerebral hemorrhage was assessed by cranial imaging 6–10 days after symptom onset. Results: No major intracranial hemorrhage was observed in either group. Clinically asymptomatic hemorrhagic infarctions type I/II/III were detected in 4/2/0 controls and in 4/1/1 patients of the tirofiban group, respectively (OR = 0.92; 95% CI 0.4–2.5). Clinical outcome scores were not different in both groups (p = 0.18). Conclusions: Tirofiban was not associated with a significantly increased cerebral bleeding rate in acute ischemic stroke. Randomized multicenter studies are needed to further evaluate the safety and efficacy of tirofiban in the treatment of acute stroke.

Combination therapy with tirofiban and enoxaparin in acute coronary syndromes

Background: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. Materials and methods: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 μg/kg/min i.v.) for 48–108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) ( n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) ( n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. Results: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7±59.8 and 187.5±81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients ( P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 μM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. ≥30 min for tirofiban and unfractionated heparin ( P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. Interpretation: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.

Six-month angiographic and clinical follow-up of patients prospectively randomized to receive either tirofiban or placebo during angioplasty in the RESTORE trial

Objectives. This study sought to investigate the effects of tirofiban versus placebo on the incidence of adverse cardiac outcomes and coronary artery restenosis at 6 months.Background. Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platelet glycoprotein IIb/IIIa. In a recent clinical study, tirofiban reduced the incidence of adverse cardiovascular events at both 2 and 7 days after coronary angioplasty or directional coronary atherectomy. This reduction persisted but was no longer statistically significant at 30 days.Methods. The Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trial was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing balloon angioplasty or directional atherectomy within 72 h of presentation with either unstable angina pectoris or acute myocardial infarction. All patients received an initial bolus (10 μg/kg body weight over 3 min), followed by a 36-h infusion (0.15 μg/kg per min) of either tirofiban or placebo.Results. At 6 months the composite end point (either death from any cause, new myocardial infarction, bypass surgery for angioplasty failure or recurrent ischemia, repeat target vessel angioplasty or stent insertion for actual or threatened abrupt closure) occurred in 1,070 placebo group patients (27.1%) and 1,071 tirofiban group patients (24.1%, p = 0.11). Analysis of 6-month coronary arteriograms by means of quantitative coronary arteriography showed no significant difference between placebo- and tirofiban-treated patients in either the incidence of a ≥50% diameter stenosis (57% vs. 51%, p = NS), a loss of ≥50% of lumen diameter gained (50% vs. 50%, p = NS) or a loss of ≥0.72 mm of lumen diameter (44% vs. 42%, p = NS).Conclusions. The 3% absolute reduction in the incidence of the composite end point at 6 months (27.1% placebo vs. 24.1% tirofiban) was similar to that previously reported at 2 days (8.7% vs. 5.4%, p < 0.005), and there does not appear to be any late effect of tirofiban on clinical end points between day 2 and 6 months. Tirofiban did not reduce the incidence of restenosis at 6 months when defined in a number of ways.

Effects of Platelet Glycoprotein IIb/IIIa Blockade With Tirofiban on Adverse Cardiac Events in Patients With Unstable Angina or Acute Myocardial Infarction Undergoing Coronary Angioplasty

