Abstract 13152: A Net Clinical Outcome Analysis Comparing Fatal or Irreversible Ischemic and Bleeding Events in ATLAS ACS 2 - TIMI 51
Background: Net clinical outcome analyses in ACS have mingled fatal/irreversible events with survivable/reversible events that vary greatly in their clinical impact. An efficacy & safety comparison limited to fatal/irreversible ischemic and adverse/harm events would be a way to assess the net clinical outcome.
Methods: In the ATLAS 2-TIMI 51 trial of rivaroxaban therapy among ACS patients, fatal/irreversible efficacy endpoints which included non-bleeding cardiovascular death, non-fatal MI, and ischemic stroke were analyzed separately from and compared to fatal/irreversible harm events, including fatal and intracranial hemorrhage. All endpoints were assessed in the modified intention-to-treat period.
Results: Per 10,000 patient-years of exposure, a rivaroxaban dose of 2.5 mg PO BID in patients treated with aspirin and thienopyridine was associated with 115 fewer fatal/irreversible ischemic events (663 non-bleeding cardiovascular deaths, MI or ischemic strokes for placebo vs. 548 events for 2.5 mg PO BID of rivaroxaban). In the same population, rivaroxaban was associated with 10 additional fatal/irreversible hemorrhagic events (33 fatal bleeds or intracranial hemorrhages (ICHs) for 2.5 mg PO BID of rivaroxaban vs. 23 events for placebo) per 10,000 patient-years of exposure. Taken together, there would be 105 (95% CI 6, 204) fatal/irreversible events prevented/10,000 patient-years of exposure to 2.5 mg PO BID of rivaroxaban compared with placebo. There would be 11 (115/10) fatal/ irreversible ischemic events prevented for each fatal or irreversible hemorrhagic event caused. 87 subjects (patient-years) would be needed to treat (NNT) to prevent 1 fatal/ irreversible ischemic event and 984 subjects would be needed to treat to cause 1 fatal/irreversible harm event (number needed to harm/ NNH).
Conclusion: Fatal/irreversible ischemia/hemorrhage are both clinically significant events of similar clinical impact that can be compared to assess the net clinical outcome associated with a therapy. Rivaroxaban at a dose of 2.5 mg PO BID in patients treated with aspirin and thienopyridine is associated with a net reduction in fatal/ irreversible events.
- © 2012 by American Heart Association, Inc.