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This study showed no significant improvements in clinical outcomes with platelet-function monitoring and treatment adjustment for coronary stenting, as compared with standard antiplatelet therapy without monitoring. (Funded by Allies in Cardiovascular Trials Initiatives and Organized Networks and others; ARCTIC ClinicalTrials.gov number, NCT00827411.).

Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).

BACKGROUNDThe direct-acting platelet P2Y 12 receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown. METHODSWe conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. RESULTSThe median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and inhospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used. CONCLUSIONSPrehospital administration of ticagrelor in patients with acute STEMI appeared to be safe but did not improve pre-PCI coronary reperfusion. (Funded by AstraZeneca; ATLANTIC ClinicalTrials.gov number, NCT01347580.)The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITAT DE BARCELONA CRAI on January 13, 2015. For personal use only. No other uses without permission.

Objective To analyse composition of coronary thrombus in vivo, in ST-elevation Myocardial Infarction (STEMI) patients. Background The dynamic process of intracoronary thrombus formation in STEMI patients is poorly understood. Methods Intracoronary thrombi (n=45) were obtained by thromboaspiration in 288 consecutive STEMI patients presenting for primary percutaneous intervention and analyzed using high definition pictures taken with a scanning electron microscope. Plasma biomarkers (TnI, CRPus, IL-6, PAI-1, sCD40 ligand and TNF-α) and plasma fibrin clots viscoelastic properties were measured simultaneously on peripheral blood. Results Thrombi were mainly composed of fibrin (55.9±18%) with platelets (16.8±18%), erythrocytes (11.5±9%), cholesterol crystal (5.2±8.4%) and leukocytes (1.3±2.0%). The median ischemic time was 175 min [IQR 140-297]. Ischemic time impacted thrombi composition, resulting in a positive correlation with intracoronary thrombus fibrin content, r=0.38, p=0.01 and a negative correlation with platelet content r=-0.34, p=0.02. Thus, fibrin content increased with ischemic time, ranging from 48.4±21% (<3 hours) up to 66.9±9% (>6 hours) (p=0.02), while platelet content decreased from 24.9±23% (<3 hours) to 9.1±6% (>6 hours) (p=0.07). Soluble CD40 ligand was positively correlated to platelet content in the thrombus (r=0.40, p=0.02) and negatively correlated with fibrin content (r=-0.36; p=0.04). Multivariate analysis indicated that ischemic time was the only predictor of thrombus composition with a 2-fold increase of fibrin-content per ischemic hour (adjusted OR2 [1.03-3.7] p=0.01). Conclusions In acute STEMI, platelet and fibrin contents of the occlusive thrombus are highly dependent of ischemic time, which may have a direct impact on the efficacy of drugs or devices used for coronary reperfusion.

In this global meta-analysis, reduced CYP2C19 function appears to expose clopidogrel-treated patients to excess cardiovascular risk and mortality. Conflicting results among studies may be explained by differences in types and/or levels of risk of patients.

Objective-Hypofibrinolysis promotes atherosclerosis progression and recurrent ischemic events in premature coronary artery disease. We investigated the role of fibrin physical properties in this particular setting. Methods and Results-Biomarkers of recurrent thrombosis and premature coronary artery disease (CAD) were measured in 33 young post-myocardial infarction patients with angiographic-proven CAD and in 33 healthy volunteers matched for age and sex. Ex vivo plasma fibrin physical properties were assessed by measuring fibrin rigidity and fibrin morphological properties using a torsion pendulum and optical confocal microscopy. The fibrinolysis rate was derived from continuous monitoring of the viscoelastic properties after addition of lytic enzymes. Young CAD patients had a significant increase in plasma concentration of fibrinogen, von Willebrand factor, plasminogen activator inhibitor type 1, and lipoprotein(a) as compared with controls (PϽ0.05). Fibrin of young CAD patients was stiffer (Pϭ0.002), made of numerous (Pϭ0.002) and shorter fibers (Pϭ0.04), and lysed at a slower rate than that of controls (Pϭ0.03). Fibrin stiffness was an independent predictor for both premature CAD and hypofibrinolysis. Conclusions-This first detailed study of clot properties in such a group of patients demonstrated that abnormal plasma fibrin architecture is an important feature of both premature CAD and fibrinolysis rate. Key Words: acute coronary syndromes Ⅲ coagulation Ⅲ fibrinolysis Ⅲ pathophysiology Ⅲ fibrinogen Ⅲ thrombophilia T he mechanical properties of clots and their major constituent fibrin are normally finely tuned to optimize bleeding control while also minimizing their effect on atherothrombosis. 1,2 A decreased rate of fibrinolysis and increased thrombosis are generally associated with stiff clots, although such relationships are complex. 3,4 Many factors that affect clot structure have a great impact on the mechanical properties fibrin and fibrinolysis through modifications of various steps in the fibrin polymerization process and clot stabilization. 1,4,5 See page 2419Premature coronary artery disease (CAD) is associated with increased plasma levels of prothrombotic and proinflammatory biomarkers, including fibrinogen and plasminogen activator inhibitor (PAI) type 1, which are known to favor hypofibrinolysis 6 and to be independent predictors of CAD. 7,8 Epidemiological studies have also revealed a relationship between myocardial infarction (MI) and reduced permeability and increased stiffness of fibrin, especially in young post-MI patients. 9 These aspects of altered fibrin clot network architecture were not found to be attributable to classic risk factors including fibrinogen concentrations or common polymorphisms. 2 However, the relationships among premature CAD, abnormal fibrin physical properties, and hypofibrinolysis remain little explored. The lack of appropriately designed studies of the physical properties of fibrin, including simultaneous determination of viscoelastic and morphological properties o...

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