Equal benefit and harm from 30 days of aspirin in patients with atrial fibrillation and a recent coronary event
In patients with atrial fibrillation (AF) and a recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI), adding apixaban to a P2Y12 inhibitor resulted in a lower rate of bleeding compared with a vitamin K antagonist (warfarin) with a reduced risk of death or rehospitalization. In both arms, the addition of aspirin resulted in an excess of bleeding without any difference in efficacy, according to a secondary analysis of the AUGUSTUS trial.
The objective of this post hoc analysis of AUGUSTUS was to explore the balance of risk (bleeding) and benefit (ischemic events) between randomization and 30 days and 6 months with aspirin and placebo.
The use of aspirin acutely and for up to 30 days resulted in an equal increase in severe bleeding, said lead investigator John Alexander, MD, from the Duke Clinical Research Institute, Durham, NC. From randomization to 30 days, the rates of major bleeding were 2.11% with aspirin and 1.14% with placebo, for an absolute difference of 0.97 (95% confidence interval [CI] 0.23–1.70).
The rates of severe ischemic events—a composite of cardiovascular (CV) death, myocardial infarction (MI), stent thrombosis, or stroke—from randomization to 30 days were also similar, 1.66% in the aspirin arm and 2.57% in the placebo arm (absolute difference -0.91%, 95% CI -1.74 to -0.08).
After 30 days, aspirin continued to increase bleeding without significantly reducing ischemic events. From 30 days to 6 months, rates of major bleeding were 3.71% with aspirin and 2.45% with placebo, an absolute difference of 1.25% (95% CI, 0.23–2.27), and the rates of CV death, MI, stent thrombosis, or stroke were 3.82% with aspirin and 3.99% with placebo, an absolute difference of -0.17% (95% CI, -1.33 to 0.98).
“Using aspirin up to 30 days might be reasonable, and these results should inform patient-centric shared decision-making regarding the ideal duration of aspirin after an ACS or PCI in patients with AF receiving oral anticoagulation,” said Dr. Alexander.
In AUGUSTUS, 4,614 patients with AF who had an indication for oral anticoagulation and an ACS or PCI or both with planned P2Y12 inhibitor use for at least 6 months were randomized to open-label apixaban, 5 mg twice daily, or a vitamin K antagonist with a target internationalized ratio of 2 to 3. Patients were also randomized to blinded aspirin, 81 mg/day, or matching placebo. All patients received a P2Y12 inhibitor. Most patients received aspirin acutely prior to randomization, which occurred a median of 6 days after ACS or PCI.
The mean patient age was 70.7; 29% were female, and 36% had diabetes. Mean CHA2DS2-VASc score was 4.0. Some 61% of patients enrolled had ACS as a qualifying event.
The overall AUGUSTUS results, published in 2019, demonstrated significantly less bleeding with placebo vs aspirin and no significant difference in the rate of the composite of death or hospitalization or the rate of ischemic events between patients assigned to aspirin and those assigned to placebo, although there was numerically more of some ischemic events (stent thrombosis, MI, and urgent revascularization) in patients assigned to placebo. Analysis of stent thrombosis events suggested that most of the increased risk with placebo was present within 30 days of randomization, prompting the current analysis.
As a limitation, patients received aspirin before randomization in both arms, which may have influenced subsequent bleeding or ischemic outcomes, said Dr. Alexander.
A manuscript of the results was accepted for publication in Circulation (in press).
Julia Indik, MD, PhD, from the University of Arizona Health Sciences, Tucson, who was not involved in the trial, calculated a number needed to treat with 30 days of aspirin to prevent one severe ischemic event to be about 100, which is approximately the same as the number needed to harm (severe bleeding event). She commented, therefore, that perhaps a duration of aspirin shorter than 30 days may improve the risk-benefit ratio, although further research is needed.
“I can’t identify a shorter time period that would be reasonable, recognizing that what we did was post hoc,” responded Dr. Alexander.
The AUGUSTUS trial was funded by the Bristol-Myers Squibb/Pfizer Alliance. John H. Alexander, MD, FACC, Duke University Med Center Disclosures: Consultant Fees/Honoraria: AbbVie, Inc., Bayer, Bristol Myers Squibb, CryoLife, Inositec, Pfizer Inc, Portola, Quantum Genomics Research/Research Grants Boehringer Ingelheim, Bristol Myers Squibb, CryoLife , CSL Behring, GlaxoSmithKline. Julia H. Indik, MD, PhD, FACC, University of Arizona Medical Center Disclosures: Nothing to disclose.