Xa 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 and atlas acs 2. 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. The phase 2 programs, which evaluated rivaroxaban, apixaban, dabigatran, and darexaban, all showed a dosedependent increase in bleeding. Recent acute coronary syndrome the atlas acs 2 timi 51 trial the second trial of a ntixa t herapy to l ower cardiovascular events in a ddition to standard therapy in s ubjects with. Request pdf rivaroxaban versus placebo in patients with acute coronary syndromes atlas acstimi 46. L oppenheimer, c m gibson, on behalf of the atlas acstimi 46 study group. Estudios con rivaroxaban edad atlas acs timi 46 57. 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. 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. The atlas acs 2 timi 51 trial investigated rivaroxaban 2. The primary objective of the atlasacs 2 timi 51 study is to. Fda briefing document for the cardiovascular and renal.
Nov, 2011 results of the highly anticipated atlasacs 2timi 51 demonstrate that acs patients receiving standard therapy, including dual antiplatelet therapy, may benefit from the addition of the factor xa inhibitor rivaroxaban, although at the cost of some additional bleeding complications. In the atlas acs 2timi 51 trial, 2,402 patients 15. A univariate and multivariable logistic regression assessed the relation between baseline ddimer and a composite end point of cardiovascular death. Subjects received lowdose aspirin therapy 75 to 100 mgday, and enrollment was stratified based upon. 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. The atlas acs timi 46 antixa therapy to lower cardiovascular events in addition to aspiron with or without thienopyridine treatment in subjects with acute. Modes and timing of death in 66 252 patients with nonst.
Mega jl, braunwald e, mohanavelu s, burton p, poulter r, misselwitz f, atlas acs timi 46 study group et al. To explore efficacy of rivaroxaban at tolerable doses conduct a robust phase ii dose ranging trial gibson cm, aha 2008. The ones marked may be different from the article in the profile. A subset of subjects had a ddimer measured at baseline n 1,834, 52. An efficacy and safety study for rivaroxaban in patients with.
A total of 1477 patients were analyzed in a pooled analysis of subsets of the atlas acs. Characterising and predicting bleeding in highrisk patients. An efficacy and safety study for rivaroxaban in patients. Antithrombotic therapy in patients with recent acs.
Ddimer levels and effect of rivaroxaban on those levels. Efficacy and safety of adding rivaroxaban to the anti. It is available for cavities ranging between 60mm and 150mm and can also fix back to a number of structures using the atlas range of fixings. Table 1 the atlas acs 2timi 51 trial and the burden of. Atlas acs 2 timi 51 antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome acs 2thrombolysis in myocardial infarction 51. The incidence of bleeding was highest in the immediate post acs period 0. Results the proportion of patients who experienced timi major or minor, isth major or crnm, and any bleeding was 1. Atlas acs timi 46 rates of clinically significant bleeding 143 table 51. Published atlas acstimi 46 results for rivaroxaban pave. A dosefinding phase 2 study atlas, timi 46 demonstrated benefit with respect to the primary composite endpoint but also showed increased bleeding with higher rivaroxaban doses. Oct 31, 2012 remark substantial progress has occurred in modelling the likelihood of ably, however, when tested in much lower doses i. An overview of prove it timi 22 a comparison of intensive statin therapy and moderate statin therapy in acute coronary syndrome patients. Results from the atlas acs 2 timi 51 study showed that both 2.
All dose groups completed enrolment, without premature cessation, and by the end of the study a discernible dosedependent increase in clinically significant bleeding was detected. Nov, 2011 results from the atlas acs 2 timi 51 study showed that both 2. The effect of rivaroxaban on myocardial infarction in the. Secondary prevention of acute coronary syndrome phase ii for more information about the xarelto clinical development program, please refer to the about xarelto clinical studies backgrounder or. Please see the table in the product details section for more details. The second trial of antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndromes. Atlas acs timi 46 was designed as a doseescalation study to assess the safety profile of different rivaroxaban dosing regimens. New oral anticoagulants in addition to single or dual. The atlas acs 2timi 51 trial and the burden of missing data. Safety and efficacy of rivaroxaban when added to aspirin. The safety of direct oral anticoagulants with p2y12.
After a mean of months of followup, both doses significantly reduced the composite of cardiovascular death, myocardial infarction and stroke. In line with the results on dabigatran and apixaban, rivaroxaban led to a. The apparent dichotomy between the results of appraise 2 and atlas acs is informed by at least two factors. Atlas acstimi 46 compared the safety and efficacy of rivaroxaban, an oral direct factor xa inhibitor, to placebo in patients with acute coronary syndromes. Direct oral anticoagulants in addition to antiplatelet. Timi 51 investigated the efficacy and safety of rivaroxaban among men and women, more than 18 years of age, who were stabilized post. Adding rivaroxaban to antiplatelet therapy reduced. Acute myocardial infarction in patients with st segment. Very lowdose direct oral anticoagulants combined with. 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. Dec 17, 2008 an efficacy and safety study for rivaroxaban in patients with acute coronary syndrome the safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
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. 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. Rivaroxaban in patients with a recent acute coronary syndrome.
