Enhanced early inhibition of platelet aggregation with an increased bolus of tirofiban

Schneider, David J.; Herrmann, Howard C.; Lakkis, Nasser; Aguirre, Frank V.; Wan, Ying; Aggarwal, Atul; Kabbani, Samer; DiBattiste, Peter M.

doi:10.1016/s0002-9149(02)02892-8

Cited by 69 publications

(53 citation statements)

References 10 publications

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“…As predicted by Schneider et al [32] from in vitro studies of highdose tirofiban dosing, the current study has demonstrated a consistently high level of platelet inhibition. These are the kinds of levels of platelet inhibition that are considered necessary to achieve optimal clinical outcome for patients with high-risk acute coronary syndrome undergoing PCI [33].…”

Section: Discussion Effect Of Hd-tirofibansupporting

confidence: 85%

High‐dose tirofiban with enoxaparin and inflammatory markers in high‐risk percutaneous intervention

Walters¹,

Ray²,

Wood³

et al. 2010

Eur J Clin Investigation

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Aim The study assessed the benefit of high bolus dose tirofiban (HD-tirofiban) with enoxaparin compared with HD-tirofiban with unfractionated heparin (UFH). The study examined markers of platelet activation, thrombin generation and inflammation. Materials and methodsThe study is a prospective single centre open-label trial of patients with high-risk acute coronary syndrome treated with percutaneous intervention (PCI) who were randomized to anticoagulation with UFH or enoxaparin with HD-tirofiban (25 lg kg )1 bolus). This study measured a panel of platelet activation markers, inflammatory biomarkers and thrombus generation between the two groups.Result Sixty patients undergoing high-risk PCI were enroled in the study. Platelet inhibition as assessed by whole blood aggregometry following HD-tirofiban infusion was similar in both the UFH and enoxaparin groups. CD40 ligand expression on platelets was significantly reduced following PCI with HD-tirofiban and either UFH or enoxaparin. Following PCI, there were significant reductions measured in other markers of platelet activation including PAC-1, P selectin, factor V ⁄ Va, platelet-monocyte aggregates and monocyte expression of Mac-1 as determined by analysis of venous blood samples using flow cytometry. Prothrombin fragment 1+2, D-dimer, von Willebrand factor and high sensitive C-reactive protein levels were significantly less post PCI in the enoxaparin group compared with those patients receiving UFH. ConclusionThe combination of HD tirofiban with enoxaparin resulted in an attenuated inflammatory response when compared with that of the combination of HD tirofiban with UFH.

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Section: Discussion Effect Of Hd-tirofibansupporting

confidence: 85%

High‐dose tirofiban with enoxaparin and inflammatory markers in high‐risk percutaneous intervention

Walters¹,

Ray²,

Wood³

et al. 2010

Eur J Clin Investigation

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“…29 Schneider et al showed that the lesser degree of initial inhibition of platelet aggregation using tirofiban was dose-dependent compared to abciximab. " 30 A recent meta-analysis showed that there was a reduction in major adverse coronary events through addition of tirofiban to aspirin and clopidogrel, among patients with ST-elevation myocardial infarction prior to percutaneous coronary intervention. 31 Blood rheological changes, such as blood viscosity, increased serum levels of fibrinogen, inflammatory cytokines and others, could explain the variability of platelet response.…”

