Bristol-Myers Squibb Company, a global biopharmaceutical company, and Pfizer Inc., one of the world's premier innovative biopharmaceutical companies, announced that the first patient has been enrolled into the phase 4 clinical trial, AUGUSTUS. This two-by-two factorial, randomized controlled trial will evaluate the safety of Eliquis versus warfarin or other vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation (NVAF) and a recent acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), also known as a stent.
In addition, patients will also be randomized to aspirin or placebo. All patients will receive a P2Y12 inhibitor (such as clopidogrel) in combination with either Eliquis or a VKA. Eliquis is approved to reduce the risk of stroke and systemic embolism in patients with NVAF.
“Limited data are available to inform the use of Eliquis and other oral anticoagulants in NVAF patients who require concomitant dual antiplatelet therapy,” said Renato D. Lopes, M.D., MHS, Ph.D., Duke Clinical Research Institute (DCRI) director of clinical events classification and principle investigator for AUGUSTUS.
“With the first patient now enrolled in AUGUSTUS, we will be collecting data that will help inform the safety profile of Eliquis for NVAF patients who have suffered a recent ACS and/or are undergoing PCI.”
“This trial is critical as patients with NVAF frequently have concomitant coronary artery disease, which may result in an ACS event or require PCI that requires antiplatelet therapy,” said John H. Alexander, M.D., MHS, FACC, director of cardiovascular research at the DCRI and chair of the AUGUSTUS executive committee.
AUGUSTUS is anticipated to enroll 4,600 eligible patients from 30 countries. The two-by-two factorial design permits for the testing of two hypotheses in the study population. First, it will evaluate whether or not Eliquis is noninferior to a VKA on the combined outcome of major bleeding and clinically relevant non-major (CRNM) bleeding when studied in an open-label manner. Second, in a double-blind manner, it will evaluate whether or not the addition of aspirin to an anticoagulant and P2Y12 inhibitor results in significantly more major and CRNM bleeding in the study population.
Secondary objectives include the comparison of Eliquis to VKA (with concomitant P2Y12 therapy) for superiority on major or CRNM bleeding; death, stroke, myocardial infarction, stent thrombosis, urgent revascularization, or re-hospitalisation for any cause; and the comparison of a P2Y12 inhibitor plus aspirin versus a P2Y12 inhibitor alone with either Eliquis or VKA with respect to death, stroke, myocardial infarction, stent thrombosis, or urgent revascularization and re-hospitalization for any cause.
The study population will include men and women age 18 and older with NVAF with the planned or existing use of an oral anticoagulant for reducing the risk of thromboembolism. In addition, participants must have had an ACS or PCI with a stent within the prior 14 days, as well as planned use of an approved P2Y12 inhibitor for at least six months.
AUGUSTUS is one of several new clinical trials that will help provide additional information on the safe and appropriate use of Eliquis for certain specific types of patients within currently approved indications.
Atrial fibrillation (AF) is the most common type of heartbeat disorder, or irregular heartbeat. Nonvalvular atrial fibrillation (NVAF) refers to cases in which the AF occurs in the absence of rheumatic mitral valve disease, a prosthetic heart valve, or mitral valve repair. It was estimated that in 2014, 6.4 million people in the US and in 2010, over six million individuals in Europe, had AF. The lifetime risk of AF is estimated to be approximately 25 per cent for individuals 40 years of age or older. One of the most serious medical concerns for individuals with AF is the increased risk of stroke, which is five times higher in people with AF than those without AF. Additionally, AF-related strokes tend to be more severe than other strokes with an associated 30-day mortality rate of 24 per cent and a 50 per cent likelihood of death within one year.
Acute coronary syndrome (ACS) is a term used to describe situations in which the blood supplied to the heart muscle is suddenly blocked, and includes myocardial infarction (MI), also known as a heart attack, and unstable angina (sudden, severe chest pain that typically occurs when a person is at rest). ACS affects an estimated 1.4 million people in the US and an estimated 1.38 million people in Europe. ACS is a subcategory of coronary artery disease (CAD), the most common type of cardiovascular disease. Cardiovascular diseases are the number-one cause of death worldwide. According to the World Health Organisation, CAD alone resulted in 7.4 million deaths during 2012.
Percutaneous coronary intervention (PCI), also known as coronary angioplasty, is a procedure used to open blocked or narrowed coronary arteries. Angioplasty also is used as an emergency procedure during a heart attack. According to the Centers for Disease Control and Prevention, there are approximately 500,000 PCIs performed annually in the US alone.
Eliquis is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, Eliquis decreases thrombin generation and blood clot formation. Eliquis is approved for multiple indications in the US based on efficacy and safety data from seven phase 3 clinical trials. Eliquis is a prescription medicine indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF); for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE; and to reduce the risk of recurrent DVT and PE, following initial therapy.
Eliquis is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Eliquis is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery. Eliquis is indicated for the treatment of DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy.
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialise apixaban, an oral anticoagulant discovered by Bristol-Myers Squibb. This global alliance combines Bristol-Myers Squibb's long-standing strengths in cardiovascular drug development and commercialisation with Pfizer’s global scale and expertise in this field.