Background Adverse cardiovascular events associated with thrombotic occlusion occur in 4% to 12.8% of patients after coronary angioplasty. Recently, potent antiplatelet agents have been used to reduce those thrombotic complications. Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platelet glycoprotein (GP) IIb/IIIa that inhibits ex vivo platelet aggregation in response to a variety of agonists. Methods and Results The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, double-blind, placebo-controlled trial of tirofiban in patients undergoing coronary interventions (balloon angioplasty or directional atherectomy) within 72 hours of presentation with an acute coronary syndrome (unstable angina pectoris or acute myocardial infarction). The end points of the study were death from any cause, myocardial infarction, coronary bypass surgery due to angioplasty failure or recurrent ischemia, repeat target-vessel angioplasty for recurrent ischemia, and insertion of a stent due to actual or threatened abrupt closure of the dilated artery, and the primary end point was a composite representing the occurrence of any of these events. The prespecified primary hypothesis of the study was that tirofiban, administered as a bolus of 10 μg/kg over a 3-minute period and followed by a 36-hour infusion of 0.15 μg · kg −1 · min −1 , would result in a reduction in the 30-day composite end point compared with placebo. Patients (n=2139) who were already receiving treatment with aspirin and heparin were randomized to receive tirofiban or placebo. The primary composite end point at 30 days was reduced from 12.2% in the placebo group to 10.3% in the tirofiban group, a 16% relative reduction ( P =.160). However, 2 days after angioplasty, the tirofiban group had a 38% relative reduction in the composite end point ( P ≤.005), and at 7 days there was a 27% relative reduction (P=.022), largely because of a reduction in nonfatal myocardial infarction and the need for repeat angioplasty. When repeat angioplasty or coronary artery bypass surgery procedures were included in the composite only if performed on an urgent or emergency basis, the composite 30-day event rates were 10.5% for the placebo group and 8.0% for the tirofiban group, a relative reduction of 24% ( P =.052). Major bleeding, including transfusion, was not significantly different between the two groups (3.7% in the placebo group and 5.3% in the tirofiban group; P =.096). When the Thrombolysis In Myocardial Infarction (TIMI) criteria for major bleeding were used, the incidence was 2.1% in the placebo group compared with 2.4% in the tirofiban group ( P =.662). Thrombocytopenia was similar in the placebo and tirofiban groups (0.9% for the placebo group versus 1.1% for the tirofiban group; P =.709). Conclusions In patients undergoing coronary angioplasty for acute coronary syndromes, tirofiban protects against early adverse cardiac events related to thrombotic closure. At 30 days, however, the reduction in adverse cardiac events was no longer statistically significant. The bleeding observed with tirofiban was not statistically different from that observed with placebo.

Tirofiban provides “platelet anesthesia” during cardiopulmonary bypass in baboons

Objective: Tirofiban (Aggrastat) is a reversible, nonpeptide inhibitor of platelet glycoprotein II/IIIa receptors. We tested the hypothesis that tirofiban preserves platelet number and function and shortens postoperative bleeding times in baboons after cardiopulmonary bypass. Methods: Four groups were studied: control, n = 12; low-dose tirofiban (0.1 μg/kg per minute), n = 7; high-dose tirofiban (0.3 μg/kg per minute), n = 7; and bolus tirofiban (15 μg/kg) followed by 0.1 μg/kg per minute during cardiopulmonary bypass, n = 7. After heparin, animals were perfused for 60 minutes at 50 ml/kg per minute and 37° C with a bubble oxygenator, roller pump, and peripheral cannulation. Hemodynamics, platelet count, platelet aggregation to adenosine diphosphate, and release of β-thromboglobulin were measured before tirofiban infusion, before heparin, after heparin before bypass, after 5 and 55 minutes of bypass, after protamine, and 60 minutes after protamine. Template bleeding times were measured at the same times except during cardiopulmonary bypass and 120 and 180 minutes after protamine administration. Platelet glycoprotein IIIa antigen was measured in Triton X-100 washes (Sigma Chemical Company) of the perfusion circuit after bypass. Results: High-dose tirofiban completely prevents platelet loss during cardiopulmonary bypass. β-Thromboglobulin release and sensitivity to adenosine diphosphate are significantly less than control at the end of bypass in all tirofiban groups. Template bleeding times return to preoperative values in both the low- and high-dose tirofiban groups 180 minutes after protamine administration and are significantly less than control bleeding times at both 120 and 180 minutes after protamine. Surface glycoprotein IIIa antigen does not significantly differ between groups. Conclusion: High-dose tirofiban completely preserves platelet number and improves platelet function during cardiopulmonary bypass in baboons and significantly accelerates restoration of normal template bleeding times after bypass(J Thorac Cardiovasc Surg 1997;113:182-93)