Trial data examining total events, not just first events, support choosing apixaban over warfarin and holding aspirin while continuing P2Y12 inhibitors.

Most research comparing the efficacy of different antithrombotic strategies for patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary interven­tion (PCI) examines the time to a first ischaemic or bleeding event as the primary outcome measure. However, these high-risk patients often experience multiple instances of such events, so examining the comparative efficacy of therapeutic regimens to reduce total events is worthwhile.

In a post hoc analysis of the 2­by­2 factorial, randomised, controlled, AUGUSTUS trial (NEJM JW Cardiol 17 Mar 2019 and N Engl J Med 2019; 380: 1509-­1524), the investigators assessed the incidence of total major or clinically relevant nonmajor bleeding events, total ischaemic events and total hospitalisations among 4614 patients followed for six months. All patients were receiving P2Y12 inhibitor therapy – most often clopidogrel – and were randomised to receive apixaban or warfarin and to aspirin or placebo. Results included the following:

• recurrences were common, occurring in 19% of patients experiencing a first bleeding event and in 34% of patients experiencing a first ischaemic event
• apixaban, compared with warfarin, and stopping aspirin, compared with continuing it, significantly reduced total bleeding events (28.6 vs 41.6 per 100 patient­-years, and 23.9 vs 47.1 per 100 patient­-years, respectively) without significantly increasing the ischaemic risk.

Comment: The current analysis based on multiple events affirms prior knowledge and is informative for decision making. In my practice, I stop aspirin within the first seven to 30 days after an ACS or PCI in most patients with AF (or venous thromboembolism) who receive anticoagulation. In patients for whom direct oral anticoagulants are a viable option, apixaban offers additive safety, making a combination of apixaban and a P2Y12 inhibitor (clopidogrel) the optimal regimen for most patients during the first year of treatment. After the first year, in stable patients, anticoagulation is often all we need (J Am Coll Cardiol 2025 Feb 7; epub [https://doi.org/10.1016/j.jacc.2024.12.030]).

Note to readers: Dr. Bikdeli is a coauthor of an editorial that accompanies this original article. 

Behnood Bikdeli, MD, MS, Associate Physician, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston; Instructor in Medicine, Harvard Medical School, Boston; Investigator, Yale New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, USA.

Tannu M, et al. Antithrombotic therapy to minimize total events after ACS or PCI in atrial fibrillation: insights from AUGUSTUS. J Am Coll Cardiol 2025 Feb 5; e-pub (https://doi.org/10.1016/j.jacc.2024.10.125). Bikdeli B, et al. Incorporating the totality of ischemic and hemorrhagic events: the case of the AUGUSTUS trial. J Am Coll Cardiol 2025 Feb 5; e-pub (https://doi.org/10.1016/j. jacc.2024.11.047).

This summary is taken from the following Journal Watch title: Cardiology.