Phase 4 Results of BMS-Pfizer Trial

The Bristol-Myers Squibb-Pfizer Alliance announced results from the Phase 4 AUGUSTUS trial evaluating Eliquis® (apixaban) versus vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) and recent acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI). Results show that in patients receiving a P2Y12 inhibitor with or without aspirin (antiplatelet therapies), the proportion of patients with major or clinically relevant non-major (CRNM) bleeding at six months was significantly lower for those treated with Eliquis compared to those treated with a VKA (10.5% vs. 14.7%, respectively; hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58-0.81; p-superiority).

AUGUSTUS, which evaluated 4,614 patients, is an open-label, prospective, randomized clinical trial designed to assess two independent hypotheses:

Whether or not Eliquis 5mg twice daily is non-inferior or superior to VKAs for the outcome of major or CRNM bleeding, as defined by the International Society on Thrombosis and Haemostasis (ISTH), in patients with NVAF and recent ACS and/or undergoing PCI with planned concomitant antiplatelet therapy (a P2Y12 inhibitor with or without low-dose aspirin).

Whether or not single antiplatelet therapy with a P2Y12 inhibitor is superior to dual antiplatelet therapy with a P2Y12 inhibitor and low-dose aspirin for the outcome of ISTH major or CRNM bleeding in patients with NVAF and recent ACS and/or undergoing PCI and planned concomitant anticoagulant therapy (either Eliquis 5mg twice daily or VKA).

Independent of the Eliquis versus VKA comparison, results also showed that in patients receiving a P2Y12 inhibitor and an anticoagulant, the proportion of patients with major or CRNM bleeding at six months was significantly higher for those receiving aspirin compared to those receiving placebo (16.1% vs. 9.0%, respectively; HR: 1.89, 95% CI: 1.59-2.24;)

Please note that Eliquis increases the risk of bleeding compared with placebo and can cause serious, potentially fatal, bleeding.

Due to concern for major bleeding, there have been ongoing questions about treating non-valvular atrial fibrillation patients with acute coronary syndrome and/or undergoing percutaneous coronary intervention. Results from this study provide additional information for physicians treating these high-risk patients, - said Renato D. Lopes, M.D., M.H.S, Ph.D.,Director, Clinical Events Classification, Duke Clinical Research Institute and Principal Investigator of AUGUSTUS.

The investigators also analyzed the pre-defined secondary composite outcomes of death or hospitalization and death or ischemic events (including myocardial infarction, stroke, definite or probable stent thrombosis or urgent revascularization). At six months, patients receiving a P2Y12 inhibitor with or without aspirin who were treated with Eliquis had lower rates of death or hospitalization (23.5% vs. 27.4%, respectively; HR: 0.83, 95% CI: 0.74-0.93; p=0.002) and similar rates of death or ischemic events (6.7% vs. 7.1%, respectively; HR: 0.93, 95% CI: 0.75-1.16; p=NS) compared to those assigned to VKA. Patients receiving a P2Y12 inhibitor and an anticoagulant who were treated with aspirin had similar rates of death or hospitalization (26.2% vs. 24.7%, respectively; HR: 1.08, 95% CI: 0.96-1.21; p=NS) and similar rates of death or ischemic events (6.5% vs. 7.3%, respectively; HR: 0.89, 95% CI: 0.71-1.11) compared to those assigned to placebo.

The AUGUSTUS trial evaluated antithrombotic regimens for the often difficult-to-treat non-valvular atrial fibrillation patient population that presents with acute coronary syndrome and/or receives percutaneous coronary intervention. These findings add to evidence from previous studies that demonstrate the safety profile of Eliquis versus a vitamin K antagonist in patients with non-valvular atrial fibrillation, -said James Rusnak, M.D., Ph.D., Chief Development Officer, Internal Medicine, Pfizer.

Atrial fibrillation is the most common arrhythmia in the world, affecting an estimated 33 million people in 2010. It is estimated that approximately 20-to-30 percent of people with atrial fibrillation also have concomitant coronary artery disease, which may result in ACS or require PCI. Additionally, five-to-ten percent of patients who undergo PCI have atrial fibrillation. While oral anticoagulants and dual antiplatelet therapy help reduce the risk of stroke and recurrent ischemic events, respectively, the combination leads to an increased risk of bleeding. Therefore, additional research has been needed to help inform antithrombotic regimens available for these high-risk patients.

Advancing care for patients at risk for stroke due to non-valvular atrial fibrillation is a key focus of the BMS-Pfizer Alliance. The AUGUSTUS trial represents our ongoing commitment to understanding anticoagulation among higher-risk patients, - said Christoph Koenen, M.D., Head of Cardiovascular Development, Bristol-Myers Squibb.

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