BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

• MeSH
• akutní koronární syndrom komplikace   farmakoterapie   chirurgie   MeSH
• antagonisté purinergních receptorů P2Y škodlivé účinky   terapeutické užití   MeSH
• antikoagulancia škodlivé účinky   terapeutické užití   MeSH
• Aspirin terapeutické užití   MeSH
• elektivní chirurgické výkony MeSH
• fibrilace síní komplikace   farmakoterapie   MeSH
• fibrinolytika škodlivé účinky   terapeutické užití   MeSH
• hospitalizace MeSH
• inhibitory agregace trombocytů škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární látky terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• kombinovaná terapie MeSH
• koronární angioplastika * MeSH
• krvácení chemicky indukované   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• management nemoci MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• pyrazoly terapeutické užití   MeSH
• pyridony terapeutické užití   MeSH
• senioři MeSH
• vitamin K antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.

• MeSH
• bakteriální toxiny analýza   MeSH
• jezera mikrobiologie   MeSH
• klimatické změny MeSH
• látky znečišťující vodu analýza   MeSH
• mikrocystiny analýza   MeSH
• monitorování životního prostředí MeSH
• sinice * MeSH
• teplota MeSH
• tropany analýza   MeSH
• uracil analogy a deriváty   analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. METHODS: We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. FINDINGS: 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002). INTERPRETATION: The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. FUNDING: Regado Biosciences Inc.

• MeSH
• antikoagulancia terapeutické užití   MeSH
• aptamery nukleotidové terapeutické užití   MeSH
• faktor IXa antagonisté a inhibitory   MeSH
• hirudiny MeSH
• koagulancia aplikace a dávkování   MeSH
• koronární angioplastika * MeSH
• krvácení epidemiologie   MeSH
• léková alergie epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oligonukleotidy aplikace a dávkování   MeSH
• peptidové fragmenty terapeutické užití   MeSH
• předčasné ukončení klinických zkoušek MeSH
• rekombinantní proteiny terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH
• Severní Amerika MeSH

AIMS: Patient access to reperfusion therapy and the use of primary percutaneous coronary intervention (p-PCI) or thrombolysis (TL) varies considerably between European countries. The aim of this study was to obtain a realistic contemporary picture of how patients with ST elevation myocardial infarction (STEMI) are treated in different European countries. METHODS AND RESULTS: The chairpersons of the national working groups/societies of interventional cardiology in European countries and selected experts known to be involved in the national registries joined the writing group upon invitation. Data were collected about the country and any existing national STEMI or PCI registries, about STEMI epidemiology, and treatment in each given country and about PCI and p-PCI centres and procedures in each country. Results from the national and/or regional registries in 30 countries were included in this analysis. The annual incidence of hospital admission for any acute myocardial infarction (AMI) varied between 90-312/100 thousand/year, the incidence of STEMI alone ranging from 44 to 142. Primary PCI was the dominant reperfusion strategy in 16 countries and TL in 8 countries. The use of a p-PCI strategy varied between 5 and 92% (of all STEMI patients) and the use of TL between 0 and 55%. Any reperfusion treatment (p-PCI or TL) was used in 37-93% of STEMI patients. Significantly less reperfusion therapy was used in those countries where TL was the dominant strategy. The number of p-PCI procedures per million per year varied among countries between 20 and 970. The mean population served by a single p-PCI centre varied between 0.3 and 7.4 million inhabitants. In those countries offering p-PCI services to the majority of their STEMI patients, this population varied between 0.3 and 1.1 million per centre. In-hospital mortality of all consecutive STEMI patients varied between 4.2 and 13.5%, for patients treated by TL between 3.5 and 14% and for patients treated by p-PCI between 2.7 and 8%. The time reported from symptom onset to the first medical contact (FMC) varied between 60 and 210 min, FMC-needle time for TL between 30 and 110 min, and FMC-balloon time for p-PCI between 60 and 177 min. CONCLUSION: Most North, West, and Central European countries used p-PCI for the majority of their STEMI patients. The lack of organized p-PCI networks was associated with fewer patients overall receiving some form of reperfusion therapy.

• MeSH
• balónková koronární angioplastika statistika a číselné údaje   MeSH
• časové faktory MeSH
• charakteristiky bydlení MeSH
• dostupnost zdravotnických služeb MeSH
• hospitalizace statistika a číselné údaje   MeSH
• incidence MeSH
• infarkt myokardu epidemiologie   terapie   MeSH
• lidé MeSH
• mortalita v nemocnicích MeSH
• odhad potřeb MeSH
• reperfuze myokardu metody   statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH