Apixaban plus a P2Y12 inhibitor best balances bleeding and ischemic events in patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention
Clinical question: Can the HAS-BLED and CHA2DS2-VASc scores be used to identify subgroups of patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) who would benefit from an antithrombotic regimen other than apixaban plus a P2Y12 inhibitor?
Dr. Klein
Background: The combination of AF and coronary artery disease poses a clinical dilemma in choosing the optimal antithrombotic regimen. The AUGUSTUS trial, which is the basis for this post-hoc analysis, included patients with AF hospitalized for ACS and/or PCI with the planned use of a P2Y12 inhibitor for at least six months. Within 14 days of the index event, patients underwent randomization to receive apixaban versus vitamin K antagonist (VKA) and to receive aspirin versus placebo. All patients received a P2Y12 inhibitor (mostly clopidogrel). The antithrombotic regimen of apixaban plus a P2Y12 inhibitor resulted in less bleeding and fewer hospitalizations, without significant differences in ischemic events when compared to regimens that included a VKA, aspirin, or both.
Setting: Multiple medical centers in 33 different countries included in the AUGUSTUS trial
Study design: Post-hoc analysis of the AUGUSTUS trial (open-label, two-by-two factorial, randomized, controlled trial)
Synopsis: This study stratified the AUGUSTUS patient population by baseline risks for bleeding and stroke using the HAS-BLED and CHA2DS2-VASc scores, respectively. A total of 4,368 patients were included in the analysis. No significant interactions were found on treatment effects of apixaban versus VKA or aspirin versus placebo across HAS-BLED and CHA2DS2-VASc scores. The data suggest an antithrombotic regimen of apixaban and a P2Y12 inhibitor without aspirin is preferable across a wide range of bleeding and stroke risk in patients with AF in the first six months following ACS and/or PCI.
Notably, many guidelines recommend a short period of dual-antiplatelet therapy (often seven days) after PCI or ACS, and these findings may not apply to patients very shortly after the index event. In addition, this post-hoc analysis may be limited by the fact that the AUGUSTUS trial was not powered to detect interactions between outcomes according to these subgroups. Therefore, small but meaningful differential treatment effects in subgroups may have been obscured.
Bottom line: In patients with AF and recent ACS or PCI, the antithrombotic regimen of apixaban plus a P2Y12 inhibitor appears best to balance bleeding risk and efficacy, irrespective of baseline HAS-BLED and CHA2DS2-VASc scores.
Citation: Harskamp RE, et al. Antithrombotic therapy in patients with atrial fibrillation after acute coronary syndromes or percutaneous intervention. J Am Coll Cardiol. 2022;79(5):417-27. doi:10.1016/j.jacc.2021.11.035.
Dr. Klein is an assistant professor at Tufts University School of Medicine, Boston, and a hospital medicine physician at Maine Medical Center, Portland, Maine.
