Integrin αIIbβ3: From Discovery to Efficacious Therapeutic Target.
Abstract
From the initial description of platelets in 1882, their propensity to aggregate and to contribute to thrombosis was apparent. Indeed, excessive platelet aggregation is associated with myocardial infarction and other thrombotic diseases whereas Glanzmann thrombasthenia, in which platelet aggregation is reduced, is a bleeding syndrome. Over the last half of the 20th century, many investigators have provided insights into the cellular and molecular basis for platelet aggregation. The major membrane protein on platelets, integrin αIIbβ3, mediates this response by rapidly transiting from its resting...
Source: Circulation Research - April 12, 2013 Category: Cardiology Authors: Bledzka K, Smyth SS, Plow EF Tags: Circ Res Source Type: research
Transport Limitations of Nitric Oxide Inhibition of Platelet Aggregation under Flow.
In this study, a NO releasing polymer, diazeniumdiolated dibutylhexanediamine, was integrated into a microfluidic flow assay to determine the relationship between NO wall flux and collagen mediated platelet adhesion, activation and aggregation. A NO flux equal to or greater than 2.5 × 10(-10) mol cm(-2) min(-1) was found to abrogate aggregation, but not initial platelet adhesion, on collagen at 200 and 500 s(-1) as effectively as the α IIb β 3 antagonist abciximab. The dynamic range of NO fluxes found to induce measurable inhibition of platelet aggregation spanned from 0.33 × 10(-10) to 2.5 × 10(-10) mol c...
Source: Annals of Biomedical Engineering - April 6, 2013 Category: Biomedical Engineering Authors: Sylman JL, Lantvit SM, Vedepo MC, Reynolds MM, Neeves KB Tags: Ann Biomed Eng Source Type: research
Randomized trial of standard versus ClearWay-infused abciximab and thrombectomy in myocardial infarction: rationale and design of the COCTAIL II study
Conclusion: This trial will provide important mechanistic insights on the most appropriate invasive treatment strategy for patients with STEMI and significant thrombus burden, by exploiting its factorial design and reliance on sensitive OCT endpoints. (Source: Journal of Cardiovascular Medicine)
Source: Journal of Cardiovascular Medicine - April 3, 2013 Category: Cardiology Tags: Original articles: Coronary artery disease Source Type: research
The bivalirudin paradox: high evidence, low use
A series of trials have shown that bivalirudin, a direct thrombin inhibitor that does not require the cofactor antithrombin III to be effective, is a reasonable alternative to unfractionated heparin (UFH) alone or associated with glycoprotein IIb/IIIa antagonists (GPI) in patients undergoing percutaneous coronary interventions (PCI). Particularly in patients with acute coronary syndromes (ACS), the effects of bivalirudin are striking. In the HORIZONS-AMI trial, patients with persistent ST-segment elevation (STEMI) had lower 30-day rates of net adverse clinical events and major bleeding, largely due to the significantly low...
Source: Journal of Cardiovascular Medicine - April 3, 2013 Category: Cardiology Tags: Reviews: Coronary artery disease Source Type: research
Gender differences in long‐term outcome after primary percutaneous intervention for st‐segment elevation myocardial infarction
ConclusionWomen have higher rates of both MACE and mortality after primary PCI for STEMI compared to men because of higher age with higher baseline risk profiles. © 2013 Wiley‐Liss, Inc. (Source: Catheterization and Cardiovascular Interventions)
Source: Catheterization and Cardiovascular Interventions - April 1, 2013 Category: Cardiovascular & Thoracic Surgery Authors: Inge Wijnbergen, Jan Tijssen, M. van 't Veer, Rolf Michels, Nico H.J. Pijls Tags: Original Study Source Type: research
Abciximab During Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Intracoronary, Intravenous, or Not at All? ⁎ ⁎
The intravenous (IV) route is the standard way to administer abciximab to patients during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), but pharmacokinetic principles predict that the intracoronary (IC) route would be better. Because of the short half-life of abciximab and its avid binding to multiple integrin types during the first pass through the systemic circulation, less drug may reach exposed IIb/IIIa epitopes on activated platelets within the culprit lesion after IV bolus than after direct IC administration (1). Supporting this concept, a small mechanistic study of ...
Source: Journal of the American College of Cardiology: Cardiovascular Interventions - March 25, 2013 Category: Cardiology Source Type: research
Intracoronary Compared With Intravenous Bolus Abciximab Application During Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction Cardiac Magnetic Resonance Substudy of the AIDA STEMI Trial
ConclusionsThis largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events. (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction [AIDA STEMI]; NCT00712101) (Source: Journal of the American College of Cardiology: Cardiovascular Interventions)
Source: Journal of the American College of Cardiology: Cardiovascular Interventions - March 25, 2013 Category: Cardiology Source Type: research
Long-Term Prognostic Benefit of Field Triage and Direct Transfer of Patients With ST-Segment Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention
Direct transfer (DT) to the catheterization laboratory has been demonstrated to reduce delays in primary percutaneous coronary intervention (PPCI). However, data with regard to its effect on long-term mortality are sparse. The aim of this study was to investigate the effect of DT on long-term mortality in patients with ST-segment elevation myocardial infarctions treated with PPCI. A cohort study was conducted of 1,859 patients (mean age 63.1 ± 13 years, 80.2% men) who underwent PPCI from May 2005 to December 2010. From the whole series, 425 patients (23%) were admitted by DT and 1,434 (77%) by emergency departments. DT p...
