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When patients with atrial fibrillation develop acute coronary syndrome (ACS) or require percutaneous coronary intervention (PCI), they theoretically become candidates for triple antithrombotic therapy — an anticoagulant for atrial fibrillation, plus dual antiplatelet therapy for the coronary event. However, such regimens are associated with high rates of bleeding. In this industry-sponsored international study, researchers examined the efficacy and safety of two-drug alternatives in 4600 patients with atrial fibrillation who had either ACS (with or without PCI) or elective PCI.
All patients received a P2Y12 inhibitor (nearly always clopidogrel) and additionally were randomized twice — to apixaban or a vitamin K antagonist (VKA) and to aspirin or no aspirin. This randomization resulted in four treatment groups:
Aspirin, clopidogrel, apixaban [Eliquis]
Aspirin, clopidogrel, VKA
Clopidogrel, apixaban
Clopidogrel, VKA
At 6 months, major or clinically relevant nonmajor bleeding occurred more commonly with triple therapy than with two-drug therapy (16% vs. 9%) and more commonly with VKA-containing regimens than with apixaban-containing regimens (15% vs. 11%). Rates of myocardial infarction, stroke, and death were similar in the two-drug and three-drug groups. Hence, the best overall outcome (less bleeding, without sacrificing protection against ischemic events or death) was with the two-drug regimen of clopidogrel plus apixaban.
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
These results make a strong case for avoiding three antithrombotic agents in anticoagulated patients with atrial fibrillation who develop coronary events that are typically treated with dual antiplatelet therapy. The combination of clopidogrel plus apixaban — omitting aspirin — offered the most favorable balance of benefit and harm in this trial. However, an editorialist argues that the study might have been underpowered to show some protection against ischemic events with aspirin, and he argues that selected high-risk patients might still benefit from at least a few weeks of triple therapy.