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

Azar, Rabih R.; Badaoui, Georges; Sarkis, Antoine; Kassab, Roland; Salamé, E; Aboujaoudé, Simon; Hamdan, Righab; Barakett, V.; Germanos, Mirna

doi:10.1002/clc.20424

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…Similarly, in type 2 diabetes mellitus, platelets are hypersensitive to agonists and respond to subthreshold stimuli before development of detectable vascular wall damage . Furthermore, GpIIbIIIa receptor inhibition with tirofiban in diabetic patients undergoing percutaneous cardiac interventions resulted in decreased inflammatory response . Experimental and clinical results show that activated platelets interact via surface molecules (ie, selectins) with circulating leukocytes and endothelium, causing inflammation and vascular diseases and contributing to disruption of endothelial barrier integrity .…”

Section: Discussionmentioning

confidence: 99%

“…53 Furthermore, GpIIbIIIa receptor inhibition with tirofiban in diabetic patients undergoing percutaneous cardiac interventions resulted in decreased inflammatory response. 55 Experimental and clinical results show that activated platelets interact via surface molecules (ie, selectins) with circulating leukocytes and endothelium, causing inflammation and vascular diseases and contributing to disruption of endothelial barrier integrity. 56 In our model, BBB permeability was compromised in all studied brain areas with the most significant permeability increase in the brain cortex.…”

Section: Discussionmentioning

confidence: 99%

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Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Adamski

Sternak

Mohaissen

et al. 2018

JAHA

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BackgroundAlthough advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved.Methods and ResultsTgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte‐specific overexpression of G‐αq*44 protein were studied before the end‐stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6‐ to 10‐month‐old but not in 3‐month‐old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood‐brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E‐selectin immunoreactivity, which was accompanied by increased amyloid‐β1‐42 accumulation in piriform cortex and increased cortical oxidative stress (8‐OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO‐dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3‐ to 10‐month‐old Tgαq*44 mice, but it was not associated with increased platelet‐dependent thrombogenicity.ConclusionsWe report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Adamski

Sternak

Mohaissen

et al. 2018

JAHA

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“…In study by Azar and colleagues in highrisk patients undergoing PCI, tirofiban significantly suppressed the rise of high sensitivity CRP [136]. Similarly, in a study by Walters and coworkers the combination of highdose tirofiban and enoxaparin resulted in an attenuated inflammatory response compared to the combination of high-dose tirofiban and unfractionated heparin [137].…”

Section: Off-target Effectsmentioning

confidence: 90%

Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future

Luca

Savonitto

Hof

et al. 2015

Drugs

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Coronary artery disease and acute myocardial infarction still represent the leading cause of mortality in developed countries. Therefore, great efforts have been made in the last decades to improve reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite optimal epicardial recanalisation, a large proportion of patients still experience impaired reperfusion and in-stent thrombosis. The adjunctive use of glycoprotein (GP) IIb-IIIa inhibitors may certainly contribute in the reduction of such complications, especially when administered in the early phase of infarction. In fact, in this phase a larger platelet composition of the thrombus and the presence of a larger amount of viable myocardium, as compared to a delayed phase, may increase the benefits from this therapy and counterbalance the potential higher risk of bleeding. A large body of evidence has been accumulated on the benefits from GP IIb-IIIa inhibitors in terms of prevention of stent thrombosis, and benefits in mortality, especially among high-risk patients and as upstream strategy. Therefore, based on current available data, GP IIb-IIIa inhibitors can be recommended as early as possible (upstream strategy) among high-risk patients, such as those with advanced Killip class or anterior myocardial infarction (MI), and those presenting within the first three hours. Even though it is not universally accepted, in our opinion this strategy should be implemented in a pre-hospital setting (in ambulance) or at first hospital admission (Emergency Room or Coronary Care Unit, irrespective of whether they are in the spoke or hub hospitals). Peri-procedural intracoronary administration of GP IIb-IIIa inhibitors has not provided additional benefits as compared to intravenous administration and therefore cannot be recommended. Even though the vast majority of trials have been conducted with abciximab, several meta-analyses comparing small molecules (mainly high-dose tirofiban rather than eptifibatide) versus abciximab showed similar angiographic and clinical results between the molecules. Several recent investigations and meta-analyses have documented the higher risk of stent thrombosis associated with bivalirudin as compared to unfractionated heparin (UFH). Being that these results are independent from the use of GP IIb-IIIa inhibitors, UFH should still remain the anticoagulation therapy of choice in ST-segment elevation myocardial infarction (STEMI) patients. Minimisation of bleeding complications by extensive use of the radial approach, in the setting of STEMI, may further contribute to the adoption of a more aggressive antithrombotic and antiplatelet therapy incorporating the use of GP IIb-IIIa inhibitors. The establishment of dedicated networks for STEMI, and the large STEMI campaign, will certainly contribute to increase the proportion of patients presenting at first medical contact within the early phase (3 h) of infarction and therefore highly suitable for a more aggressive pharmacoinvasive approach with upstream administration of GP IIb-II...

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“…The result of this study shows that by comparing the electrocardiographic lead ST segment resolution of the early-treated patients and the late-treated patients after 90 min recanalization, the ST segment resolution of the former is remarkably higher than that of the later. The possible reasons may be that there is a small difference between the time of using tirofiban to the early-treated patients before operation and the late-treated patients and the relevant related artery gets infarcted in time, thus causing no statistical difference in evolution of myocardial enzyme and LEVF determination [12,13]. …”

Section: Discussionmentioning

confidence: 99%

Analysis of the Best Timing for Applying Tirofiban in PCI Operation for the Patients with ST Segment Elevation Myocardial Infarction

Zhang

et al. 2015

Open Medicine

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This study is a comparative analysis of the best timing for applying tirofiban in the PCI emergency treatment for STEMI patients. We selected 109 patients with ST-segment elevation myocardial infarction from October 2013 to October 2014 and divided them into two groups, the early treatment group (53 cases) received tirofiban during the operation and the later treatment group (56 cases) received tirofiban after operation. The analysis was then conducted. Results: The proportion of IRA forward flow in TIMI2-3 for the 1st group during the radiography was higher than 2nd group, 50 cases with TIMI3 blood flow and 52 cases with TIMI3 blood flow in later treatment group. Comparing the TIMI3 flow of both groups, the difference was not statistically significant; for the CK-MB 4h and 8h after operation as well as the LVEF after operation, the differences are were not statistically significant. The occurrence rate of hemorrhage complication was low for both groups. The early use of tirofiban can make the thrombus fully dissolve and coronary blood flow remains in a good state, which is not only beneficial for myocardial perfusion but also helpful for deciding the length and side branch situation of coronary artery pathological changes.

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

Cited by 10 publications

References 21 publications

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice

Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future

Analysis of the Best Timing for Applying Tirofiban in PCI Operation for the Patients with ST Segment Elevation Myocardial Infarction

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