Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome
Topic: Anticoagulation in acute coronary syndrome (Factor Xa inhibitors)
- Apixaban, an oral direct factor Xa inhibitor, may reduce recurrent ischemia when added to antiplatelet therapy after an acute coronary syndrome.
- Randomized, international, double-blind, multicenter, clinical trial
- Apixaban (5 mg twice daily, or 2.5 mg twice daily if CrCl < 40 mL/min). Other standard care was left to the discretion of the treating physician.
- Placebo. Other standard care was left to the discretion of the treating physician.
- 7,392 patients
- Patients with recent (within 7 days) STEMI or non-STEMI ACS, and treated with aspirin or aspirin plus P2Y12-receptor inhibitor. Also, 1 additional risk factor for recurrent ischemic events was required (age greater than 65, DM, prior MI, prior stroke, PAD, CHF, EF < 40%, mild to moderate renal insufficiency).
- Aspirin allergy, planned angiography, PCI, CABG, or other intervention, persistent severe HTN, severe renal insufficiency, active bleeding or high risk for bleeding, coagulopathy, prior stroke within 3 months, NYHA 4 heart failure, thrombocytopenia, anemia, indication for long term anticoagulation, chronic NSAID use.
- 241 days
- Composite of cardiovascular death, myocardial infarction, or ischemic stroke.
Primary safety endpoint:
- Major bleeding, according to the Thrombolysis in Myocardial Infarction (TIMI) definition.
- Composite of cardiovascular death, myocardial infarction, ischemic stroke, or unstable angina; the composite of cardiovascular death, myocardial infarction, ischemic or hemorrhagic stroke, or fatal bleeding; and the composite of death from any cause, myocardial infarction, or ischemic or hemorrhagic stroke.
- Median age 67 years, 32% female.
- Index event was STEMI in 40%, NSTEMI in 42%, and UA in 18%.
- 52% underwent angiography, 44% had PCI, and 55% were treated medically.
- 97% were on aspirin, 81% were receiving aspirin plus P2Y12 inhibitor (predominantly clopidogrel).
- Primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 patients (7.5%) assigned to apixaban and in 293 patients (7.9%) assigned to placebo (HR with apixaban, 0.95; CI 0.80-1.11; P=0.51).
- There were also no significant differences between the apixaban and placebo groups with respect to any of the secondary efficacy outcomes.
- TIMI major bleeding occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban, compared with 18 of the 3642 patients (0.5%) who received at least one dose of placebo (HR with apixaban, 2.59; CI, 1.50-4.46; P=0.001).
- There were more events of fatal bleeding (5 vs. 0), intracranial bleeding (12 vs. 3).
- The trial was terminated prematurely because of an increase in major bleeding events with apixaban.
TAKE AWAY: No benefit of abixaban in addition to standard antiplatelet therapy in high risk patient with STEMI/NSTEMI ACS, and was associated with significantly increased number of major bleeding events.