Rivaroxaban was tested at total daily doses ranging from 5 to 20 mg and, as compared with pla. 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. 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. Chronic coronary artery disease cad and peripheral artery disease pad are common manifestations of atherosclerosis. The atlas acs timi 46 trial assessed the safety and efficacy of rivaroxaban compared with placebo in acs patients. 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. Rivaroxiban versus placebo in patients with acute coronary syndromes atlas acs timi 46. Atlas acs2timi51 was a randomized, doubleblind, placebocontrolled, eventdriven trial that included 15,526 patients. Dec 19, 20 indice introduccion riesgo residual, riva estudios atlas 1 timi 51 y atlas 2 subgrupo stemi repercusiones aprobacion, guias, prensa conclusiones 11. Barnathan es, bordes p, witkowski a, markov v, oppenheimer l, gibson cm, atlas acs timi 46 study group.
Values are n % or hazard ratio 95% confidence interval. Forest plot for the primary efficacy end point for atlas acs timi 46, atlas acs 2 timi 51, and both trials combined. Prove it timi 22 trial overview1 a multicenter randomized treatmentcontrolled trial to determine lipid lowering effects of high dose atorvastatin vs. Promise of factor xa inhibition in acute coronary syndromes. Fda briefing document for the cardiovascular and renal drugs. Rivaroxaban versus placebo in patients with acute coronary. Therefore, on the basis of this biology and the findings of this study, treatment with rivaroxaban might be a useful adjunctive therapy in patients who are stabilised after an acute coronary syndrome. Gibson cm, mega jl, burton p, goto s, verheugt f, bode c, plotnikov a, sun x, cookbruns n, braunwald e. Rationale and design of the antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome thrombolysis in myocardial infarction 51 atlas acs 2 timi 51 trial. Listing a study does not mean it has been evaluated by the u. 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. In this setting, we assessed the safety and efficacy of rivaroxaban and. Atlas acs 2timi 51 rivaroxaban xarelto stemi study.
This cited by count includes citations to the following articles in scholar. Mega jl, braunwald e, mohanavelu s burton p, poulter r, misselwitz f, hricak v, barnathan es, bordes p, witkowski a, markov v, oppenheimer l, gibson cm. It compared daily doses of 5 to 20 mg given either once or twice daily in patients stratified by either concomitant sapt aspirin or dapt aspirin with a thienopyridine. To identify tolerable doses of rivaroxaban in the treatment of acs for evaluation in a large phase iii trial timi 46 atlas secondary goal efficacy. Rivaroxaban in patients stabilized after a stsegment. P values are based on the unstratified log rank test and hr 95% ci are based. Rationale and design of the antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome thrombolysis in myocardial infarction 51 atlas acs 2timi 51 trial. In the recent phase iii atlas acs 2 timi 51 trial, rivaroxaban 2. Atlas acs 2timi 51 rivaroxaban xarelto stemi study published. Rivaroxaban in combination with aspirin alone or with aspirin and a thienopyridine in patients with acute coronary syndromes. Nonstsegment elevation acute coronary syndromes nste acs now represent a greater proportion of acute coronary syndrome acs events than stsegment elevation myocardial infarctions stemi. Antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome thrombolysis in myocardial infarction 51 b.
Background rivaroxaban is an oral direct factor xa. The atlas acs 2 timi 51 trial the second trial of antixa therapy to l ower cardiovascular events in a ddition to standard therapy in s ubjects with a cute c oronary s yndrome. The new oral anticoagulants blood american society of. Rivaroxaban was investigated in the setting of acs within the phase ii antixa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndromes thrombolysis in myocardial infarction atlas acs timi 46 trial. Dec 08, 2012 atlas acs timi 46 was a phase 2 trial that randomized 3491 patients after acs to receive either placebo or rivaroxaban at total daily doses of 5, 10, 15, or 20 mg, administered either qd or bid. Applying the spectrum of antithrombotic therapies to your. Rivaroxaban in patients with a recent acute coronary syndrome article pdf available in new england journal of medicine 3661. Baseline characteristics of patients on a background of aspirin monotherapy. The atlas 10 masonry support systems design supports a masonry load up to 10knm. Atlas acs timi 46 was the dosefinding phase ii trial for rivaroxaban in acs patients 12. 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. Nonvitamin k antagonist oral anticoagulant icr journal. Advances in the treatment of stable coronary artery disease. Article pdf available in new england journal of medicine 3661.
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