Apixaban Bests Warfarin For Stroke Patients with AFib in AUGUSTUS Analysis

Maria Cecilia Bahit, MD

A secondary analysis of the AUGUSTUS trial indicates apixaban, which demonstrated associations with decreased bleeding, death, and hospitalization compared to warfarin, is safe and effective as a blood-thinning agent in stroke patients.

Presented at American Stroke Association’s International Stroke Conference (ISC) 2020 in Los Angeles, CA, the secondary analysis confirms the results seen in previously presented AUGUSTUS that suggested apixaban use resulted in less bleeding and fewer events than patients treated with a vitamin K antagonist.

“These results reinforce the main results of the AUGUSTUS trial by assuring physicians that even in a high-risk group of patients with prior stroke ’less is more’,” said lead investigator Maria Cecilia Bahit, MD, chief of cardiology at INECO Neurociencias in Rosario, Santa Fe, Argentina, in a statement. “In other words, a strategy of apixaban plus a P2Y12 inhibitor without aspirin has the most favorable outcomes, and triple therapy—a vitamin K antagonist plus aspirin plus a P2Y12 inhibitor—should be avoided.”

The AUGUSTUS trial was a global, multicenter study that included 4614 patients with AFib and an acute coronary syndrome or those undergoing PCI with planned treatment with a P2Y12 inhibitor were randomly assigned to receive 5 mg apixaban twice daily or a vitamin k antagonist and to receive aspirin or matching placebo for 6 months.

Presented at ACC 19, the trial found patients receiving apixaban had a 31% reduction in bleeding risk (P< .001) while having a bleeding risk of 7.3%, which was lower than that seen with vitamin K antagonist and aspirin. Overall, the primary endpoint of major or clinically relevant nonmajor bleeding occurred in 10.5% of patients receiving apixaban compared to 14.7% of patients receiving a vitamin K antagonist (P< .001).

The current analysis from ISC 20 examined the efficacy and safety outcomes with apixaban or vitamin K antagonist and aspirin or placebo according to prior stroke, TIA, or thromboembolism. Of the 4614 patients, 4581 had prior stroke information available and 13.8% had experienced a prior stroke, TIA, or thromboembolism.

Differences in baseline characteristics were noted among patients with a prior stroke, TIA, or thromboembolism. Differences included those with prior stroke, TIA, thromboembolism were older, had higher CHA₂DS₂-VAS_C and HAS-BLED scores, and were more likely to have prior bleeding, heart failure, diabetes, and previous use of oral anticoagulant.

When compared with vitamin K antagonists use, apixaban was associated with lower rates of International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant nonmajor bleeding and death or hospitalization—regardless of history of prior stroke, TIA, or thromboembolism. In patients without prior stroke, TIA, or thromboembolism, aspirin was associated with higher rates of bleeding than those not receiving aspirin, but the differences observed between aspirin and placebo were not as substantial among patients with prior stroke, TIA, or thromboembolism (P-interaction = .011).

Overall, the results of the current analysis were consistent with the overall trial findings regardless of history of prior stroke, TIA, or thromboembolism. Furthermore, aspirin was associated with an increase in ISTH major or clinically relevant major bleeding—especially in patients without a history or stroke, TIA, thromboembolism.

This study, “Apixaban or Warfarin and Aspirin or Placebo After Acute Coronary Syndrome or PCI in Patients With Atrial Fibrillation and Prior Stroke: Insights From the AUGUSTUS Trial,” was presented at ISC 20.