Section: After Tirofiban Administrationmentioning

confidence: 99%

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

et al. 2016

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CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations. DESIGN AND SETTING: Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo. METHOD: Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T), Ib (Thr/Met), IIb (Ile/Ser) and IIIa (PIA) were the mutations selected. RESULTS: Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality. CONCLUSIONS: Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction. RESUMO CONTEXTO E OBJETIVOS:Inibidores da glicoproteína (abciximab, eptifibatide, tirofiban) são utilizados em pacientes com angina instável e infarto do miocárdio sem elevação do segmento ST (IAMSSST) antes da intervenção coronária percutânea. Dentre eles, o tirofiban é o menos eficaz. Nossa hipótese é que a resposta ao tirofiban possa estar associada a mutações no gene da glicoproteína. DESENHO E LOCAL: Estudo prospectivo na Unidade de Emergência do Instituto do Coração (InCor), Universidade de São Paulo (USP).MÉTODOS: Foram analisadas a evolução intra-hospitalar e agregabilidade plaquetária em resposta ao tirofiban de 4 mutações da glicoproteína em 50 pacientes com indicação para intervenção coronária percutânea, 17 (34%) com angina instável e 33 (66%) com IAMSSST. A agregação plaquetária foi analisada pelo método de Born. Amostras de sangue foram obtidas antes e uma hora após infusão do tirofiban. As glicoproteínas Ia (807C/T), Ib (Thr/Met), IIb (Ile/Ser) e IIIa (PIA) foram as mutações selecionadas. RESULTADOS: Hipertensão, dislipidemia, diabetes, tabagismo, doença coronariana e acidente vascular cerebral prévios foram semelhantes entre os grupos. Observou-se menor agregabilidade plaquetária dos genótipos mutantes da...

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“…4 A new regimen of tirofiban administration which consists of a higher bolus (25 µg/kg) followed by the same 0.15 µg/kg/min continuous infusion was recently described. 6 It allows a rapid inhibition of platelet aggregation by more than 90%, and was proven in randomized clinical trials to improve clinical outcome following PCI. 7,8 Its effect on inflammatory mediators remains however, unknown.…”

mentioning

confidence: 99%

Effect of High Bolus Dose Tirofiban on the Inflammatory Response Following Percutaneous Coronary Intervention

Azar¹,

Badaoui²,

Sarkis³

et al. 2010

Clinical Cardiology

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Background: Tirofiban at the bolus dose of 10 µg/kg does not suppress the inflammatory response following percutaneous coronary intervention (PCI). This may be due to less than optimal inhibition of platelet aggregation. High bolus dose tirofiban (25 µg/kg) allows better inhibition of platelet aggregation but its anti-inflammatory effect remains unknown. Hypothesis: High bolus dose tirofiban exhibits anti-inflammatory activity. Methods: A total of 100 patients referred for PCI were randomized to receive high bolus dose tirofiban followed by a 24-h infusion or a bolus and an infusion of saline. Patients with elevated troponin or with thrombus in the culprit lesion were excluded. Inflammatory markers were measured at baseline and at 24 h. Results: Levels of soluble CD40 ligand (sCD40L) were not affected by PCI while those of interleukin-6 (IL-6) and of high sensitivity C-reactive protein (hs-CRP) significantly increased. Despite inhibiting platelet's aggregation by >90%, tirofiban did not suppress the rise of IL-6 and hs-CRP. Median (interquartile range) elevation of IL-6 was 0.6 pg/mL (−1.5-3.6) versus 0.4 pg/mL (−0.7-1.8) and that of hs-CRP was 2.1 mg/L (0.7-5.2) versus 2.4 mg/L (1-4.7) in the tirofiban and the control groups, respectively (p = ns). However, in patients with diabetes mellitus, tirofiban significantly suppressed the rise of hs-CRP by 65% (p = 0.01), but did not significantly affect the rise of IL-6. Conclusion: In low-risk patients undergoing PCI, tirofiban did not attenuate the rise of inflammatory markers. However, the significant effect in diabetics suggests that tirofiban may have anti-inflammatory activity in higher risk patients.

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Enhanced early inhibition of platelet aggregation with an increased bolus of tirofiban

Cited by 69 publications

References 10 publications

High‐dose tirofiban with enoxaparin and inflammatory markers in high‐risk percutaneous intervention

High‐dose tirofiban with enoxaparin and inflammatory markers in high‐risk percutaneous intervention

Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome

Effect of High Bolus Dose Tirofiban on the Inflammatory Response Following Percutaneous Coronary Intervention

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