Efficacy Of Tirofiban Research Articles

Clinical efficacy of tirofiban combined with Solitaire stent in the treatment of acute ischemic stroke

Clinical efficacy of tirofiban combined with Solitaire stent in the treatment of acute ischemic stroke

Safety and Efficacy of Tirofiban in Stent-Assisted Coil Embolization of Intracranial Aneurysms

Thromboembolic complications are a major concern in stent-assisted coiling of intracranial aneurysms that may be prevented with adequate antiplatelet therapy. To assess the safety and efficacy of tirofiban in stent-assisted coiling. Two protocols were used. In the initial protocol, tirofiban was administered intravenously as a 0.4 μg/kg per min bolus for 30 minutes followed by 0.10 μg·kg min maintenance infusion. The revised protocol consisted of a 0.10 μg·kg min maintenance infusion alone. Sixty-seven patients received tirofiban, 16 under the initial protocol and 51 under the revised protocol. Thirty (44.8%) patients had sustained a subarachnoid hemorrhage (SAH). Tirofiban infusion was initiated after thromboembolic events in 9 (13.4%) patients and prophylactically in 58 (86.6%). Four (6.0%) intracranial hemorrhages were noted. Three (18.8%) intracranial hemorrhages occurred with the initial protocol in patients treated electively and were fatal in 2 (66.7%) cases. The only complication (1.9%) under the revised protocol was a subclinical worsening of the computed tomographic appearance of an SAH. There was no tirofiban-related morbidity or deaths with the revised protocol. Of 9 patients that received tirofiban as a rescue treatment, 7 (77.8%) had complete and 2 (22.2%) had partial arterial recanalization. No thromboembolic events occurred in patients receiving prophylactic tirofiban. A bolus followed by a maintenance dose of tirofiban appears to have a high risk of cerebral hemorrhage. A maintenance infusion without an initial bolus, however, has an exceedingly low risk of hemorrhage and appears to be very safe and effective, even in the setting of SAH.

Treatment with tirofiban for acute coronary syndrome (ACS): a systematic review and network analysis

Objective:To assess the efficacy of tirofiban in comparison to usual care or other GPIIb/IIIa antagonists (eptifibatide and abciximab). Results were analysed by drug administration with planned percutaneous coronary intervention (PCI) or as medical management without planned PCI, and separately for STEMI or NSTE ACS patients.Research design and methods:A systematic review was performed of randomized controlled trials of tirofiban, abciximab, eptifibatide or usual care given to patients with acute coronary syndrome. Nine databases were searched up to March 2010. Pair-wise meta-analysis was used to combine all available direct comparisons; indirect comparisons and network analysis were performed when this was not possible. The primary outcome was MACE (major adverse cardiac event).Results:The search yielded 8, 119 records and 50 trials were included (total number of patients = 52,958). Compared to usual care, high and medium-dose tirofiban (25 and 10 µg/kg/min) administered with planned PCI reduced MACE at 30 days for patients with STEMI (RR 0.67, 95% CI 0.45, 0.99; RR 0.28, 95% CI 0.10, 0.80), but was not effective as a medical management. Medium-dose tirofiban (10 µg/kg/min) administered with planned PCI or low dose (0.4 µg/kg/min) as medical management reduced the risk of MACE for patients with NSTE ACS (RR 0.39, 95% CI 0.21, 0.75; RR 0.58, 95% CI 0.41, 0.83) in comparison to usual care, but at the expense of increased thrombocytopenia (RR 3.26, 95% CI 1.31, 8.13). Evidence from RCTs and network analysis indicated tirofiban and abciximab were equally effective and safe. Comparing tirofiban and eptifibatide treatment by indirect and network analysis produced inconclusive results.Conclusions:Tirofiban was more effective than usual care for STEMI and NSTE ACS patients receiving planned PCI, and NSTE ACS patients receiving medical management. Tirofiban and abciximab were equally effective. Comparisons of tirofiban and eptifibatide were inconclusive.

Tirofiban versus abciximab: tirofiban is administered at suboptimal dosages when evaluated in an arterial thrombosis model in non-human primates

To prevent thrombosis in high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention for re-vascularisation, concomitant administration of a glycoprotein IIb/IIIa inhibitor, such as abciximab, tirofiban or eptifibatide, is recommended. Abciximab and eptifibatide are mostly preferred over tirofiban, which is less effective in preventing ischaemic events. We compared the efficacy and bleeding potential of escalating doses of tirofiban and abciximab in non-human primates. The efficacy of tirofiban and abciximab in inhibiting cyclic flow reductions (CFRs) was tested in a high shear arterial thrombosis model. Bleeding was evaluated with the template bleeding time and an incision bleeding model. Abciximab completely inhibited arterial thrombosis after injection of its therapeutic bolus dose. With tirofiban, a dose three times higher than the recommended therapeutic dose caused weak inhibition characterised by a return of CFRs after re-injury. At nine times the recommended therapeutic dose, complete inhibition was observed, and the efficacy of tirofiban was comparable to abciximab at its therapeutic bolus dose. Blood loss was less than with abciximab at its effective dose. In this model, tirofiban compared favourably with abciximab, although only at a dose of 3-9 times the therapeutic dose, and caused less bleeding than abciximab.

