Objective: To provide a comprehensive review of the pharmacology, pharmacokinetics, pharmacodynamics, clinical trial data, adverse effects, and drug interactions of apixaban.
Data sources: An English-language literature search was performed with MEDLINE/PubMed from January 2007 to August 2011 using the search terms apixaban, factor Xa inhibitors, FXa inhibitors, BMS-562247-01, venous thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, ACS, atrial fibrillation, atrial arrhythmias, total hip replacement or arthroplasty, total knee replacement or arthroplasty, and orthopedic surgery to identify relevant articles. The references of the retrieved articles, professional society meeting abstracts, and the Web site www.clinicaltrials.gov were reviewed to identify other pertinent articles.
Study selection and data abstraction: Pertinent original studies involving apixaban's pharmacology, pharmacokinetics, drug interactions, and clinical efficacy and safety data were included.
Data synthesis: Results of 2 large Phase 3 trials suggest that apixaban is superior for stroke and systemic embolism prevention compared to both aspirin and warfarin in patients with atrial fibrillation (AF); rates of major bleeding and intracranial hemorrhage were similar to those of aspirin but significantly reduced compared to warfarin. Completed trials in orthopedic surgery found apixaban to be superior to enoxaparin in total hip replacement (THR) surgery but inferior in total knee replacement (TKR) surgery, with similar rates of major bleeding. A Phase 3 trial of apixaban in acute coronary syndrome was stopped early because of excess bleeding. Future Phase 3 trials will help to determine apixaban's role for treatment of deep vein thrombosis and pulmonary embolism. Currently, apixaban is approved only in Europe for prophylaxis of venous thromboembolism in adults who have undergone elective THR or TKR.
Conclusions: A Phase 3 trial in patients with AF revealed apixaban to be superior to warfarin for stroke and systemic embolism prophylaxis, with lower rates of major bleeding. Further studies will help to confirm the role of apixaban for other indications.