Table 3. New Oral Anticoagulants—Data in Acute Coronary Syndrome (ACS)
Dabigatran (Pradaxa)Rivaroxaban (Xarelto)*Apixaban (Eliquis)
Clinical trialRE-DEEM (phase II)28ATLAS-ACS-2-TIMI-51 (phase III) 29APPRAISE-2 (phase III)32
Patient population1861 patients presenting with STEMI or NSTEMI7817 patients presenting with STEMI7392 patients with recent ACS and ≥2 additional risk factors for recurrent ischemic events
Primary outcomeComposite of major or clinically relevant minor bleedingComposite of CV death, MI, or strokeEfficacy: a composite of CV death, MI, or stroke
Safety: major TIMI bleeding
ResultsThere was a dose-dependent increase in bleeding with dabigatran compared with placebo: HR, 1.77 (95% CI, 0.70–4.50) for 50 mg; HR, 2.17 (95% CI, 0.88–5.31) for 75 mg; HR, 3.92 (95% CI, 1.72–8.95) for 110 mg; and HR, 4.27 (95% CI, 1.86–9.81) for 150 mg (all given twice daily)Rivaroxaban reduced the primary efficacy endpoint of CV death, MI, or stroke compared with placebo (8.4 vs 10.6%; HR, 0.81; 95% CI, 0.67–0.97; P = .019)There was no significant reduction in the occurrence of ischemic events when comparing apixaban to placebo (7.5 vs 7.9%; HR, 0.95; 95% CI, 0.80–1.11; P = .51)
Rivaroxaban increased non-CABG TIMI major bleeding (2.2 vs 0.6%; P = .001) and ICH (0.6 vs 0.1%; P = .015) without a significant increase in fatal bleeding (0.2 vs 0.1%, P = .51)Apixaban demonstrated an increase in major TIMI bleeding compared with placebo (1.3 vs 0.5%; HR, 2.59; 95% CI, 1.50–4.46; P = .001)
ConclusionsDabigatran was associated with a dose-dependent increase in bleeding events in this patient population when compared to placeboRivaroxaban reduced CV events in this patient population when compared with placebo, albeit at an increased risk of bleedingApixaban increased the frequency of major bleeds without a significant reduction in ischemic events compared with placebo
  • * The FDA has denied the proposed expanded indication for rivaroxaban as a treatment for patients with ACS to reduce the risk of MI, stroke, death, or stent thrombosis.30 Rivaroxaban 2.5 mg twice daily is approved in Europe for secondary prevention of ACS in combination with standard antiplatelet therapy.31

  • APPRAISE-2, Apixaban for Prevention of Acute Ischemic Events 2; ATLAS-ACS-2-TIMI-51, Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome—Thrombolysis In Myocardial Infarction-51; CABG, coronary artery bypass grafting; CV, cardiovascular; HR, hazard ratio; ICH, intracranial hemorrhage; MI, myocardial infarction; RE-DEEM, The Randomized Dabigatran Etexilate Dose Finding Study in Patient with Acute Coronary Syndromes Post Index Event with Additional Risk Factors for Cardiovascular Complications Also Receiving Aspirin and Clopidogrel. STEMI, ST-elevated myocardial infarction; NSTEMI, non-ST elevated myocardial infarction; TIMI, thrombosis in myocardial infarction; CI, confidence interval.