title: A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: The design of the GEMINI-ACS-1 phase II study.
abstract: Dual antiplatelet therapy (DAPT), the combination of aspirin and a P2Y12 inhibitor, given for 12 months remains the standard of care after presentation with acute coronary syndrome (ACS) because it has been shown to be associated with a significant reduction in ischemic events compared with aspirin monotherapy. The factor Xa inhibitor rivaroxaban was shown to be associated with a significant reduction in the composite of cardiovascular death, myocardial infarction, and stroke, and resulted in a nominal reduction in cardiovascular death, when added to background DAPT in the ATLAS ACS 2-TIMI 51 trial; however, there was excessive bleeding with this "triple-therapy" approach. The combination of rivaroxaban with P2Y12 inhibition in a "dual-pathway" approach may be an effective therapeutic regimen for the treatment of ACS, given the known importance of P2Y12 inhibition after stenting and intriguing data that the combination of an anticoagulant with clopidogrel after stenting in patients with atrial fibrillation appears an attractive option to this patient population. GEMINI-ACS-1 is a prospective, randomized, double-dummy, double-blind, active-controlled trial that will assess the safety of dual antithrombotic therapy (rivaroxaban [2.5 mg twice daily] + P2Y12 inhibitor) as compared with DAPT (aspirin [100 mg] + P2Y12 inhibitor) within 10 days of an ACS event in 3,000 patients. Patients will be randomized in a 1:1 ratio stratified by intended P2Y12 inhibitor use (clopidogrel 75 mg daily or ticagrelor 90 mg twice daily), with 1500 patients expected in each P2Y12 inhibitor strata. The primary end point is Thrombolysis in Myocardial Infarction clinically significant bleeding (major, minor, or requiring medical attention). The exploratory efficacy determination will be a composite of cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis. GEMINI-ACS-1 will assess the safety and feasibility of dual antithrombotic therapy with rivaroxaban and a P2Y12 inhibitor compared with conventional DAPT for the treatment for patients with recent ACS.
authors.affiliation: Division of Cardiology, Duke Medicine, Durham, NC; Duke Clinical Research Institute, Duke Medicine, Durham, NC. Electronic address: Thomas.povsic@duke.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.affiliation: Division of Cardiology, Duke Medicine, Durham, NC; Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.affiliation: Division of Cardiology, Duke Medicine, Durham, NC; Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Erik Magnus
authors.initials: EM
authors.lastname: Ohman
authors.affiliation: Université Paris-Diderot, Sorbonne Paris Cité, FACT, DHU-FIRE, AP-HP and INSERM U-1148, Paris, France; NHLI, Royal Brompton Hospital, Imperial College, London, UK.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Department of Medical Sciences and Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.affiliation: Janssen Research & Development, Raritan, NJ.
authors.forename: Alexei
authors.initials: A
authors.lastname: Plotnikov
authors.affiliation: Bayer HealthCare, Wuppertal, Germany.
authors.forename: Hardi
authors.initials: H
authors.lastname: Mundl
authors.affiliation: Mazankowski Alberta Heart Institute and University of Alberta, Edmonton, AB, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Welsh
authors.affiliation: University of Freiburg, Freiburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Charles Michael
authors.initials: CM
authors.lastname: Gibson
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D065427:Factor Xa Inhibitors / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D000069552:Rivaroxaban / Q000008:administration & dosage*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000069552:Rivaroxaban; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin