Abstract 13666: New Oral Anticoagulants in Secondary Prevention of Acute Coronary Syndromes: A Meta-Analysis
Introduction: The new oral anticoagulants direct factor Xa inhibitors and direct thrombin inhibitors may be useful in preventing recurrent ischemic events after an acute coronary syndrome (ACS). We systematically reviewed the efficacy and safety of new oral anticoagulants in ACS patients.
Methods: We searchedMEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials in April 2012 for randomized controlled trials evaluating new oral anticoagulants in ACS patients. Primary outcomes included major bleeding, all-cause mortality and cardiovascular mortality; secondary outcomes were myocardial infarction (MI), stroke and severe recurrent ischemia. We used a Mantel-Haenzel random-effects model and calculated risk ratios (RRs) with 95% confidence intervals (CIs).
Results: Eight studies enrolling 34,017 participants were included. Six studies evaluated direct factor Xa inhibitors (APPRAISE, APPRAISE-2: apixaban; ATLAS ACS-TIMI 46, ATLAS ACS 2-TIMI 51: rivaroxaban; AXIOM-ACS: TAK-442; RUBY-1: darexaban) and two investigated direct thrombin inhibitors (ESTEEM: ximelagatran; RE-DEEM: dabigatran). All comparison arms used placebo and most participants were on aspirin or dual antiplatelet therapy. Overall, the new oral anticoagulants were associated with a higher risk of major bleeding (TIMI scale: RR 2.92, 95% CI 2.00-4.25, p<0.00001, I2=11%; ISTH scale: RR 2.42, 95% CI 1.78-3.29, p<0.00001, I2=0%) and a lower risk of MI (RR 0.85, 95% CI 0.74-0.98, p=0.03, I2=19%) when compared to placebo. No significant differences were observed in other outcomes. Subgroup analysis of oral direct factor Xa inhibitors revealed similar results (TIMI major bleed: RR 2.93, 95% CI 1.90-4.50, p<0.00001, I2=23%; ISTH major bleed: RR 2.51, 95% CI 1.80-3.52, p<0.00001, I2=0%; MI: RR 0.86, 95% CI 0.77-0.97, p=0.01, I2=0%); evidence on oral direct thrombin inhibitors was inconclusive due to the small number of studies.
Conclusions: New oral anticoagulants are associated with a high risk of major bleeding and a low risk of MI, with a lack of significant benefit in other clinical outcomes. Further research to establish the role of oral direct thrombin inhibitors and to evaluate the efficacy and safety of all the newer oral anticoagulants in ACS is warranted.
- © 2012 by American Heart Association, Inc.