Venous thromboembolism (deep vein thrombosis, DVT, and pulmonary embolism, PE) affects on average 300,000 to 600,000 people each year and is the third most common cause of vascular-related death in the United States.1,2 Current standard of practice is to treat with anticoagulation for at least 3 months, however therapy may be extended depending on patient circumstances.3,4 Choosing when to extend anticoagulant therapy in patients with VTE can be difficult. The risk versus benefit profile must be weighed with practical limitations to include monitoring, cost, administration, and adherence. Newer anticoagulants such as apixaban may offer some advantages over the conventional anticoagulants in that they do not require therapeutic monitoring, are orally administered, and have a better risk vs. benefit profile. Apixaban is a direct thrombin inhibitor, approved for the prevention of systemic embolism in patients with non-valvular atrial fibrillation.6 The use of apixaban in extended prophylaxis of VTE was recently evaluated in the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-line Therapy-Extended Treatment (AMPLIFY-EXT) trial.7
In this trial, Agnelli and colleagues looked that the efficacy and safety of apixaban 2.5 mg and 5 mg twice daily for the extended treatment (for 12 months) of VTE in patients whose risk for recurrent events due to cessation of anticoagulation therapy equaled the risk for bleeding with continuation of therapy. Patients completed at least 6-12 months of standard anticoagulation therapy or completed treatment as part of the AMPLIFY trial (apixaban versus enoxaparin/warfarin) for a DVT and/or PE. Individuals were excluded if they required on-going anticoagulation, dual antiplatelet therapy or aspirin 165 mg or higher daily. The primary efficacy outcome was a composite of recurrent symptomatic VTE (fatal or nonfatal PE plus DVT) and death from any cause. Safety endpoints included major bleeding (primary) and clinically relevant non-major bleeding (secondary); definitions were consistent with pervious anticoagulant studies.7
A total of 2486 patients were enrolled with two-thirds with an initial diagnosis of DVT and about 90% with an unprovoked VTE. Both apixaban 2.5 mg and 5 mg twice-daily were superior to placebo for the prevention of recurrent VTE and all-cause mortality (RR 0.33, 95% CI 0.22-0.48 and RR 0.36, 95% CI 0.25-0.53, p<0.001, respectively). Primary efficacy outcomes were reported in 3.8%, 4.2% and 11.6% of patients, respectively. As expected, the number of recurrent symptomatic VTEs 30-days post study discontinuation was higher in both apixaban treatment groups. Major bleeding was reported in 4 patients who received placebo, 2 patients who received apixaban 2.5 mg and 1 patient who received apixaban 5mg; resulting in no statistically significant difference between treatment groups. Likewise, secondary safety outcomes rates were found to be similar among treatment groups. No difference in primary or secondary efficacy and safety outcomes rates was seen upon comparison of the two apixaban treatment groups. Authors concluded that both dosing regimens were safe, efficacious and simple to use for the prevention of recurrent VTE in patients with equipoise risk.7
While apixaban is not currently approved in the United States for treatment of VTE, the AMPLIFY-EXT is promising in that apixaban was effective at preventing recurrent VTE with extended treatment without an added risk of bleeding. Authors calculated the number of patients who would need to treated (NNT) to prevent one recurrent nonfatal or fatal VTE was 14; while the calculated number needed to harm (NNH) was 200. While the results were positive, it should be noted that only 15% of this patient population was over the age of 75 and only a select number of patients were reported to have moderate or severe renal impairment or weigh less than 60 kilograms. The presence of one or more of these baseline characteristics ...