Simultaneous integrin αβ and glycoprotein IIb/IIIa inhibition causes reduction in infarct size in a model of acute coronary thrombosis and primary angioplasty

Sakuma, Tadamichi; Sarı, İbrahim; Goodman, Craig N.; Lindner, Jonathan R.; Klibanov, Alexander L.; Kaul, Sanjiv

doi:10.1016/j.cardiores.2005.01.016

Cited by 48 publications

(34 citation statements)

References 31 publications

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“…In a model of acute coronary thrombosis and primary PCI, Sakuma and coworkers found that simultaneous inhibition of GP IIb-IIIa and integrin avb3 causes a marked reduction in infarct size that is associated with reduced myocardial micro-thrombi and inflammation, as well as improved myocardial blood flow and regional function [127].…”

Section: Off-target Effectsmentioning

confidence: 98%

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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Section: Off-target Effectsmentioning

confidence: 98%

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

Luca

Savonitto

Hof

et al. 2015

Drugs

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“…To detect thrombi formed at the culprit lesion, radiolabeled fibrinogen, and antibodies against fibrin and plasminogen activator have been developed. Among them, several animal studies used 99m Tc-labeled platelet glycoprotein IIb/IIIa receptor agonist to detect thrombi [26,27].…”

Section: Nuclear Imaging Of Other Biological Processes Associated Witmentioning

confidence: 99%

Molecular Imaging of Macrophages in Atherosclerosis

Aïkawa

New

Miyazaki

et al. 2011

Curr Cardiovasc Imaging Rep

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Macrophages contribute to the initiation, progression, and acute complications of atherosclerosis. Imaging of macrophages during disease progression provides new insights into the mechanisms of atherosclerosis. Advanced imaging techniques may serve as sensitive diagnostic tools for early detection of the disease to identify individuals with subclinical plaques and to prevent devastating complications. Furthermore, molecular imaging may monitor the effects of therapeutic interventions. Development of fully integrated molecular imaging requires dynamic multidisciplinary collaboration.

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“…Sakuma et al [38] compared the effect of the combined blockade of the GP IIb/IIIa receptor and integrin avb3 with the blockade of GP IIb/IIIa receptor alone, using a highly specific inhibitor -tirofiban, relating the results to a control group receiving saline. They found that out of these 3, simultaneous inhibition of GP IIb/IIIa and integrin avb3 cause a marked reduction in infarct size, in a model of acute coronary thrombosis and primary PCI, which is associated with reduced myocardial microthrombi and inflammation, as well as improved myocardial blood flow and regional function [38].…”

Section: Abciximabmentioning

confidence: 99%

“…They found that out of these 3, simultaneous inhibition of GP IIb/IIIa and integrin avb3 cause a marked reduction in infarct size, in a model of acute coronary thrombosis and primary PCI, which is associated with reduced myocardial microthrombi and inflammation, as well as improved myocardial blood flow and regional function [38]. Abciximab was not used in the study, but as far as we know, abciximab inhibits both -the GP IIb/IIIa receptor and integrin avb3, so we may assume that the effect would be similar.…”

Section: Abciximabmentioning

confidence: 99%