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The optimal combination of antiplatelet and anticoagulant regimens for patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or those requiring percutaneous coronary intervention (PCI) is unknown. In AUGUSTUS, an industry-sponsored, multinational trial, investigators randomized 4614 patients (median age, 71; 29% women; median CHAD2DS2-VASc score, 4; median HAS-BLED score, 3) with AF and an ACS or PCI ≤14 days and needing a P2Y12 inhibitor for ≥6 months to one of the following:
Standard-dose apixaban plus low-dose aspirin
Apixaban plus placebo
A vitamin K antagonist (VKA) plus aspirin
VKA plus placebo
The P2Y12 inhibitor in most patients (93%) was clopidogrel. The median time in therapeutic range with a VKA was 59%.
By 6 months, significantly fewer apixaban patients than VKA patients experienced the primary endpoint (major or clinically relevant nonmajor bleeding; 10.5% vs. 14.7%) or were hospitalized. Those receiving aspirin were more likely to experience the primary endpoint than placebo recipients (16.1% vs. 9.0%), but these two groups did not differ on secondary composite endpoints (death or hospitalization; death or ischemic events). Patients randomized to a VKA plus aspirin experienced the greatest incidence of death or hospitalizations.
Lopes RD et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med 2019 Mar 17; [e-pub]. (https://doi.org/10.1056/NEJMoa1817083)
Mehta SR.Refining antithrombotic therapy for atrial fibrillation and acute coronary syndromes or PCI. N Engl J Med 2019 Mar 17; [e-pub]. (https://doi.org/10.1056/NEJMe1902214)
Comment
This trial addresses a common clinical scenario in patients with AF, and its clever design allowed testing of the independent effects of standard-dose apixaban and low-dose aspirin added to a P2Y12 inhibitor. Recent studies have also found that serious bleeding is minimized in AF patients needing a PCI by using a direct oral anticoagulant instead of a VKA (NEJM JW Cardiol Oct 2017 and N Engl J Med 2017; 377:1513; NEJM JW Cardiol Dec 2016 and N Engl J Med 2016; 375:2423). The AUGUSTUS trial extends these findings by suggesting that omitting low-dose aspirin further decreases bleeding without increasing adverse effects, at least in the short term. However, a few limitations warrant caution in generalizing the findings to our patients. Patients likely received aspirin before randomization. The apixaban to VKA comparison was open-labeled, and patients receiving VKA were in therapeutic range only 59% of the time. As almost all patients received clopidogrel, these results may not be generalizable to other P2Y12 inhibitors. Finally, the trial was not adequately powered to detect small differences in ischemic events, which are likely to increase with early discontinuation of aspirin.