AUGUSTUS is the largest trial in this high-risk patient population requiring both anticoagulant and antiplatelet therapies
PRINCETON, NJ & NEW YORK, NY, USA I March 17, 2019 I The Bristol-Myers Squibb–Pfizer Alliance today 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<0.001). These data are featured as a late-breaking oral presentation at the American College of Cardiology’s (ACC) 68th Annual Scientific Session 2019 in New Orleans, LA (Abstract 405-08) and simultaneously published in the New England Journal of Medicine.
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).
*2.5mg twice daily if patients met two or more of the following dose-reduction criteria: age ≥ 80 years, weight ≤ 60 kg or creatinine ≥ 1.5mg/dL (133 micromol/L).
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; p<0.001).
Please note that Eliquis increases the risk of bleeding compared with placebo and can cause serious, potentially fatal, bleeding. Please see below for Important Safety Information, including information from the APPRAISE-2 clinical trial that was terminated early due to higher rates of bleeding for apixaban compared to placebo in post-ACS patients without an indication for oral anticoagulant.1
“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,” said Renato D. Lopes, M.D., M.H.S, Ph.D., Director, Clinical Events Classification, Duke Clinical Research Institute and Principal Investigator of AUGUSTUS. “Results from this study provide additional information for physicians treating these high-risk patients.”
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,” said James Rusnak, M.D., Ph.D., Chief Development Officer, Internal Medicine, Pfizer. “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.”
Atrial fibrillation is the most common arrhythmia in the world, affecting an estimated 33 million people in 2010.2 It is estimated that approximately 20-to-30 percent of people with atrial fibrillation also have concomitant coronary artery disease,3,4 which may result in ACS or require PCI. Additionally, five-to-ten percent of patients who undergo PCI have atrial fibrillation.5,6,7,8 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,” said Christoph Koenen, M.D., Head of Cardiovascular Development, Bristol-Myers Squibb. “The AUGUSTUS trial represents our ongoing commitment to understanding anticoagulation among higher-risk patients.”
About AUGUSTUS
AUGUSTUS is an international, multicenter, open-label, randomized controlled trial with a two-by-two factorial design to compare Eliquis (apixaban) with vitamin K antagonists (VKAs) and aspirin with placebo in 4,614 patients with non-valvular atrial fibrillation (NVAF) and recent acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI), and are receiving a P2Y12 inhibitor for at least six months. The treatment regimen comparing Eliquis with VKA was open-label; however, the regimen comparing aspirin with aspirin placebo was double blind. Patients were evaluated for eligibility during their ACS and/or PCI hospitalization. 37.3 percent of patients included in the study had ACS undergoing PCI, 23.9 percent of patients had medically-managed ACS and 38.8 percent of patients underwent elective PCI. The primary outcome is the composite of major or clinically relevant non-major (CRNM) bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH).9 A key secondary outcome is the composite of death or first hospitalization. Other secondary outcomes include the composite of death or ischemic events (myocardial infarction, stroke, definite or probable stent thrombosis or urgent revascularization). AUGUSTUS was designed to be a safety study and did not include a primary efficacy endpoint.
About Atrial Fibrillation
Atrial fibrillation (AF) is the most common type of arrhythmia, 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 U.S. and in 2010, over six million individuals in Europe, had AF. The lifetime risk of AF is estimated to be approximately 25 percent 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 percent and a 50 percent likelihood of death within one year.
About Acute Coronary Syndrome
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 U.S. 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 Organization, CAD alone resulted in 7.4 million deaths during 2012.
About Percutaneous Coronary Intervention
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 U.S. alone.
About Eliquis
Eliquis (apixaban) 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 U.S. based on efficacy and safety data from multiple 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.
About the Bristol-Myers Squibb/Pfizer Collaboration
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize 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 commercialization with Pfizer’s global scale and expertise in this field.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
About Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @PfizerNews, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
i Alexander JH et al. Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome. New England Journal of Medicine. 2011;365:699-708
ii Peterson ED, Pokorney SD. New Treatment Options Fail to Close the Anticoagulation Gap in Atrial Fibrillation. Journal of the American College of Cardiology. 2017;69(20)
iii The AFFIRM Investigators. Baseline characteristics of patients with atrial fibrillation: the AFFIRM study. American Heart Journal. 2002; 143: 991-1001
iv Capodanno, D., Angiolillo, DJ. Management of antiplatelet and anticoagulant therapy in patients with atrial fibrillation in the setting of acute coronary syndromes or percutaneous coronary interventions. Circulation: Cardiovascular Interventions. 2014;7:133-124
v Rubboli A, Colletta, M, Herzfeld J, et al. Periprocedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention. Coronary Artery Disease. 2007;18:193-199
vi Wang TY, Robinson LA, Ou FS et al. Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: physician practice in the CRUSADE registry. American Heart Journal. 2008;155:361-8
vii Perez-Gomez F, Alegria E, Berjon J, et al. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Journal of the American College of Cardiology. 2004;44:1557-66
viii Lip GY, Huber K, Andreotti, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Thrombosis and Haemostasis. 2010;103:13-28
ix Kaatz S., Ahmad D., Spyropoulos AC, et al. Definition of clinically relevant non‐major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non‐surgical patients: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2015;13(11):2119-26
SOURCE: Pfizer
Post Views: 20
AUGUSTUS is the largest trial in this high-risk patient population requiring both anticoagulant and antiplatelet therapies
PRINCETON, NJ & NEW YORK, NY, USA I March 17, 2019 I The Bristol-Myers Squibb–Pfizer Alliance today 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<0.001). These data are featured as a late-breaking oral presentation at the American College of Cardiology’s (ACC) 68th Annual Scientific Session 2019 in New Orleans, LA (Abstract 405-08) and simultaneously published in the New England Journal of Medicine.
