Journal of thrombosis and haemostasis : JTH
-
J. Thromb. Haemost. · Jun 2016
Multicenter Study Observational StudyContemporary antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: 1-year outcomes from the GReek AntiPlatElet (GRAPE) Registry.
Essentials The comparative efficacy and safety of antiplatelet agents in 'real life' is not clear. We recruited acute coronary syndrome patients receiving percutaneous coronary intervention. At 1-year follow-up, prasugrel offers better anti-ischemic protection than clopidogrel. Prasugrel and ticagrelor are accompanied by more frequent bleeding events. ⋯ Background The comparative efficacy and safety of antiplatelet treatment outside randomized trials is not clear. Objectives To investigate long-term efficacy and safety in 'real-life' acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with contemporary use of clopidogrel, prasugrel and ticagrelor. Methods In a prospective, observational, multicenter cohort study, 2047 patients were recruited into the GReek AntiPlatElet (GRAPE) Registry and were followed-up for 1 year for major adverse cardiovascular events (MACE, a composite of death, non-fatal myocardial infarction, urgent revascularization and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification). Results Exposure to clopidogrel, prasugrel and ticagrelor by PCI occurred in 959, 363 and 717 patients, respectively. After adjustment, the rate of MACE (primary outcome endpoint) was lower in prasugrel-treated patients (4.4%) than in clopidogrel-treated patients (10.1%) (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.30-0.91), although not significantly different between ticagrelor (6.8%) and clopidogrel groups (HR, 0.78; 95% CI, 0.54-1.12). Any type of BARC-classified bleeding (secondary outcome endpoint) was more frequent in prasugrel-treated patients (51.2%) than in clopidogrel-treated patients (37.6%) (HR, 1.61; 95% CI, 1.33-1.95) and more frequent in ticagrelor-treated patients (56.9%) than in clopidogrel-treated patients (HR, 1.81; 95% CI, 1.55-2.10). An adjusted comparison between prasugrel and ticagrelor-treated groups did not reveal differences in any outcome measure. After adjustment, the death rate was more reduced by novel agents in comparison with clopidogrel (2.9% vs. 6.2%). Conclusions In ACS/PCI patients, prasugrel offered better anti-ischemic protection than clopidogrel, whereas use of both novel agents is accompanied by more frequent bleeding events.
-
J. Thromb. Haemost. · Jun 2016
Impact of incident myocardial infarction on the risk of venous thromboembolism: the Tromsø Study.
Essentials Registry-based studies indicate a link between arterial- and venous thromboembolism (VTE). We studied this association in a cohort with confounder information and validated outcomes. Myocardial infarction (MI) was associated with a 4.8-fold increased short-term risk of VTE. MI was associated with a transient increased risk of VTE, and pulmonary embolism in particular. ⋯ Background Recent studies have demonstrated an association between venous thromboembolism (VTE) and arterial thrombotic diseases. Objectives To study the association between incident myocardial infarction (MI) and VTE in a prospective population-based cohort. Methods Study participants (n = 29 506) were recruited from three surveys of the Tromsø Study (conducted in 1994-1995, 2001-2002, and 2007-2008) and followed up to 2010. All incident MI and VTE events during follow-up were recorded. Cox regression models with age as the time scale and MI as a time-dependent variable were used to calculate hazard ratios (HRs) of VTE adjusted for sex, body mass index, blood pressure, diabetes mellitus, HDL cholesterol, smoking, physical activity, and education level. Results During a median follow-up of 15.7 years, 1853 participants experienced an MI and 699 experienced a VTE. MI was associated with a 51% increased risk of VTE (HR 1.51; 95% confidence interval [CI] 1.08-2.10) and a 72% increased risk of pulmonary embolism (PE) (HR 1.72; 95% CI 1.07-2.75), but not significantly associated with the risk of deep vein thrombosis (DVT) (HR 1.36; 95% CI 0.86-2.15). The highest risk estimates for PE were observed during the first 6 months after the MI (HR 8.49; 95% CI 4.00-18.77). MI explained 6.2% of the PEs in the population (population attributable risk) and 78.5% of the PE risk in MI patients (attributable risk). Conclusions Our findings indicate that MI is associated with a transient increased VTE risk, independently of traditional atherosclerotic risk factors. The risk estimates were particularly high for PE.
-
J. Thromb. Haemost. · Jun 2016
Platelets are dispensable for antibody-mediated transfusion-related acute lung injury in the mouse.
Essentials Role of platelets in immunological transfusion-related acute lung injury (TRALI) is debated. Immunological TRALI was tested in mice exhibiting severe thrombocytopenia or platelet dysfunction. Platelets are required to prevent lung hemorrhage but not edema formation and respiratory distress. Platelets are dispensable for the initiation and development of TRALI. ⋯ Background Transfusion-related acute lung injury (TRALI) is a serious transfusion-related complication. Previous conflicting studies have indicated that platelets are either crucial or dispensable for TRALI. Objectives To evaluate the role of platelets in major histocompatibility complex (MHC) I-induced-TRALI. Methods Antibody-mediated TRALI was experimentally induced in mice by lipopolysaccharide priming followed by the administration of an anti-MHC I mAb. Results TRALI was tested in the context of severe thrombocytopenia provoked by the administration of diphtheria toxin (DT) in transgenic iDTR mice selectively expressing DT receptor in megakaryocytes. The pathologic responses occurring within the first 10 min following the injection of the anti-MHC I mAb, i.e. the severity of lung edema and the drop in aortic blood oxygenation, were similar in severely thrombocytopenic DT-iDTR and control mice. At later times, mortality was nevertheless increased in DT-iDTR mice, owing to lung hemorrhages. When less severe thrombocytopenia was induced with an antiplatelet mAb, TRALI started and developed similarly as in control mice, but hemorrhages were absent. Furthermore, when platelet functions were defective because of administration of aspirin or clopidogrel, or because of glycoprotein (GP)IIbIIIa deficiency, TRALI still developed but no lung hemorrhages were observed. In contrast, when GPVI was immunodepleted, TRALI still occurred, but was occasionally accompanied by hemorrhages. Conclusions Platelets are dispensable for the initiation and development of MHC I-induced TRALI. Although they do not protect against the disruption of the vascular endothelial cell barrier and the subsequent plasma leakage and edema formation, platelets are essential to prevent more serious damage resulting in hemorrhages in alveoli.