Safety and Efficacy of Tirofiban as an Adjunctive Therapy for Patients with St-Elevation Myocardial Infarction: A Comparison Versus Placebo and Abciximab

Tirofiban is a nonpeptide tyrosine derivative that together with eptifibatide (both small molecules) and abciximam belongs to the group of glycoprotein IIb/IIIa inhibitors. Though similar to abciximab in that it has a high affinity for the GP IIbIIIa inhibitor receptor, tirofiban dissociates from it much faster tan abciximab, what makes its action reversible in a few hours. Initially used upstream for treatment of patients with non ST-elevation acute coronary síndromes, recent evidence has shown its role as adjuntive therapy in patients with ST-elevation acute myocardial infarction treated with primary angioplasty when used at a higher dose. In this article, we performed a thorough and systematic review of randomized trials comparing tirofiban versus pacebo and tirofiban versus abciximab when used in this subset of patients. All these studies showed tirofiban to be a well tolerated and effective IIbIIIa inhibitor. When compared with placebo, tirofiban was associated with a significant reduction in mortality and myocardial infarction at one month, with a higher risk of minor bleeding in the follow-up. When compared with abciximab, tirofiban showed no difference in mortality and a tendency to higher rate of the composite of death and myocardial infarction in the short term follow-up that disappeared when only studies with high-dose tirofiban were considered. On the basis of the high-dose regimen, tirofiban may be considered useful in the management of patients with ST-elevation myocardial infarction who undergo primary angioplasty.

Efficacy and Safety of Tirofiban in High‐Risk Patients With Non‐ST‐Segment Elevation Acute Coronary Syndromes

To evaluate the safety and efficacy of tirofiban in high risk patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) after percutaneous coronary intervention (PCI). A total of 240 patients were randomized to either a tirofiban group or a control group. Compared with the control group, the platelet aggregation rate in the tirofiban group was lower (P < 0.01); the plasma levels of CK-MB and troponin I, cardiac form (cTnI) were lower (P < 0.05); ECG improved significantly (P < 0.05); the incidence of major adverse cardiac events (MACE) was lower (P < 0.05); and there was no difference in bleeding complications between the 2 groups (P = 0.1). The administration of tirofiban in high risk patients with NSTE-ACS after PCI is safe and effective.

Defining the Role of Platelet Glycoprotein Receptor Inhibitors in STEMI

Tirofiban is a small molecule, nonpeptide tyrosine derivative. Although similar to abciximab in that it has a high specificity and affinity for the glycoprotein (GP) IIb/IIIa receptor, tirofiban dissociates from the GP IIb/IIIa receptor more rapidly than abciximab. Additionally, the action of tirofiban is reversed within hours after completion of the infusion, whereas abciximab binds irreversibly resulting in a considerably longer effect. The efficacy of tirofiban in ST-segment elevation myocardial infarction (STEMI) has been demonstrated when administered in patients being managed with primary percutaneous coronary intervention (PCI). These trials primarily studied tirofiban utilizing the high-dose bolus regimen (25 microg/kg bolus followed by a maintenance infusion of 0.15 microg/kg/min for 18-24 hours). The On-TIME (Ongoing Tirofiban in Myocardial Infarction Evaluation) 2 trial assessed early administration of the high-dose bolus regimen of tirofiban either at the referral centre or in the ambulance, in patients being transferred to a primary PCI centre. Early use of tirofiban resulted in both a significant increase in the rate of complete resolution of ST-segment deviation pre- and post-PCI, and improvement in clinical outcomes at 30 days. Moreover, the multi-factorial MULTISTRATEGY (Multicentre Evaluation of Single High-Dose Bolus Tirofiban vs Abciximab With Sirolimus-Eluting Stent or Bare Metal Stent in Acute Myocardial Infarction) trial, which compared the high-dose bolus regimen of tirofiban with standard dose administration of abciximab administered immediately prior to PCI, revealed similar effects on myocardial perfusion, ST-segment elevation recovery and clinical outcomes between the two agents, and confirmed the safety of tirofiban when used in combination with drug-eluting stents in patients with STEMI undergoing primary PCI. These studies showed tirofiban to be a well tolerated and effective GP IIb/IIIa inhibitor. On the basis of the demonstrated benefits of the high-dose bolus regimen, tirofiban may be considered useful in the management of patients with STEMI.

