Secondary Prevention in Acute Coronary Syndrome: ATLAS
ATLAS is the abbreviation for Anti-Xa Therapy to Lower cardiovascular events in addition to Aspirin with/without thienopyridine therapy in Subjects with Acute Coronary Syndrome. It is an umbrella term for the clinical study programme of rivaroxaban in the secondary prevention of Acute Coronary Syndrome. The ATLAS study programme is planned to enroll up to 19,500 patients.66
Objectives
There are 2 main objectives of ATLAS:
- To evaluate the ability of rivaroxaban to reduce the incidence of death, myocardial infarction (MI) or stroke in patients with recent ACS treated with Aspirin alone or Aspirin plus a thienopyridine
- To evaluate the safety of rivaroxaban in patients with recent ACS who are treated with Aspirin alone or Aspirin plus a thienopyridine
Rivaroxaban will be evaluated for safety and tolerability based on adverse events, clinical laboratory test, ECGs, vital signs measurements, and bleeding events.
ATLAS ACS TIMI 51: a phase lIl study to evaluate the efficacy and safety of rivaroxaban in the secondary prevention of ACS
The ATLAS ACS TIMI 51 study is a global, phase III clinical study designed to evaluate the safety and efficacy of rivaroxaban in addition to standard therapy.
Study design
The study is randomized, event-driven, placebo-controlled and double-blinded. It is planned to enroll up to 16,000 patients. All patients will receive standard antiplatelet therapy of low-dose aspirin with or without a thienopyridine, such as clopidogrel. Patients will then be randomized to additionally receive one of the following regimens for at least six month.
- Rivaroxaban one 2.5 mg tablet, twice daily
- Rivaroxaban one 5 mg tablet, twice daily
- Placebo one tablet, twice daily
The primary efficacy endpoint of ATLAS ACS TIMI 51 is the composition of cardiovascular death, MI or stroke.66 The safety is assessed by the incidence of major bleeding events that are not associated with coronary artery bypass graft (CABG) surgery.
ATLAS ACS TIMI 46: a phase ll dose-escalation study of rivaroxaban
ATLAS ACS TIMI 46 is a phase II study of secondary prevention of acute coronary syndrome (ACS) to establish the safety and efficacy of rivaroxaban in patients with recent ACS.20
Study design
ATLAS ACS TIMI 46 was a randomised, double-blind, placebo-controlled, multicentre, dose-escalation study conducted in about 3,500 post-ACS patients to evaluate rivaroxaban in combination with Aspirin (stratum I) or Aspirin plus thienopyridine (stratum II) against antiplatelet therapy alone. Total daily doses of rivaroxaban included 5, 10, 15, or 20 mg. The patients were assigned by the treating physician to the respective strata before they were randomly assigned to one of the following regimens:
- Rivaroxaban one tablet once daily plus Aspirin alone or plus Aspirin and a thienopyridine
- Rivaroxaban one tablet twice daily plus Aspirin alone or plus Aspirin and a thienopyridine
- Placebo plus Aspirin alone or plus Aspirin and a thienopyridine
All groups received treatment for 6 months. The patients had a follow-up visit 1 month after the last study dose was given.20
The two doses selected for further evaluation in the pivotal Phase III programme – 2.5 mg and 5 mg dosed twice daily – showed the best balance between efficacy and safety.66
- 66 - A Randomized, Double-Blind, Placebo-Controlled, Event-Driven Multicenter Study to Evaluate the Efficacy and Safety of Rivaroxaban in Subjects With a Recent Acute Coronary Syndrome. Available at http://clinicaltrials.gov/ct2/show/NCT00809965. Accessed 2 November 2010
- 20 - A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Escalation and Dose-Confirmation Study to Evaluate the Safety and Efficacy of Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a Thienopyridine in Subjects With Acute Coronary Syndromes. Available at http://clinicaltrials.gov/ct2/show/NCT00402597. Accessed 2 November 2010.
- Acute coronary syndrome
- An umbrella term used to cover any group of clinical symptoms compatible with an acute heart attack. The subtypes of acute coronary syndrome include unstable angina (in which the heart muscle is not damaged), and two forms of heart attack in which the heart muscle is damaged. These latter types are named according to the appearance of the electrocardiogram as non-ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI).
- Efficacy
- The ability of a drug to produce the desired effect.
