Brief report

Comparison of degree of platelet inhibition by abciximab versus tirofiban in patients with unstable angina pectoris and non–Q-wave myocardial infarction undergoing percutaneous coronary intervention☆

Pre-procedural platelet reactivity has been correlated with adverse ischemic events following percutaneous coronary intervention. Patients with high pre-percutaneous coronary intervention platelet reactivity demonstrate a differential response to standard doses of antiplatelet therapies and have higher residual post-treatment platelet reactivity. Peri-procedural platelet inhibition has been inversely correlated with the occurrence of adverse clinical outcomes, particularly myocardial infarction. Preliminary evidence supports the concept of a threshold for post-treatment platelet reactivity, and patients with less than 40% to 50% residual aggregation in response to 20-μmol/l adenosine diphosphate appear to have the best long-term clinical outcomes. Wide interindividual variability in response to either aspirin or clopidogrel has been demonstrated, and hyporesponsiveness to either agent has been associated with adverse clinical outcomes. Although the prevalence of either aspirin or clopidogrel resistance may be reduced by increasing the dose of medication, it cannot be eliminated, and interindividual variability in response persists. The advent of direct-acting antithrombin agents for peri-procedural anticoagulation coupled with novel antiplatelet therapies on the immediate horizon promise to enhance the safety and efficacy of peri-procedural adjunctive pharmacotherapy.

The TARGET study has been criticised for sub-optimal platelet inhibition with tirofiban. We aimed to compare a high-dose bolus regimen of tirofiban (hd-tirofiban) to standard dose of abciximab for patients undergoing percutaneous coronary intervention (PCI).

We assessed consecutive patients who received either hd-tirofiban (25 mcg/kg bolus followed by 0.15 mcg/kg/min infusion for 18 h) or standard dose abciximab. In-hospital and 6-month outcomes were obtained in all cases.

Over an 18-month period, 109 patients who received hd-tirofiban were compared with 110 patients who received abciximab. Both hd-tirofiban and abciximab groups had acute coronary syndromes in 86% and 80% and diabetes in 10% and 13% respectively. Most patients had coronary stent implantation (96% vs. 98%).

Thrombocytopenia (platelet count < 100,000) developed in 0.9% of patients receiving hd-tirofiban and 2% of patients receiving abciximab (p = 0.566). Bleeding requiring transfusion occurred in 7.3% and 3% of patients respectively (p = 0.118). Peri-procedural troponin rise was 0.9% in patients receiving hd-tirofiban and 5.5% in patients receiving abciximab (p = 0.07). MACE (Myocardial infarction, Stroke, Revascularisation and Death) at 6 months was 23% in the hd-tirofiban group and 20% in the abciximab group (p = 0.711). The pharmaceutical costs were AUD 322 for hd-tirofiban (one ampoule) and AUD 1350 for abciximab (3 ampoules).

There was a small increase in bleeding requiring transfusion and a lower rate of peri-procedural troponin rise in the hd-tirofiban group however, the overall 6-month MACE rates were similar in both groups. There was a considerable cost-saving with the use of hd-tirofiban. A prospective randomised trial of hd-tirofiban vs. abciximab is warranted.

The Ultegra Rapid Platelet Function Assay was used to measure the inhibition of platelet aggregation at baseline and 10 minutes and 8 hours after starting therapy in 114 patients undergoing high-risk percutaneous coronary intervention with the planned use of a glycoprotein IIb/IIIa inhibitor. The abciximab-treated patients received a 0.25 mg/kg bolus, followed by a 0.125 μg/kg/min infusion for 12 hours; the eptifibatide-treated patients received 2 boluses of 180 μg/kg administered 10 minutes apart, followed by a 2 μg/kg/min infusion for 24 hours; the tirofiban-treated patients received a 25 μg/kg bolus, followed by a 0.15 μg/kg/min infusion for 18 hours. Ten minutes after starting therapy, the mean level of platelet inhibition was 86 ± 9% for abciximab, 92 ± 6% for eptifibatide, and 95 ± 5% for tirofiban (p <0.001); ≥95% platelet inhibition was achieved in 29% of the patients treated with abciximab, 44% of those receiving eptifibatide, and 68% of the those receiving tirofiban (p = 0.02). In conclusion, at the evaluated doses, tirofiban seemed to be the most effective drug in achieving “optimal” platelet inhibition very early after percutaneous coronary intervention.