Evaluation on the safety and efficacy of tirofiban in the treatment of acute coronary syndrome

To evaluate the safety and efficacy of tirofiban, a specific inhibitor of the platelet glycoprotein llb/llla receptor, in the treatment of unstable angina and myocardial infarction without persistent ST elevation (acute coronary syndrome, ACS), a total of 200 patients were randomly assigned to a heparin group and a tirofiban+heparin group on double-blind basis and the treatment effects of the two protocols on ACS were compared when the patients of both groups were taking aspirin at the same time. The composite primary end-point events consisted of death, myocardial infarction, or refractory ischemia. Our results showed that the frequency of the composite primary end point events in 30 days was lower in tirofiban+heparin group as compared with that of heparin group (13.9% vs 29.3 %, P=0.010). The rates of the other composite end point events in the tirofiban+heparin group were also lower than those in the heparin group in 4.5 days and in 30 days. Bleeding complication occurred in 7.0% of the patients receiving heparin alone and in 12.7% of the patients receiving tirofiban and heparin in combination (P=0.1717). The study showed that the incidence of ischemic events in patients with ACS receiving tirofiban+heparin was lower when compared with that of patients who received only heparin and aspirin, suggesting that tirofiban might be of special value in the treatment of ACS.

The Long-Term Clinical Outcomes of Low Molecular Weight Heparin Combined with Platelet Glycoprotein IIb/IIIa Inhibitor in Patients with Acute Coronary Syndrome

Background and Objectives:Platelet activation and aggregation, with resultant arterial thrombus formation, play pivotal roles in the pathophysiology of acute coronary syndrome (ACS). The efficacy of tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, combined with heparin, or low molecular heparin (LMWH), in the management of ACS were evaluated. Subjects and Methods:One hundred seventeen patients (60.8± 10.9 years, 76 male), with unstable angina or non-ST elevation myocardial infarction, who had ST-T changes and elevated troponin, were divided into 4 groups:Group I (n=30:heparin alone), Group II (n=28:LMWH, dalteparin alone), Group III (n=29:tirofiban combined with heparin) and Group IV (n=30:tirofiban with LMWH). The major adverse cardiac events (MACE) among the 4 groups, during 6-month clinical follow-ups, were compared. Results:Percutaneous coronary intervention, or a coronary artery bypass graft, was performed in 23, 19, 19 and 22 patients from Groups I, II, III and IV, respectively (p=0.87). A minor bleeding complication developed in 2 (6.7%), 1 (3.6%), 1 (3.4%) and 2 patients (6.7%) in groups I, II, III and IV, respectively (p=0.79). During the six-month follow-up MACE occurred in 7 (30.4%), 6 (31.6%), 3 (15.8%) and 4 patients (18.2%) in groups I, II, III and IV, respectively (p=0.02:Group I and II vs. Group III and IV). Conclusion: Tirofiban combined with LMWH is safe and may improve the long-term prognosis of patients with ACS. (Korean Circulation J 2003;33 (7):559-567)

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.

Tirofiban: an investigational plateletglycoprotein IIb/IIIa receptor antagonist

The deposition of a platelet rich thrombus on an atherosclerotic plaque is a critical step in the development of unstable coronary syndromes. Currently available therapeutic agents such as aspirin and ticlopidine are relatively weak inhibitors of platelet aggregation. Recently, antagonists to platelet glycoprotein IIb/IIIa (GPIIb/IIIa), a platelet surface integrin whose activation and subsequent binding to fibrinogen is the final common step in the formation of platelet aggregates, have been utilised to treat unstable angina and myocardial infarction. Tirofiban is a novel, specific, low molecular weight GPIIb/IIIa receptor antagonist, which competitively inhibits the platelet fibrinogen receptor. Tirofiban is administered as an intravenous infusion with a mean half-life of 1.6 h. In healthy volunteers, the plasma concentration and half-life of tirofiban are unaffected by pre-treatment with aspirin, although aspirin increases the bleeding time prolongation caused by tirofiban. Tirofiban is excreted by both renal (37%) and non renal mechanisms. Three clinical trials, PRISM, PRISM PLUS, and RESTORE, have evaluated the safety and efficacy of tirofiban in unstable angina and in high-risk percutaneous transluminal coronary angioplasty (PTCA). When compared to heparin in the management of unstable angina, tirofiban decreased the odds of recurrent ischaemia, myocardial infarction, or death by 36% at 48 h, and death by 39% at 30 days. Similarly, the addition of tirofiban to heparin reduced the odds of recurrent ischaemic events for death at 7 days by 34%. RESTORE, a clinical trial evaluating the efficacy and safety of tirofiban in patients undergoing PTCA within 72 h of presentation with unstable angina or myocardial infarction, demonstrated a 38% reduction in a composite end-point at 48 h; the need for urgent PTCA and coronary artery bypass graft (CABG) at 30 days was reduced by 36%. Adverse side-effects, including major bleeding, were not significantly higher with tirofiban treatment. Tirofiban and other GPIIb/IIIa inhibitors represent a major advance in the treatment of unstable coronary syndromes and high-risk PTCA.