A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease

BACKGROUND Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease.METHODS We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [ no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses.RESULTS At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P = 0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P = 0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P< 0.001 for noninferiority, P = 0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P = 0.01 for noninferiority, P = 0.10 for superiority).CONCLUSIONS In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776.

The Pierre Auger Observatory scaler mode for the study of solar activity modulation of galactic cosmic rays

Since data-taking began in January 2004, the Pierre Auger Observatory has been recording the count rates of low energy secondary cosmic ray particles for the self-calibration of the ground detectors of its surface detector array. After correcting for atmospheric effects, modulations of galactic cosmic rays due to solar activity and transient events are observed. Temporal variations related with the activity of the heliosphere can be determined with high accuracy due to the high total count rates. In this study, the available data are presented together with an analysis focused on the observation of Forbush decreases, where a strong correlation with neutron monitor data is found.Comision Nacional de Energia Atomica, ArgentinaFundacion AntorchasGobierno De La Provincia de Mendoza, Municipalidad de Malargue, ArgentinaNDM HoldingsValle Las Lenas, ArgentinaAustralian Research Council (ARC)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Ministério da Ciência, Tecnologia e Inovação do Brasil (MCTI)Academy of Sciences of the Czech Republic (AVCR) [AV0Z10100502] [AV0Z10100522] [GAAV KJB300100801] [KJB100100904] [MSMT-CR LA08016] [LC527] [1M06002] [MSM0021620859]Centre National de la Recherche Scientifique (CNRS), Centre de Calcul IN2P3/CNRSConseil Regional Ile-de-France, Departement Physique Nucleaire et Corpusculaire [PNC-IN2P3/CNRS]Departement Sciences de l`Univers (SDU-INSU/CNRS), FranceBundesministerium fur Bildung und Forschung (BMBF)Deutsche Forschungsgemeinschaft (DFG)Finanzministerium Baden-WurttembergHelmholtz-Gemeinschaft Deutscher Forschungszentren (HGF)Ministerium fur Wissenschaft und Forschung, Nordrhein-Westfalen, GermanyMinisterium fur Wissenschaft, Forschung und Kunst, Baden-Wurttemberg, GermanyIstituto Nazionale di Fisica Nucleare (INFN)Istituto Nazionale di Astrofisica (INAF)Ministero dell Istruzione, dell Universita e della Ricerca (MIUR), ItalyConsejo Nacional de Ciencia y Tecnologia (CONACYT), MexicoMinisterie van Onderwijs, Cultuur en Wetenschap, Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)Stichting voor Fundamenteel Onderzoek der Materie (FOM), NetherlandsMinistry of Science and Higher Education, Poland [1 P03 D 014 30] [N N202 207238]Fundacao para a Ciencia e a Tecnologia (FCT), PortugalMinistry for Higher Education, Science, and Technology, Slovenian Research Agency, SloveniaComunidad de Madrid, SpainConsejeria de Educacion de la Comunidad de Castilla La ManchaFondo Europeo de Desarrollo Regional (FEDER)Ministerio de Ciencia e Innovacion, Consolider-Ingenio, SpainGeneralitat ValencianaJunta de AndaluciaXunta de Galicia, SpainScience and Technology Facilities Council, United KingdomU.S. Department of Energy (DOE) [DE-AC02-07CH11359] [DE-FR02-04ER41300]National Science Foundation (NSF) [0450696]Grainger Foundation USAALFA-EC / HELENEuropean Union [MEIF-CT-2005-025057] [PIEF-GA-2008-220240]United Nations Educational, Scientific and Cultural Organization (UNESCO

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients