|Systematic (IUPAC) name|
|Excretion||75% biliary, 25% renally|
|Molecular mass||459.497 g/mol|
|(what is this?)|
Apixaban (BMS-562247-01, tradename Eliquis) is an anticoagulant for the treatment of venous thromboembolic events. It is a direct factor Xa inhibitor. Apixaban has been available in Europe since May 2012. In the United States, it is undergoing phase III trials for the prevention of venous thromboembolism. An FDA decision on apixaban which was expected on June 28, 2012 was delayed. On August 21, 2014, Pfizer announced that Apixaban was now FDA approved for treatment and secondary prophylaxis of DVT and PE. It is being developed in a joint venture by Pfizer and Bristol-Myers Squibb.
Apixaban is indicated for the following:
- To lower the risk of stroke and embolism in patients with nonvalvular atrial fibrillation.
- Deep vein thrombosis (DVT) prophylaxis. DVT's may lead to pulmonary embolism (PE) in knee or hip replacement surgery patients.
- Treatment of both deep vein thrombosis (DVT) and pulmonary embolism (PE).
- To reduce the risk of recurring DVT and PE after initial therapy.
Apixaban is recommended by the National Institute for Health and Clinical Excellence for the prevention of stroke and systemic embolism in people with non-valvular atrial fibrillation and at least one of the following risk factors: prior stroke or transient ischemic attack, age 75 years or older, diabetes, or symptomatic heart failure. This recommendation was based on the results of a single 18,201 person Phase 3 trial comparing people treated with apixaban to people treated with warfarin and having an international normalized ratio ((NR) target range of 2.0 to 3.0. In this trial, apixaban was associated with a reduced risk of stroke and systemic embolism compared to warfarin over a period of 1.8 years (hazard ratio 0.79). The risk of fatal or disabling stroke was also reduced in the apixaban treatment arm (hazard ratio 0.71). Apixaban was associated with fewer total deaths than warfarin, though the difference was only marginally statistically significant (HR 0.89, p=0.047).The average person in the warfarin arm of the trial remained within the targeted INR range was 62%, which the institute concluded was typical of people on warfarin therapy in the United Kingdom.
Premature discontinuation of any oral anticoagulant, including apixaban, increases thrombotic event risk for reasons other than pathological bleeding or completion of therapy course. To reduce this risk, administering another anticoagulant is advised.
Apixaban can increase the risk of bleeding and may even cause serious, potentially fatal, bleeding. Concurrent use with drugs affecting hemostasis (e.g. other anticoagulants, heparin, aspirin and other antiplatelet drugs, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs) can further increase the risk of bleeding.
When spinal/epidural anesthesia or puncture is utilized, patients who are being treated with anti-thrombotic agents for the prevention of thromboembolic complications are at risk for developing a hematoma, which can cause long-term or permanent paralysis. The risk of this may be increased by using epidural or intrathecal catheters after a surgical operation or from the concurrent use of medicinal agents that affect hemostasis.
Mechanism of action
Apixaban is a highly selective, orally bioavailable, and reversible direct inhibitor of free and clot-bound factor Xa. Factor Xa catalyzes the conversion of prothrombin to thrombin, the final enzyme in the coagulation cascade that is responsible for fibrin clot formation. Apixaban has no direct effect on platelet aggregation, but by inhibiting factor Xa, it indirectly decreases platelet formation induced by thrombin.
A 2007 trial showed that apixaban was equivalent to enoxaparin/open-label heparin in preventing thrombosis in patients who had undergone a knee replacement. A 2010 trial showed that apixaban was superior to enoxaparin in preventing thrombosis in patients undergoing elective hip replacement surgery, with similar bleeding rates.
A 2011 trial showed that in patients with atrial fibrillation who have failed or are not candidates for vitamin K antagonist therapy, apixaban, as compared with aspirin, reduced the risk of stroke or systemic embolism in patients experiencing atrial fibrillation by more than 50% (from 3.7% per year with aspirin to 1.6% per year with Apixaban). Difference in death rates did not reach statistical significance. A 2011 trial showed that patients receiving apixaban after acute coronary syndrome experienced an increased rate of major bleeding episodes without a significant reduction in recurrent ischemic events. For this reason, the trial was terminated early. In a head-to-head study (Phase 3 ARISTOTLE trial) of apixaban versus warfarin, apixaban met both its primary endpoint (“noninferiority” to warfarin in preventing strokes) and a key secondary endpoint (superior compared to warfarin in avoiding major bleeding).
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