Suboptimal early inhibition of platelets by treatment with tirofiban and implications for coronary interventions

Kabbani, Samer; Aggarwal, Atul; Terrien, Edward F.; DiBattiste, Peter M.; Sobel, Burton E.; Schneider, David J.

doi:10.1016/s0002-9149(01)02319-0

Cited by 87 publications

(58 citation statements)

References 18 publications

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“…4 The main limitation of that bolus dose is its failure to consistently suppress platelet aggregation by >80%-90% at the time of PCI. 5 Less than optimal inhibition of platelet aggregation may paradoxically result in higher release of sCD40L and thus, more inflammation. 13 Contrary to tirofiban, a study with abciximab demonstrated suppression of the inflammatory response following PCI.…”

Section: Comparison With Prior Studiesmentioning

confidence: 99%

“…3,4 We previously tested the effects of tirofiban on inflammatory markers following PCI, and demonstrated that it does not attenuate the rise of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP), when it is given immediately prior to PCI in patients with stable coronary artery disease (CAD). 4 In that study, we used a 10 µg/kg loading dose of tirofiban followed by 0.15 µg/kg/min continuous infusion for 24 h. That regimen however, does not consistently achieve significant platelet inhibition at the time of PCI, 5 which may explain its failure to suppress inflammation. 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.…”

mentioning

confidence: 99%

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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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Section: Comparison With Prior Studiesmentioning

confidence: 99%

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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“…[6][7][8][9] The TARGET dosing regimen of tirofiban inhibited 20 µM ADPinduced aggregation by only 60 to 66%. 6,7 This in contrast to abciximab, as it was dosed in the TARGET trial, which inhibited 90 to 95% of aggregation.…”

mentioning

confidence: 99%

“…6,7 This in contrast to abciximab, as it was dosed in the TARGET trial, which inhibited 90 to 95% of aggregation. 6,7,9 This difference in the extent of inhibition of platelet aggregation has been proposed as the reason why more procedure-related ischaemic events occurred among subjects receiving tirofiban in the TARGET. Higher dosing may improve outcome and this hypothesis needs to be tested in a clinical trial.…”

mentioning

confidence: 99%

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

Werkum¹,

Gerritsen²,

Kelder³

et al. 2007

NHJL

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Background. 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. Methods. 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. Results. 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).

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“…6 The authors refer to studies using TARGET trial dosing, in which low-dose tirofiban achieved only 60 to 66% platelet inhibition and resulted in more procedure-related ischaemic events than abciximab, which produced 90 to 95% platelet inhibition (using optical light aggregometry). 7,8 Therefore, Van Werkum et al used the high-dose tirofiban instead, for comparison with abciximab and placebo. Nevertheless, even in the high-dose tirofiban, there was still considerable platelet aggregation in vitro (20% of platelets).…”

mentioning

confidence: 99%

Does glycoprotein IIB/IIIA resistance exist?

Smit¹,

Hof²

2007

NHJL

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Suboptimal early inhibition of platelets by treatment with tirofiban and implications for coronary interventions

Cited by 87 publications

References 18 publications

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

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

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

Does glycoprotein IIB/IIIA resistance exist?

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