AUGUSTUS Results Consistent, Regardless of Stroke History, Study Finds

Renato Lopes, MD

A post hoc analysis of data from the AUGUSTUS trial details the effects of treatment approaches with different antithrombotic regimens after acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation (AF) and a history of stroke.

Using data from 633 patients in the trial with a history of prior stroke, transient ischemic attack (TIA), or thromboembolism, investigators determined the safety and efficacy of apixaban compared with vitamin K antagonists (VKA) were consistent with the overall trial findings, irrespective of history of stroke, TIA, or thromboembolism.

“Although it is possible that aspirin might have some benefit in patients with prior stroke, in general, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status,” investigators wrote.

An open-label, prospective, multicenter, 2-by-2 factorial, randomized clinical trial, the AUGUSTUS trial enrolled 4614 patients and randomized them to either apixaban 5 mg twice-daily or VKA, or aspirin 81 mg daily, or matching placebo. In the overall trial, results demonstrated use of apixaban was associated less bleeding events and fewer hospitalizations than VKA, and aspirin was associated with increased bleeding versus placebo in patients with AF and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y12 inhibitor.

In the post hoc analysis, investigators sought to assess whether treatment effects might vary based on history of prior stroke, TIA, or thromboembolism for multiple outcomes, including major bleeding or clinically relevant nonmajor bleeding (CRNM), with major bleeding defined using International Society of Thrombosis and Haemostasias (ISTH). Secondary outcomes of interest included composite of death or hospitalization and the composite of death or ischemic events.

Of the 4581 patients with data related to history of stroke. TIA, and thromboembolism in AUGUSTUS, 633 patients had a history of stroke, TIA, or thromboembolism. Compared to those without prior stroke, TIA, or thromboembolism, these 633 patients were older, had higher CHA2DS2-VASC and HAS-BLED scores, and were more likely to have a history of prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Additionally, investigators pointed out those with a history of stroke, TIA, or thromboembolism also had a greater risk of ischemic stroke (1.60% vs 0.50%; P=.002) and were more likely to experience ISTH major or CRNM bleeding (17.1% vs 13.0%; P=.02), death or hospitalization (30.6% vs 25.2%; P=.003), and death or ischemic events (9.4% vs 6.1%; P=.001) compared to their counterparts without a history of such events.

Upon analysis, results suggested use of apixaban was associated with lower rates of ISTH major or CRNM bleeding and death or hospitalization than VKA in patients with (HR, 0.69 [95% CI, 0.46-1.03]) and without (HR, 0.68 [95% CI, 0.57-0.82]) history of stroke, TIA, or thromboembolism. Investigators pointed out those receiving aspirin had higher rates of bleeding compared to those receiving placebo, but this difference was less substantial among those with prior stroke, TIA, or thromboembolism compared to their counterparts with a history of these events. Further analysis demonstrated use of aspirin was associated with numerically lower rates of death or ischemic events compared to placebo therapy in patients (HR, 0.71 [95% CI, 0.42-1.20]) and without (HR, 0.93 [95% CI, 0.72-1.21]) prior stroke/TIA/TE, but this association was not statistically significant.

“In this subgroup analysis of the AUGUSTUS trial, patients with prior stroke/TIA/TE had a 3-fold increased risk of ischemic stroke and a higher risk of ISTH major or CRNM bleeding, death or hospitalization, and death or ischemic events than those without prior stroke/TIA/ TE. The safety and efficacy of apixaban compared with VKA was consistent with the overall trial findings, irrespective of history of stroke/TIA/TE,” wrote investigators.

This study, “Apixaban or Warfarin and Aspirin or Placebo After Acute Coronary Syndrome or Percutaneous Coronary Intervention in Patients With Atrial Fibrillation and Prior Stroke,” was published in JAMA Cardiology.