Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial

Mega, J. L.; Braunwald, Eugene; Mohanavelu, Satishkumar; Burton, Paul; Poulter, Rohan; Misselwitz, Frank; Hricak, V.; Barnathan, ES; Bordes, Pascual; Witkowski, Adam; Марков, В. А.; Oppenheimer, Leonard; Gibson, C. Michael

doi:10.1016/s0140-6736(09)60738-8

Cited by 634 publications

(473 citation statements)

References 21 publications

Supporting

Mentioning

434

Contrasting

Unclassified

Order By: Relevance

“…Several trials have attempted to add an oral anticoagulant to DAPT in the post-acute coronary syndromes setting leveraging a triple antithrombotic therapy approach. Although the ATLAS ACS-2 trial 19 with the same low-dose of rivaroxaban studied in GEMINI-ACS-1 showed a significant reduction in the risk of the composite outcome of cardiovascular death, myocardial infarction, and stroke and in the risk of all-cause death, the rate of major bleeding was three-fold to four-fold higher when rivaroxaban was added to aspirin and clopidogrel in the post-acute coronary syndromes setting. 11 A similar trial (APPRAISE-2) 12 assessing the standard dose of apixaban (used for the treatment of atrial fibrillation) plus DAPT in the post-acute coronary syndromes setting was prematurely terminated due to an excessive risk of intracranial haemorrhage and major bleeding with triple antithrombotic therapy, with no difference in the risk of recurrent ischaemic events.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial

et al. 2017

View full text Add to dashboard Cite

SummaryBackground Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months.

show abstract

Section: Discussionmentioning

confidence: 97%

“…17 We aimed to investigate the safety of this novel dual pathway antithrombotic regimen using clinically significant bleeding as a measure of antithrombotic therapy potency. 18,19 …”

Section: Introductionmentioning

confidence: 99%

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The control arms in the reported trials, against which TT was compared, have mostly included patients receiving a combination of aspirin and clopidogrel,21, 22, 23, 28, 29, 30, 31, 45 but current guidelines recommend ticagrelor or prasugrel over clopidogrel in ACS 15, 20, 26, 38. Consequently, any new combination regimen should be compared with “current best.” The combination of a non–vitamin K oral anticoagulant with DAPT that includes these more effective P2Y 12 inhibitors may increase bleeding compared with clopidogrel, but this has never been tested.…”

Section: Discussionmentioning

confidence: 99%

“…The dose‐finding, phase II, ATLAS ACS‐TIMI 46 (Anti‐Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction 46)23 study assessed the safety and efficacy of the direct oral FXa inhibitor rivaroxaban (5, 10, 15, or 20 mg once or twice daily) in addition to DAPT (with clopidogrel) or single antiplatelet therapy with low‐dose aspirin in 3941 patients with recent ACS. Bleeding complications increased in a dose‐dependent manner in all TT groups ( P< 0.0001).…”

Section: Beyond Dapt: Triple‐therapy Combinations In Acsmentioning

confidence: 99%

More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy—Current Data and Future Directions

Spinthakis

Farag

Rocca

et al. 2018

JAHA

View full text Add to dashboard Cite

“…Rivaroxaban (Xarelto ® ) Approved [14] Approved [15] Approved [7] Improved survival [16] Not yet approved Dabigatron (Pradaxa ® ) Approved [17] Approved [18] Approved [6] No benefit Trend toward increased myocardial infarction Trial halted DVT, deep vein thrombosis; Afib, atrial fibrillation; ACS, acute coronary syndrome.…”

Section: Dvt Prevention Dvt Treatment Afib Acsmentioning

confidence: 99%

What did we learn from new oral anticoagulant treatment?

Esmon¹

2012

Thrombosis Research

View full text Add to dashboard Cite

Orally active direct inhibitors of thrombin and factor Xa have now been approved for treatment or prevention of deep vein thrombosis, and stroke associated with atrial fibrillation. The factor Xa inhibitor, rivaroxaban, has shown promising results in the treatment of acute coronary syndrome but is not yet approved for that indication. These agents share a rapid onset and are cleared with half lives of approximately 10 hours. At present there is no approved antidote for either class of anticoagulant, making the treatment of life-threatening bleeding episodes problematic. These agents have fewer drug interactions than warfarin, have a predictable clearance, and hence do not require monitoring. Patients with renal insufficiency have delayed clearance and hence may have elevated levels of the drug leading to increased risk of bleeding.Keywords direct thrombin inhibitor; direct factor Xa inhibitor; stroke; heart attack; deep vein thrombosis; atrial fibrillation A long term goal in anticoagulant management has been to obtain orally active anticoagulants with predictable pharmacodynamics (thereby avoiding the need for monitoring) whose function was minimally perturbed by diet, antibiotics or common drugs frequently used by the elderly. The advent of the new orally active anticoagulants appears to have addressed many of these issues with comparable or improved safety and efficacy. Areas where these drugs show comparable or superior efficacy and/or safety to warfarin or heparin are in the prevention of deep vein thrombosis following knee or hip replacement and in the prevention of stroke associated with non valvular atrial fibrillation. Areas currently under investigation are the potential use of these agents to prevent stroke and myocardial infarction in patients with acute coronary syndromes. For purposes of this brief review, rivaroxaban (Xarelto ® ), a factor Xa inhibitor, and dabigatran (Pradaxa ® ), a thrombin inhibitor, will be discussed and compared because these two drugs have the most available clinical data (Figure 1). ¶ This work is a summary of a plenary lecture presented at the XXII International Congress on Thrombosis held in Nice, France, Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHMI Author Manuscript HHMI Author Manuscript HHMI Author ManuscriptAs the population ages, the need for anticoagulant treatment increases. For chronic treatment with orally active agents, the only available agent has been warfarin or closely related vitamin K antagonists. As the understanding of the structure and function of the coagulation enzymes increased and with the im...

show abstract

Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial

Cited by 634 publications

References 21 publications

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial

Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial

More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy—Current Data and Future Directions

What did we learn from new oral anticoagulant treatment?

Contact Info

Product

Resources

About