Safety and efficacy of antithrombotic therapy according to stroke and bleeding risk in patients with atrial fibrillation and acute coronary syndrome or PCI: insights from AUGUSTUS

Abstract Background The AUGUSTUS trial showed that patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) and/or PCI treated with a P2Y12 inhibitor and apixaban resulted in less bleeding and comparable ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both. We assessed the effect of apixaban versus VKA and aspirin versus placebo according to patients' baseline risk of stroke and bleeding. Methods AUGUSTUS randomized 4614 patients in a two-by-two factorial design to open label apixaban or VKA and blinded aspirin or placebo. The primary endpoint was major or clinically relevant nonmajor (CRNM) bleeding over 6 months of follow-up. The effects were assessed stratified by baseline CHA2DS2-VASc and HAS-BLED score using Cox proportional hazards models. Results 4386 patients were included for this analysis. The median age was 71 (64–77) years, 29.4% were female, 81.7% had a CHA2DS2-VASc score≥3, and 66.8% a HAS-BLED score≥3. As shown in the table, rates of bleeding were lower with apixaban (vs VKA) irrespective of baseline bleeding risk (p-value interaction: 0.23). Aspirin (vs placebo) was associated with increased bleeding irrespective of baseline risk (p-value interaction: 0.88). Apixaban use was associated with a lower risk of death or hospitalization without a significant interaction with stroke risk (p-value of interaction=0.53). No differences were found for ischemic outcomes. Conclusion An antithrombotic regimen including a P2Y12 inhibitor and apixaban is associated with less bleeding and hospitalization compared to a regimen with VKA, aspirin, or both with results consistent across CHA2DS2-VASc, and HAS-BLED scores. Our findings support the use of apixaban and a P2Y12 inhibitor without aspirin during the first 6 months for most patients with AF and ACS and/or PCI, regardless of stroke and bleeding risk. Risk category Apixaban (event) VKA (event) Hazard ratio (95% CI) Interaction p-value Major or CRNM bleeding (HASBLED) ≤2 8.8% 14.4% 0.57 (0.41–0.78) 0.23 ≥3 12.1% 16.3% 0.72 (0.59–0.88) Death or hospitalization (CHA2DS2-VASc) ≤2 19.7% 21.5% 0.92 (0.67–1.25) 0.53 ≥3 25.0% 29.2% 0.82 (0.73–0.94) Aspirin (event) Placebo (event) Major or CRNM bleeding (HASBLED) ≤2 15.1% 8.4% 1.86 (1.36–2.56) 0.88 ≥3 17.8% 10.4% 1.81 (1.47–2.23) Death or hospitalization (CHA2DS2-VASc) ≤2 21.7% 19.5% 1.09 (0.80–1.49) 0.90 ≥3 27.8% 26.4% 1.07 (0.94–1.21) Funding Acknowledgement Type of funding source: Private grant(s)