Apixaban outperforms warfarin regardless of prior stroke, TIA, or TE

Apixaban outperformed warfarin in preventing ischaemic events regardless of prior stroke, transient ischaemic attack (TIA), or thromboembolic event (TE) in patients with atrial fibrillation (AF) with recent acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI),  a prespecified secondary analysis of the AUGUSTUS trial has shown.

Bleeding was lower with the apixaban-containing regimen than with warfarin, so was the rate of death or rehospitalization. In both arms, the addition of aspirin resulted in greater bleeding with no difference in efficacy. [ISC 2020, abstract LB22]

“A strategy of apixaban plus a P2Y12 inhibitor without aspirin has the most favourable outcomes, and triple therapy — a vitamin K antagonist [VKA] plus aspirin plus a P2Y12 inhibitor — should be avoided,” said lead investigator Dr Maria Cecilia Bahit, chief of cardiology at INECO Neurociencias in Rosario, Santa Fe, Argentina. “These results are reassuring to physicians … even in a high-risk group with prior stroke, ‘less is more’.”

Results support AUGUSTUS

The new analysis supports the main findings of the AUGUSTUS trial which demonstrated less bleeding and fewer deaths and hospitalizations with an antithrombotic regimen that included apixaban without aspirin vs treatment with a VKA (warfarin) plus aspirin in patients with AF, with either ACS or PCI and receiving a P2Y12 inhibitor (clopidogrel in over 90 percent of patients). [N Engl J Med 2019; 380:1509-1524]

AUGUSTUS included 4,614 patients. The sub-analysis divided the AUGUSTUS population into two groups: patients with prior stroke, TIA, or TE and those without. Of the 4,581 patients with information available about prior stroke, 13.8 percent had prior stroke, TIA, or TE. They were also older, with higher CHA₂DS₂-VASc and HAS-BLED* scores, and were more likely to have prior bleeding, heart failure, diabetes, and previous use of oral anticoagulant.

“In both groups, apixaban was safer than warfarin, causing less major bleeding and resulting in less death or hospitalization regardless of prior stroke, TIA, or TE,” Bahit reported at ISC 2020. “Patients without prior stroke, TIA, or TE receiving aspirin had higher bleeding rates than those not on aspirin, whereas the difference between aspirin and placebo appeared to be less substantial in those with prior stroke, TIA, or TE.”

Commenting on the study, Dr Mitchell S.V. Elkind, president-elect, American Heart Association and professor of neurology and epidemiology at Columbia University New York, New York City, New York, US said: “The AUGUSTUS trial was a study that looked at a complicated group of patients. These patients often require anticoagulation for AF and antiplatelet agents for coronary intervention, heart attack, and perhaps, displaced coronary artery. And so, the question has always been: How many blood thinners should these patients be on? Potentially, they could be on three different agents [an anticoagulant and two antiplatelet drugs], and we know that all of those drugs together pretty dramatically increase the risk of bleeding.”

Can we do without aspirin?

The results seen in the AUGUSTUS trial held true for those with a history of cerebrovascular disease in the secondary analysis. “Apixaban was more effective than warfarin, with a lower risk of bleeding in those with  a history of cerebrovascular disease, just as it was in those without,” Elkind added.

“Overall, the results confirmed that the use of apixaban appeared safer and these patients need not be on aspirin as well as other antiplatelet regimen. Patients with a history of stroke had a lower risk of bleeding  …  and so, one could argue that they should be on an agent like apixaban, as well as an alternate antiplatelet agent, like clopidogrel, for example, without the addition of aspirin.”