Critical Appraisal of the AUGUSTUS Trial

Abstract

Patient Population: Adult patients with atrial fibrillation (AF) who were indicated for use of oral anticoagulation who developed an acute coronary syndrome (ACS) event or had undergone percutaneous coronary intervention (PCI) in the last 14 days, with planned use of a P2Y 12 inhibitor for at least six months. Patients with severe renal insufficiency (defined as creatinine clearance less than 30 ml/min or serum creatinine greater than 2.5 mg/dL) and patients who were using anticoagulation for other conditions, such as prosthetic valves or venous thromboembolism, were excluded from the study. Intervention: The trial was a two-by-two factorial design comparing apixaban with a vitamin K antagonist (VKA) and comparing aspirin (ASA) with a placebo. For the first factorial comparison, a total of 2,306 patients were randomized to receive apixaban. Of these randomized patients, 2,290 patients received at least one dose of apixaban. As for the second factorial comparison, 2,307 patients were randomized to receive ASA. Of these randomized patients, 2,277 patients received at least one dose of ASA. Comparison: A total of 2,308 patients were randomized to receive VKA, and 2,259 patients received at least one dose of VKA. Those subjects had the dose adjusted to reach a target international normalized ratio (INR) within a range of 2.0 to 3.0. As for the second factorial comparison, a placebo was assigned to 2,307 patients. Of these patients, 2,279 had received at least one dose of the placebo. Outcome: The primary outcome was a composite of major and clinically relevant nonmajor bleeding defined by the International Society on Thrombosis and Hemostasis with a follow-up period of six months. A secondary outcome evaluated was a composite of all-cause death and all-cause hospitalization, as well as a composite of death or ischemic events. The primary endpoint is a composite safety outcome of ISTH major and clinically relevant non-major bleeding. ISTH major bleeding was defined as bleeding that resulted in death, occurred in a critical organ, or was associated with either a decrease in the hemoglobin level of at least 2 g per deciliter or a transfusion of at least two units of packed red cells. Anticoagulation with apixaban resulted in overall reduction in bleeding events. The reduction was similar in magnitude across the composite and individual outcomes. Using aspirin as an antiplatelet, in addition to the use of an anticoagulant, significantly increases the risk of ISTH major or clinically relevant non-major bleeding. The significance of the composite outcome was not driven by any particular outcome, since both components were shown to be statistically significant. of P2Y apixaban for six months, one nonmajor bleeding, when compared to treatment with a VKA. Aspirin led to a higher bleeding risk compared with placebo with an NNH of 14. for every 14 people with AF and recent PCI or ACS receiving a P2Y 12 inhibitor who receive treatment with aspirin for six months, nonmajor bleeding, when compared to with a placebo. The shows that of the risk the of clot