The best treatment option for high-risk patients with unstable coronary syndrome is an early invasive strategy accompanied by intensive anti-platelet therapy. We tested the effect on clinical outcome of early coronary angioplasty using a high-dose bolus of tirofiban in patients with non-ST segment elevation acute coronary syndrome.

One hundred and forty consecutive patients with unstable coronary syndrome who underwent an immediate percutaneous coronary intervention with the administration of a high (25 μg/kg) dose bolus of tirofiban followed by an 18-h infusion of 0.15 μg kg⁻¹ min⁻¹ were compared with a matched control group of 162 patients treated with abciximab. The primary endpoint of the study was the 30-day incidence of major adverse cardiac events; the secondary endpoints were the incidence of major and minor bleeding.

The time from admission to PCI was slightly shorter in the tirofiban group (3.9 ± 4.8 vs. 4.5 ± 4.4 h; P = 0.26). The 30-day rate of major adverse cardiac events was similar in the two groups (6% with tirofiban and 8.6% with abciximab: OR = 1.37, 95% CI = 0.58–3.29, P = 0.52). No major bleeding episodes were observed; the incidence of minor bleeding was 3.6% in the tirofiban group and 2.5% in the abciximab group (OR = 0.68, 95% CI = 0.18–2.59, P = 0.74).

In this preliminary study, the beneficial effect of the administration of a high-dose tirofiban bolus on 30-day clinical outcomes was similar to that of abciximab in high-risk patients with unstable angina undergoing immediate percutaneous coronary intervention. The results of this therapeutic strategy should be tested in a larger randomised study.

We endeavored to determine under what conditions a strategy of upstream use of small molecule platelet glycoprotein (GP) IIb/IIIa inhibitors for all acute coronary syndromes (ACS) patients is cost effective compared to that of selective use of abciximab in only those patients requiring percutaneous coronary intervention (PCI).

Small molecule GP IIb/IIIa inhibitors have shown benefit in ACS, but abciximab, the more expensive GP IIb/IIIa inhibitor, may be more effective during PCI. However, abciximab does not have proven efficacy in medical management. No prior study has attempted to balance these competing benefits.

A decision analysis was performed to examine two strategies: 1) treat all ACS patients upstream with a small molecule GP IIb/IIIa inhibitor and continue through medical management and PCI, if performed; or 2) wait, and selectively use abciximab only in patients who ultimately undergo PCI. Applicable randomized controlled trial data were used for the principal analysis.

The strategy of upstream use of a small molecule GP IIb/IIIa inhibitor was superior to selective use, and economically acceptable, with a cost-effectiveness ratio of $18,000 per year of life gained. The superiority of the upstream use strategy persisted over the majority of sensitivity analyses. When stratified by risk according to Thrombolysis in Myocardial Infarction risk score, a strategy of upstream use was only cost effective in those patients with moderate or high risk.

Upstream use of small molecule GP IIb/IIIa inhibition in ACS patients with moderate or high risk for cardiovascular events is a cost-effective approach that should be considered in this subset of patients.

Despite extensive data supporting the use of platelet glycoprotein (GP) IIb/IIIa (GPIIb/IIIa) inhibitors in the therapy of patients with acute coronary syndromes (ACS), there is considerable debate as to the optimal choice of antiplatelet regimen. The objective of this study was to conduct a detailed time-resolved analysis of the effects of the GPIIb/IIIa inhibitor tirofiban with concomitant clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI) to improve the dosing regimen of these two commonly used antiplatelet drugs.

The study was performed in 14 patients with non-ST-segment elevation (NSTE) ACS who underwent PCI while being treated with the current typically utilized regimen of tirofiban (10 μg/kg bolus, 0.15 μg/kg/min infusion) and clopidogrel (300 mg). Platelet function was assessed before, during, and after tirofiban infusion using a panel of agonists for ADP receptors, PAR1 and PAR4 thrombin receptors, and collagen receptors.

Measurements of circulating tirofiban levels demonstrated a trough, which paralleled a reduction in platelet inhibition for all platelet agonists during the time when PCI was being performed. Interestingly, younger ACS patients (<55 years) exhibited less inhibition of platelet function both during the PCI procedure and after termination of the tirofiban infusion. These apparent age differences were primarily attributed to a decreased responsiveness of the younger patients to clopidogrel.

This study shows that the currently utilized tirofiban dosage is suboptimal and suggests that patients may benefit from a higher dose regimen.