Rivaroxaban in acute coronary syndromes – is it prime time?

Abstract

Arterial thrombosis in acute coronary syndrome (ACS) is associated with activation of platelets and the coagulation cascade. Persistent thrombin levels have been reported after ACS in such patients. Novel oral anticoagulants without a need of close monitoring and frequent blood tests such as warfarin can provide a chronic beneficial effect on recurrent ischaemic events in such a population. Rivaroxaban, a new oral factor Xa inhibitor, has been tried for this indication in the ‘Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51’ (ATLAS ACS 2-TIMI 51) trial using a low dose regimen in an attempt to balance the adverse effects of bleeding related to chronic anticoagulation on background of dual antiplatelet therapy for ACS, and the beneficial effects on recurrent coronary ischemia. The role of rivaroxaban in this context has been discussed in detail in this review.

Keywords::

• acute coronary syndrome
• anticoagulants
• ischemic heart disease
• rivaroxaban
• Xa inhibitors

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Excess thrombin formation persists for at least 26 weeks beyond the acute phase once the coagulation system is activated in the acute coronary syndrome (ACS).

• Chronic anticoagulation may provide further benefit to reduce recurrent ischemic events in ACS population in addition to potent platelet inhibition.

• Rivaroxaban (Xarelto, Bayer Schering Pharma AG, Berlin, Germany) is a highly selective, reversible direct oral factor Xa inhibitor and exerts a dose-dependent inhibition of factor Xa in humans.

• Anti-Xa Therapy to Lower CV events In Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis in Myocardial Infarction 51 (ATLAS ACS 2-TIMI 51) trial results suggest rivaroxaban reduce the composite primary end point of cardiovascular death, MI and stroke, at the cost of increased major bleeding and intracranial hemorrhage but not the risk of fatal bleeding.

• The mortality curves in ATLAS ACS 2-TIMI 51 support chronic therapy with low dose of 2.5 mg b.i.d. post-ACS in patients treated with aspirin and clopidogrel.

• The US FDA has raised serious concerns about the validity of ATLAS ACS 2-TIMI 51 trial data, which include missing follow-up data, differential event rates in the patients who dropped out and inaccurate reporting of mortality, with more errors in the treatment arm.

• High proportion of undetermined vital statuses in the original reported data render the claimed mortality rates unreliable.

• Existing data from trials on novel anticoagulants including ATLAS ACS 2-TIMI 51 due to the discussed limitations do not support adding chronic anticoagulation to the standard treatment of ACS at this stage.