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).
*2.5mg twice daily if patients met two or more of the following dose-reduction criteria: age ≥ 80 years, weight ≤ 60 kg or creatinine ≥ 1.5mg/dL (133 micromol/L).
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; p<0.001).
Please note that Eliquis increases the risk of bleeding compared with placebo and can cause serious, potentially fatal, bleeding. Please see below for Important Safety Information, including information from the APPRAISE-2 clinical trial that was terminated early due to higher rates of bleeding for apixaban compared to placebo in post-ACS patients without an indication for oral anticoagulant.1
“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,” said Renato D. Lopes, M.D., M.H.S, Ph.D., Director, Clinical Events Classification, Duke Clinical Research Institute and Principal Investigator of AUGUSTUS. “Results from this study provide additional information for physicians treating these high-risk patients.”
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,” said James Rusnak, M.D., Ph.D., Chief Development Officer, Internal Medicine, Pfizer. “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.”
Atrial fibrillation is the most common arrhythmia in the world, affecting an estimated 33 million people in 2010.2 It is estimated that approximately 20-to-30 percent of people with atrial fibrillation also have concomitant coronary artery disease,3,4 which may result in ACS or require PCI. Additionally, five-to-ten percent of patients who undergo PCI have atrial fibrillation.5,6,7,8 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,” said Christoph Koenen, M.D., Head of Cardiovascular Development, Bristol-Myers Squibb. “The AUGUSTUS trial represents our ongoing commitment to understanding anticoagulation among higher-risk patients.”
About AUGUSTUS
AUGUSTUS is an international, multicenter, open-label, randomized controlled trial with a two-by-two factorial design to compare Eliquis (apixaban) with vitamin K antagonists (VKAs) and aspirin with placebo in 4,614 patients with non-valvular atrial fibrillation (NVAF) and recent acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI), and are receiving a P2Y12 inhibitor for at least six months. The treatment regimen comparing Eliquis with VKA was open-label; however, the regimen comparing aspirin with aspirin placebo was double blind. Patients were evaluated for eligibility during their ACS and/or PCI hospitalization. 37.3 percent of patients included in the study had ACS undergoing PCI, 23.9 percent of patients had medically-managed ACS and 38.8 percent of patients underwent elective PCI. The primary outcome is the composite of major or clinically relevant non-major (CRNM) bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH).9 A key secondary outcome is the composite of death or first hospitalization. Other secondary outcomes include the composite of death or ischemic events (myocardial infarction, stroke, definite or probable stent thrombosis or urgent revascularization). AUGUSTUS was designed to be a safety study and did not include a primary efficacy endpoint.
About Atrial Fibrillation
Atrial fibrillation (AF) is the most common type of arrhythmia, 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 U.S. and in 2010, over six million individuals in Europe, had AF. The lifetime risk of AF is estimated to be approximately 25 percent 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 percent and a 50 percent likelihood of death within one year.
About Acute Coronary Syndrome
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 U.S. 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 Organization, CAD alone resulted in 7.4 million deaths during 2012.
About Percutaneous Coronary Intervention
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 U.S. alone.
About Eliquis
Eliquis (apixaban) 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 U.S. based on efficacy and safety data from multiple 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.
About the Bristol-Myers Squibb/Pfizer Collaboration
In 2007, Pfizer and Bristol-Myers Squibb entered into a worldwide collaboration to develop and commercialize 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 commercialization with Pfizer’s global scale and expertise in this field.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
About Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @PfizerNews, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
i Alexander JH et al. Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome. New England Journal of Medicine. 2011;365:699-708
ii Peterson ED, Pokorney SD. New Treatment Options Fail to Close the Anticoagulation Gap in Atrial Fibrillation. Journal of the American College of Cardiology. 2017;69(20)
iii The AFFIRM Investigators. Baseline characteristics of patients with atrial fibrillation: the AFFIRM study. American Heart Journal. 2002; 143: 991-1001
iv Capodanno, D., Angiolillo, DJ. Management of antiplatelet and anticoagulant therapy in patients with atrial fibrillation in the setting of acute coronary syndromes or percutaneous coronary interventions. Circulation: Cardiovascular Interventions. 2014;7:133-124
v Rubboli A, Colletta, M, Herzfeld J, et al. Periprocedural and medium-term antithrombotic strategies in patients with an indication for long-term anticoagulation undergoing coronary angiography and intervention. Coronary Artery Disease. 2007;18:193-199
vi Wang TY, Robinson LA, Ou FS et al. Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: physician practice in the CRUSADE registry. American Heart Journal. 2008;155:361-8
vii Perez-Gomez F, Alegria E, Berjon J, et al. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. Journal of the American College of Cardiology. 2004;44:1557-66
viii Lip GY, Huber K, Andreotti, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/stenting. Thrombosis and Haemostasis. 2010;103:13-28
ix Kaatz S., Ahmad D., Spyropoulos AC, et al. Definition of clinically relevant non‐major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non‐surgical patients: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2015;13(11):2119-26
SOURCE: Pfizer
Post Views: 20
