The atlas acs 2 timi 51 trial highlights the potential impact of missing data on precluding definitive causal inferences in premarketing registration trials. Rationale and design of the antixa therapy to lower. An efficacy and safety study for rivaroxaban in patients. Autoantibodies to phosphorylcholine and cardiovascular. Baseline characteristics of patients on a background of aspirin monotherapy. Pdf acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Fda briefing document for the cardiovascular and renal drugs advisory committee crdac meeting date. Rationale and design of the antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndromethrombolysis in myocardial infarction 51 atlas acs 2 timi 51 trial. Atlas acs timi 46 were included through the end of study, and events from atlas acs 2 timi 51 were included if they table 1. The appraise, appraisej, rivaroxaban versus placebo in patients with acute coronary syndromes atlas acs timi 46, and dose finding study for dabigatran etexilate in patients with acute coronary syndrome redeem clinical trials reported 6month followup outcomes, 12,15,18 while appraise 2 and atlas acs 2 timi 51 reported 8month and. Krantz, md,yz sanjay kaul, mdxk aurora and denver, colorado.
Atlas acs 2timi 51 was a phase iii, multicenter, randomized, doubleblind, placebocontrolled clinical trial evaluating an oral, direct factor xa inhibitor rivaroxaban in subjects following an acute coronary syndrome. Timi 46 trial were included if they had occurred after randomization, through. Rivaroxaban versus placebo in patients with acute coronary. The study delivered improved outcomes for acs patients through a dual pathway treatment strategy combining xarelto and standard antiplatelet therapy, compared to standard antiplatelet therapy alone. Estudios con rivaroxaban edad atlas acs timi 46 57. L oppenheimer, c m gibson, on behalf of the atlas acs timi 46 study group summary background rivaroxaban is an oral direct factor xa inhibitor that has been e. Rivaroxaban was tested at total daily doses ranging from 5 to 20 mg and, as compared with pla. Phase iiiphase iii the pivotal atlas acs 2timi 51 study. Atlas acs timi 46 trial and antithrombotic therapy with dr mike gibson. Direct oral anticoagulants in addition to antiplatelet. Rivaroxaban in patients with a recent acute coronary syndrome article pdf available in new england journal of medicine 3661.
Background rivaroxaban is an oral direct factor xa. The atlas acs timi 46 antixa therapy to lower cardiovascular events in addition to aspirin with or without thienopyridine therapy in subjects with acute coronary syndrome thrombolysis in myocardial infarction 46 trial was designed to address these questions. The atlas acs 2timi 51 trial and the burden of missing data. Request pdf rivaroxaban versus placebo in patients with acute coronary syndromes atlas acs timi 46. The atlas acs timi 46 trial assessed the safety and efficacy of rivaroxaban compared with placebo in acs patients. Atlas acs timi 46 compared the safety and efficacy of rivaroxaban, an oral direct factor xa inhibitor, to placebo in patients with acute coronary syndromes. The phase ii randomized, placebocontrolled, dosefinding atlas acs timi 46 trial clinicaltrials. Additionally in the complete response letter, the sponsor was asked to address the following. Antixa therapy to lower cardiovascular events in addition. Results of the atlas acstimi 46 study published in the. Rivaroxaban in acute coronary syndromes is it prime time. Autoantibodies to phosphorylcholine and cardiovascular outcomes in patients with acute coronary syndromes in the atlas acs timi 46 trial. The atlas study programme enrolled more than 19,000 patients.
We investigated the relationship of antipc concentrations with cardiovascular outcomes in patients with acute coronary syndromes acs. Atlas acs 2 timi 51 was a phase iii, multicenter, randomized, doubleblind, placebocontrolled clinical trial evaluating an oral, direct factor xa inhibitor rivaroxaban in subjects following an acute coronary syndrome. Provide a description of your plans to develop a lower strength formulation to be used for. Rivaroxaban in combination with aspirin alone or with aspirin and a thienopyridine in patients with acute coronary syndromes the atlas acs timi 46 trial the safety and scientific validity of this study is the responsibility of the.
Rivaroxaban is the only novel oral anticoagulant oac that has finalised a phase iii clinical trial in acute coronary syndrome acs with a. Results of the highly anticipated atlas acs 2 timi 51 demonstrate that acs patients receiving standard therapy, including dual antiplatelet therapy, may benefit from the addition of the factor. For this study, data from all published phase ii and iii studies seven in total of new oral anticoagulants after a recent acs were included the esteem, 11 redeem, 14 ruby1, 15 appraise1 12 and appraise2, 16 atlas acs timi 46, and atlas acs 2 timi 51 17 studies, irrespective of other study or report characteristics. Design the second atlasacs 2 timi 51 trial is an international. Rivaroxaban in patients with a recent acute coronary syndrome. The atlas acs 2 timi 51 trial and the burden of missing data.
The antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndromethrombolysis in myocardial infarction 51 atlas acs 2 timi 51 study randomized 15,526 patients with a recent acs to rivaroxaban 2. Ddimer levels and effect of rivaroxaban on those levels. The effect of rivaroxaban on myocardial infarction in the. Barnathan es, bordes p, witkowski a, markov v, oppenheimer l, gibson cm, atlas acs timi 46 study group. Rivaroxaban versus placebo in patients with acute coronary syndromes atlas acs timi 46. A randomized, doubleblind, phase ii trial rivaroxaban is an oral direct factor xa. The results of the atlas acs timi 46 trial indicate that rivaroxaban, an oral factor xa inhibitor, is associated with reasonable efficacy compared with placebo for triple therapy in patients presenting with acs, with a higher risk of clinically significant bleeding. The phase ii atlas acs timi 46 trial noted that in patients with recent acute coronary syndrome acs, rivaroxaban, on a background of dual antiplatelet therapy with aspirin and clopidogrel, was associated with reasonable efficacy but increased bleeding as compared with placebo. The pivotal atlas acs 2 timi 51 study proves xarelto 2.
The primary with acs trial was a doubleblind phase ii trial of rivaroxaban in efficacy outcome was the composite end. Whether triple antithrombotic therapy with novel anticoagulants, such as rivaroxaban, for acs will. A phase ii dosefinding study as a phase ii dosefinding study, atlas acs timi 46 trial was designed to explore the safety and efficacy of rivaroxaban at escalating total daily doses, ranging from 5 mg up to. The atlas acs timi 46 trial a combination with aspirin alone or with aspirin and a thienopyridine ntixa therapy to lower cardiovascular events in addition to. Summary the atlas acs 2 timi 51 is testing the hypothesis that anticoagulation with the oral factor xa inhibitor rivaroxaban reduces cardiovascular death, mi, and stroke among patients with acs treated with guidelinebased therapies for acs. Background among patients with acute coronary syndrome acs. Original article from the new england journal of medicine rivaroxaban in patients with a recent acute coronary syndrome. Provide a final report for the atlas acs timi 46 study, including electronic datasets sufficient to verify the safety and efficacy data. We measured antipc levels within 7 days of an acs in 3,356 patients enrolled in the atlas acs timi 46 trial, a randomized dose ranging study of rivaroxaban versus placebo. To assess the safety and efficacy of rivaroxaban in patients after an acute coronary syndrome, the atlas acs timi 46 antixa therapy to lower cardiovascular events in addition to aspirin with or without thienopyridine therapy in subjects with acute coronary syndromethrombolysis in myocardial infarction 46 trial was undertaken. Rivaroxaban in combination with aspirin alone or with. New oral anticoagulants in addition to single or dual.
Fda briefing document for the cardiovascular and renal. Geller bj, mega jl, morrow da, guo j, hoffman eb, gibson cm, ruff ct. Atlas acs timi 46 was a phase 2 study, and the goal was to select an appropriate dose to be carried forward into the phase 3 study, mega told heartwire. On september 6, 2012, the sponsor submitted to the fda important data related to patients who had withdrawn from the atlas acs 2 timi 51 trial as part of its complete response. Therefore, our study, in conjunction with the important observations from appraise2, atlas acs timi 46, and ruby1 suggests that in patients with a. It was hypothesized that elevated baseline ddimer would be associated with poor clinical outcomes in acs, and that factor xa inhibition with rivaroxaban would reduce ddimer acutely and chronically. The atlas acs 2 timi 51 trial and the burden of missing data antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome acs 2thrombolysis in myocardial infarction 51 mori j. Antithrombotic therapy in patients with recent acs. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. An efficacy and safety study for rivaroxaban in patients with acute coronary syndrome. The atlas acs 2timi 51 trial and the burden of missing data core. Atlas acstimi 46 compared the safety and efficacy of rivaroxaban, an oral direct factor xa inhibitor, to placebo in patients with acute coronary syndromes. Influence of modelpredicted rivaroxaban exposure and. Pooled atlas acs timi 46 and atlas acs 2 timi 51 characteristics atlas acs timi 46 n427 atlas acs 2 timi 51 n1050 combined n1477 combined.
L oppenheimer, c m gibson, on behalf of the atlas acstimi 46 study group. Rivaroxaban versus placebo in patients with acute coronary syndromes atlas acstimi 46. The atlas acs 2timi 51 trial and the burden of missing. The safety of direct oral anticoagulants with p2y12. Following an acute coronary syndrome event patients are at risk of important additional clinical events such as death, myocardial infarction, and stroke.
Antixa therapy to lower cardiovascular events in addition to aspirin with or without thienopyridine therapy in subjects with acute coronary syndrome thrombolysis in myocardial infarction 46 trial 2009 condition. Safety and efficacy of rivaroxaban when added to aspirin. The atlas acs 2timi 51 study multivu, a cision company. Therefore, our study, in conjunction with the important observations from appraise2, atlas acs timi 46, and ruby1 suggests that in patients with a recent acute coronary syndrome, very low doses. Placebo5176 patients were randomly assigned in a 1. Acute coronary syndrome acs is a serious and life threatening condition. The results of the atlas acs 2 timi 51 study showed that both 2. Timi 51 to evaluate the strategy of combining rivaroxaban with aspirin compared with treatment with aspirin alone in the period immediately following an acute coronary syndrome. We included seven clinical trials atlas acs timi 46, appraise, appraise2, redeem, atlas acs timi 51, appraisej, and geminiacs1 to assess the safety of adding a doac to antiplatelet therapy compared to the standard of care dapt in patients with acs. It is an umbrella term for the clinical study programme of rivaroxaban in the secondary prevention of acute coronary syndrome acs.
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