FDA approves apixaban for treatment of DVT, PE

August 22, 2014

FDA has approved apixaban (Eliquis, Bristol-Myers Squibb and Pfizer) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. Combined, DVT and PE are known as VTE.

FDA has approved apixaban (Eliquis, Bristol-Myers Squibb and Pfizer) for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy. Combined, DVT and PE are known as VTE.

Apixaban now approved to reduce risk of blood clots after hip, knee surgery

It is estimated that every year, approximately 900,000 Americans are affected by DVT and PE. DVT, which may lead to PE, can be a serious medical condition, with PE requiring immediate treatment. Once a VTE has occurred, approximately 33% of patients are at risk of a recurrence within 10 years

The approval of apixaban adds to the increasing number of new oral anticoagulants, which currently include rivaroxaban and dabigatran. The newer agents have been said to reduce all-cause mortality when compared to warfarin during a follow-up, but did not have an impact on ischemic stroke or myocardial infarction, according to an online research report in The Lancet.

Apixaban includes boxed warnings for the increased risk of thrombotic events in patients who prematurely discontinue apixaban; and for the increased risk of epidural or spinal hematoma, which may cause long-term or permanent paralysis, in patients using apixaban and undergoing spinal epidural anesthesia or spinal puncture. The drug increases the risk of bleeding and can cause serious, potentially fatal, bleeding. 

The FDA approval of apixaban for the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy, is based on data from the global AMPLIFY and AMPLIFY-EXT studies.

The AMPLIFY study, a randomized, double-blind trial, was designed to demonstrate the efficacy and safety of apixaban for the treatment of DVT and PE, and included patients with confirmed symptomatic DVT or PE (2,609 for apixaban and 2,635 for standard of care,which was initial enoxaparin treatment for at least 5 days, overlapped by warfarin therapy [International Normalized Ratio (INR) range 2.0-3.0] orally for 6 months).

In the AMPLIFY study, apixaban 10 mg twice daily for 1 week followed by 5 mg twice daily for 6 months demonstrated efficacy comparable to standard of care in treating DVT and PE patients for the primary efficacy composite end point of recurrent, symptomatic VTE, or VTE-related death (2.3% vs. 2.7%, relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18; P-value<.0001 for noninferiority).

Apixaban demonstrated superiority in the primary safety end point of major bleeding versus standard of care (0.6% vs. 1.8%, relative risk 0.31; 95% CI, 0.17 to 0.55; P<.0001 for superiority). Major bleeding was defined as clinically overt bleeding that was accompanied by one or more of the following: a decrease in the hemoglobin level of 2 g/dL or more; a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least one of the following critical sites: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal; or bleeding that was fatal.

For the secondary safety end point in the AMPLIFY study, the event rates for clinically relevant nonmajor bleeding (CRNM) were fewer in apixaban-treated patients compared to standard of care-treated patients (3.9% vs. 8.0%). CRNM was defined as overt bleeding that did not meet the criteria for major bleeding but was associated with a medical intervention, contact with a physician, interruption of the study drug, or discomfort or impairment in carrying out daily activities.

In AMPLIFY, the discontinuation rate due to bleeding events was 0.7% in the apixaban-treated patients compared to 1.7% in enoxaparin/warfarin-treated patients.