Apixaban in AF patients with recent ACS/PCI: Drop aspirin after 30 days

Patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) who receive a P2Y₁₂ inhibitor are better off with apixaban than a vitamin K antagonist (VKA) as the use of aspirin for up to 30 days results in an equal trade-off between an increase in severe bleeding and reduction in severe ischaemic events [1].

The AUGUSTUS trial was a large, prospective, randomised trial with a two-by-two factorial design that showed that AF patients with recent ACS or PCI who used a P2Y₁₂ inhibitor and apixaban had significantly less bleeding compared with warfarin (10.5% vs 14.7%, respectively; P<0.0001) [2]. No significant difference was seen between patients who received additional aspirin versus placebo in the secondary outcomes of composites death or hospitalisation and ischaemic events: death or ischaemic event for apixaban versus VKA (6.7% vs 7.1%; P>0.05); death or hospitalisation for aspirin versus placebo (26.2% vs 24.7%; P>0.05); death or ischaemic event for aspirin versus placebo (6.5% vs 7.3%; P>0.05); ICH for apixaban versus VKA (0.2% vs 0.6%; P>0.05); ICH for aspirin versus placebo (0.4% vs 0.4%; P>0.05).

The objective of this post-hoc secondary analysis, presented by Prof. John Alexander (Duke University, USA) was to explore the balance of risk (i.e. bleeding) and benefit (i.e. ischaemic events) between randomisation and 30 days, and between 30 days and 6 months, with aspirin and placebo, in a cohort of 4,614 patients enrolled in AUGUSTUS. Although the choice of P2Y₁₂ inhibitor was left to the treating physician, more than 90% of the patients were treated with clopidogrel, which is consistent with most guidance statements.

From randomisation to 30 days, the risk of severe bleeding was 2.1% with aspirin versus 1.1% with placebo (absolute risk difference 0.97%; 95% CI 0.23-1.70). Severe ischaemic events occurred in 1.7% patients on aspirin versus 2.6% on placebo (absolute risk difference -0.91; 95% CI -1.74 to -0.08). From 30 days to 6 months, the risk of severe bleeding with aspirin was 3.7% versus 2.5% with placebo (risk ratio 1.25; 95% CI 0.23- 2.27) while the risk of severe ischaemic event was 3.8% versus 4.0%, respectively (absolute risk difference -0.17; 95% CI -1.33 to 0.98).

Prof. Alexander pointed out some limitations of the study, such as patients receiving aspirin prior to randomisation (median 6 days) in both arms, which could have influenced subsequent bleeding or ischaemic outcomes. Also, severe, intermediate, and broad composite bleeding and ischaemic event outcomes may not be of completely comparable severity, and the number of events was small, especially regarding the more severe outcomes.

In conclusion, apixaban with or without aspirin seems to balance the bleeding risk with possible ischaemic benefit in the first 30 days of treatment; continued aspirin is associated with more bleeding.

1. 
   
   1. Alexander JH, et al. Abstract 409-08. ACC/WCC 28-30 March 2020.
   2. Lopes RD, et al. N Engl J Med. 2019;380:1509-1524.

 



Posted on 8 September, 202029 February, 2024