Source: The American Journal of Cardiology - March 18, 2013 Category: Cardiology Authors: Rodrigo Estévez-Loureiro, Ramón Calviño-Santos, Ángela López-Sainz, José Manuel Vázquez-Rodríguez, María Rita Soler-Martín, Oscar Prada-Delgado, Eduardo Barge-Caballero, Jorge Salgado-Fernández, Guillermo Aldama-López, Pablo Piñón-Esteban, X Tags: Coronary Artery Disease Source Type: research
Intracoronary Compared With Intravenous Bolus Abciximab Application During Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: Cardiac Magnetic Resonance Substudy of the AIDA STEMI Trial
Conclusions:
This largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events. (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction [AIDA STEMI]; NCT00712101) (Source: Journal of the American College of Cardiology)
Source: Journal of the American College of Cardiology - March 4, 2013 Category: Cardiology Authors: Ingo Eitel, Jochen Wöhrle, Henning Suenkel, Josephine Meissner, Sebastian Kerber, Bernward Lauer, Matthias Pauschinger, Ralf Birkemeyer, Christoph Axthelm, Rainer Zimmermann, Petra Neuhaus, Oana Brosteanu, Suzanne de Waha, Steffen Desch, Matthias Gutberl Tags: EXPEDITED PUBLICATIONS Source Type: research
Abciximab During Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: Intracoronary, Intravenous, or Not at All?⁎
The intravenous (IV) route is the standard way to administer abciximab to patients during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), but pharmacokinetic principles predict that the intracoronary (IC) route would be better. Because of the short half-life of abciximab and its avid binding to multiple integrin types during the first pass through the systemic circulation, less drug may reach exposed IIb/IIIa epitopes on activated platelets within the culprit lesion after IV bolus than after direct IC administration (). Supporting this concept, a small mechanistic study of 1...
Source: Journal of the American College of Cardiology - March 4, 2013 Category: Cardiology Authors: John A. Bittl Tags: Editorial Comment Source Type: research
Impact of multivessel disease on myocardial perfusion and survival among patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitors.
CONCLUSIONS: Among patients with ST-elevation myocardial infarction undergoing primary angioplasty with GP IIb/IIIa inhibitor treatment, the extent of coronary artery disease was independently associated with impaired myocardial perfusion and survival.
PMID: 23582677 [PubMed - in process] (Source: Archives of Cardiovascular Diseases)
Source: Archives of Cardiovascular Diseases - March 1, 2013 Category: Cardiology Authors: De Luca G, Gibson M, Cutlip D, Huber K, Dudek D, Bellandi F, Noc M, Maioli M, Zorman S, Zeymer U, Secco GG, Mesquita Gabriel H, Emre A, Arntz HR, Rakowski T, Gyongyosi M, Hof AW, EGYPT Cooperation Tags: Arch Cardiovasc Dis Source Type: research
Tirofiban-induced acute profound thrombocytopenia after primary angioplasty [CASE STUDIES]
We describe a case of acute profound thrombocytopenia due to on tirofiban treatment in a patient who underwent primary angioplasty. (Source: Asian Cardiovascular and Thoracic Annals)
Source: Asian Cardiovascular and Thoracic Annals - February 21, 2013 Category: Cardiology Authors: Dursunoglu, Taskoylu, Gur, Sari Tags: CASE STUDIES Source Type: research
Sex-related effectiveness of bivalirudin versus abciximab and heparin in non–ST-segment elevation myocardial infarction
Conclusion: Despite a higher peri-PCI bleeding risk in women, bivalirudin is as effective as and safer than abciximab plus heparin in women and men with NSTEMI undergoing PCI. (Source: American Heart Journal)
Source: American Heart Journal - February 20, 2013 Category: Cardiology Authors: Julinda Mehilli, Franz-Josef Neumann, Gjin Ndrepepa, Lamin King, Stefanie Schulz, Fatima Maimer Rodrigues da Cunha, David Jochheim, Robert A. Byrne, Jörg Hausleiter, Ilka Ott, Steffen Massberg, Adnan Kastrati, Jürgen Pache Tags: Acute Ischemic Heart Disease Source Type: research
Clinical outcomes and cost implications of routine early PCI after fibrinolysis: One-year follow-up of the Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) study
Conclusions: At 1 year, there is no difference in the clinical composite outcome of death or reinfarction between r-PCI and s-PCI strategies. Greater cost with r-PCI, although statistically insignificant, is economically important. (Source: American Heart Journal)
Source: American Heart Journal - February 20, 2013 Category: Cardiology Authors: Akshay Bagai, Warren J. Cantor, Mary Tan, Wesley Tong, Andre Lamy, David Fitchett, Eric A. Cohen, Shamir R. Mehta, Bjug Borgundvaag, John Ducas, Michael Heffernan, Vladimír Džavík, Laurie Morrison, Brian Schwartz, Charles Lazzam, Anatoly Langer, Shaun Tags: Outcomes, Health Policy, and Managed Care Source Type: research
Local increase in microparticles from the aspirate of culprit coronary arteries in patients with ST-segment elevation myocardial infarction
Conclusion: Locally increased levels of MPs in culprit coronary arteries and their significant reduction after successful PCI suggest a potential role in coronary atherothrombosis in the early period of STEMI.Highlights: ► Microparticles were higher in infarct-related arteries than in peripheral arteries. ► Coronary intervention significantly lowered intracoronary microparticles. ► Abciximab seemed to mainly affect the level of microparticles in peripheral artery. ► Microparticles may play a role in coronary atherothrombosis. (Source: Atherosclerosis)
Source: Atherosclerosis - February 19, 2013 Category: Cardiology Authors: Pil-Ki Min, Jong-Youn Kim, Kwang-Hoe Chung, Byoung Kwon Lee, Minhee Cho, Da-Lyung Lee, Sung-Yu Hong, Eui-Young Choi, Young-Won Yoon, Bum-Kee Hong, Se-Joong Rim, Hyuck Moon Kwon Tags: Imaging & Measurement of Vessel Health Source Type: research
