Trial reportEuropean heart journal2009
Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists.
Trial report in European heart journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00684307 (A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation), which is not on this map. Cited by 20 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
Who cites it
20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Measures of vitamin K antagonist control reported in atrial fibrillation and venous thromboembolism studies: a systematic review.BMJ open · 2014Pooled it
- Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation.The Cochrane database of systematic reviews · 2014Pooled it
- Major bleeding in patients with atrial fibrillation receiving vitamin K antagonists: a systematic review of randomized and observational studies.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2013Pooled it
- Exposure-response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation.British journal of clinical pharmacology · 2015Trial
- Reversible elevations of serum creatinine levels but no effect on glomerular filtration during treatment with the direct thrombin inhibitor AZD0837.European journal of clinical pharmacology · 2010Trial
- Effects of AZD0837, a novel direct thrombin inhibitor, on the electrophysiological properties of the human heart: a randomized, double-blind, parallel-group, placebo-controlled study.Clinical drug investigation · 2010Trial
- Cost-effectiveness of anticoagulation in patients with nonvalvular atrial fibrillation with edoxaban compared to warfarin in Germany.BioMed research international · 2015Article
- Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework.Nature reviews. Drug discovery · 2014Review
- Oral anticoagulants for Asian patients with atrial fibrillation.Nature reviews. Cardiology · 2014Review
- Cardiovascular outcomes during treatment with dabigatran: comprehensive analysis of individual subject data by treatment.Vascular health and risk management · 2013Review
- Anticoagulant therapy for patients with ischaemic stroke.Nature reviews. Neurology · 2012Review
- Review of atrial fibrillation outcome trials of oral anticoagulant and antiplatelet agents.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2012Review
- Review
- A semi-mechanistic modeling strategy for characterization of regional absorption properties and prospective prediction of plasma concentrations following administration of new modified release formulations.Pharmaceutical research · 2012Article
- Deficiency of NG2+ cells contributes to the susceptibility of stroke-prone spontaneously hypertensive rats.CNS neuroscience & therapeutics · 2011Article
- Update on anti-coagulation in atrial fibrillation.QJM : monthly journal of the Association of Physicians · 2011Review
- Stroke prevention treatment of patients with atrial fibrillation: old and new.Current neurology and neuroscience reports · 2011Review
- New options in anticoagulation for the prevention of venous thromboembolism and stroke.P & T : a peer-reviewed journal for formulary management · 2011Article
- Article
- Stroke Prevention in Atrial Fibrillation.Journal of atrial fibrillationReview
Corrections and comments
- Commented on by
Authors and funding
8 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsOral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. METHODS AND
resultsAtrial fibrillation patients (n = 955) with > or =1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naïve to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). d-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naïve subjects with treatment, whereas in VKA pre-treated patients, d-dimer levels started low and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by approximately 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase > or =3x upper limit of normal was similar for AZD0837 and VKA.
conclusionAZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA. This study is registered with ClinicalTrials.gov, number NCT00684307.
Indexed as
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.