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Published on: February 28, 2012
Antithrombotic Therapy in Patients With Atrial Fibrillation After Acute Coronary Syndromes or Percutaneous
Ralf E Harskamp1, Alexander C Fanaroff2, Renato D Lopes3
1Amsterdam UMC-Location Academic Medical Center, Amsterdam, the Netherlands.
Insights
Apixaban use with a P2Y12 inhibitor, instead of vitamin K antagonists (VKA) and aspirin, reduces bleeding events in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention. This strategy maintains comparable ischemic event rates across various bleeding and stroke risk levels.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) or with acute coronary syndrome (ACS) often require dual antithrombotic therapy.
- Balancing the risk of ischemic events against bleeding complications is crucial in these high-risk patients.
- Vitamin K antagonists (VKAs) and aspirin have been standard, but associated with significant bleeding risks.
Purpose of the Study:
- To evaluate the safety and efficacy of apixaban compared to VKAs, and aspirin versus placebo in patients with AF and ACS and/or PCI.
- To assess antithrombotic regimen effectiveness based on established bleeding (HAS-BLED) and stroke (CHA2DS2-VASc) risk scores.
Main Methods:
- The AUGUSTUS trial randomized 4,614 patients in a 2x2 factorial design to apixaban or VKA, and aspirin or placebo.
- The primary endpoint was major or clinically relevant nonmajor bleeding over a 6-month follow-up period.
- Cox proportional hazards models analyzed treatment effects stratified by HAS-BLED (≤2 vs. ≥3) and CHA2DS2-VASc (≤2 vs. ≥3) scores.
Main Results:
- Apixaban significantly reduced bleeding compared to VKA, irrespective of baseline bleeding risk (HAS-BLED scores).
- Aspirin use increased bleeding rates significantly, regardless of baseline bleeding risk.
- Apixaban demonstrated a trend towards lower death or hospitalization risk compared to VKA, particularly in patients with higher stroke risk (CHA2DS2-VASc ≥3).
Conclusions:
- The findings support using apixaban with a P2Y12 inhibitor, omitting aspirin, for patients with AF and ACS and/or PCI.
- This regimen is recommended irrespective of individual patient bleeding or stroke risk profiles.
- The study provides evidence for optimizing antithrombotic therapy in complex cardiovascular patient populations.
Background:
The use of apixaban instead of vitamin K antagonists (VKA) as well as dropping aspirin results in less bleeding and comparable ischemic events in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention treated with a P2Y12 inhibitor.
Objectives:
The authors assessed the safety and efficacy of antithrombotic regimens according to HAS-BLED and CHA2DS2-VASc scores in AUGUSTUS (The Open-Label, 2 × 2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention).
Methods:
In AUGUSTUS, 4,614 patients were randomized in a 2-by-2 factorial design to open-label apixaban or VKA and blinded aspirin or placebo. The primary endpoint was major or clinically relevant nonmajor bleeding over 6 months of follow-up. Cox proportional hazards models were used to assess treatment effects by baseline HAS-BLED (≤2 vs ≥3) and CHA2DS2-VASc (≤2 vs ≥3) scores.
Results:
Of 4,386 (95.1%) patients with calculable scores, 66.8% had HAS-BLED ≥3 and 81.7% had CHA2DS2-VASc ≥3. Bleeding rates were lower with apixaban than VKA irrespective of baseline risk (HR: 0.57; 95% CI: 0.41-0.78 [HAS-BLED ≤2]; HR: 0.72; 95% CI: 0.59-0.88 [HAS-BLED ≥3]; interaction P = 0.23). Aspirin increased bleeding irrespective of baseline risk (HR: 1.86; 95% CI: 1.36-2.56 [HAS-BLED ≤2]; HR: 1.81; 95% CI: 1.47-2.23 [HAS-BLED ≥3]; interaction P = 0.88). Apixaban resulted in a lower risk of death or hospitalization than VKA without a significant interaction with baseline stroke risk (HR: 0.92; 95% CI: 0.67-1.25 [CHA2DS2-VASc ≤2]; HR: 0.82; 95% CI: 0.73-0.94 [CHA2DS2-VASc ≥3]; interaction P = 0.53).
Conclusions:
Our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for most patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention, irrespective of a patient's baseline bleeding and stroke risk (NCT02415400).
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