ATLAS ACS TIMI 51: a Phase III Study to Evaluate the Efficacy and Safety of Xarelto® in the Secondary Prevention of ACS

ATLAS ACS ACS
Acute coronary syndrome (= ACS). An umbrella term used to cover any group of clinical symptoms compatible with an acute heart attack. The subtypes of ACS 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).
2 TIMI TIMI
Thrombolysis in Myocardial Infarction (= TIMI) bleeding criteria. This is a score used to determine the likelihood of ischaemic events or mortality in patients with unstable angina or non-ST segment elevation myocardial infarction (NSTEMI). There is also a separate TIMI risk score for patients with ST segment elevation myocardial infarction (STEMI).
51: Secondary Prevention in Acute Coronary Syndrome

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 (ACS). The ATLAS study programme enrolled more than 19,000 patients.1 Based on the study results of ATLAS ACS TIMI 46, a randomized, double-blind, placebo-controlled, multicentre, dose-escalation study, rivaroxaban doses of 2.5 mg and 5 mg twice daily were selected for further evaluation in the phase III ATLAS ACS 2 TIMI 51 study based on their favourable benefit–risk profile.

Objectives

There were 2 main objectives of ATLAS ACS 2 TIMI 51:

  • To evaluate the ability of rivaroxaban to reduce the incidence of death, myocardial infarction (MI MI
    Myocardial infarction (= MI). This is commonly known as a heart attack. This is usually caused by a blood clot that stops the blood flowing to part of the heart muscle. As a result, the heart muscle becomes damaged.
    ) 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 standard antiplatelet therapy (aspirin alone or aspirin plus a thienopyridine)

Rivaroxaban was evaluated for safety and tolerability based on adverse events, clinical laboratory test, electrocardiograms, vital signs measurements and bleeding events.

Study design

The study was randomized, event-driven, placebo-controlled and double-blinded, and a total of 15,526 patients with a recent ACS event were enrolled. All patients received standard antiplatelet therapy of low-dose aspirin with or without a thienopyridine, such as clopidogrel. In addition, patients were randomized to receive one of the following regimens for at least 6 months.

  • Rivaroxaban one 2.5 mg tablet, twice daily
  • Rivaroxaban one 5 mg tablet, twice daily
  • Placebo one tablet, twice daily

Endpoints

  • The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction or stroke (ischaemic, haemorrhagic or stroke of uncertain cause)
  • The primary safety endpoint was Thrombolysis in Myocardial Infarction (TIMI) major bleeding events not associated with coronary artery bypass grafting