Review of thromboembolism treatments finds one laggard, two contenders

Unfractionated heparin-vitamin K antagonist combination was found to be the least effective of venous thromboembolism treatments in a meta-analysis published online Sept. 17 in JAMA while some novel oral anticoagulants carried lower bleeding risks.

This meta-analysis of 44 studies explored eight anticoagulation options for treating patients with acute venous thromboembolism. The research team compared unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux (Arixtra, GlaxoSmithKline) in combination with vitamin K antagonists; LMWH with dabigatran (Pradaxa, Boehringer Ingelheim) or edoxaban (Lixiana, Daiichi Sankyo); rivaroxaban (Xarelto, Bayer/Janssen Pharmaceutica); apixaban (Eliquis, Pfizer/Bristol-Meyers Squibb) or LMWH alone.

Lana A. Castellucci, MD, of the Ottawa Hospital Research Institute at the University of Ottawa, and colleagues wanted to determine the relative efficacy and safety of the options available. Recurrent thromboembolism, major bleeding and death were among the outcomes measured.

The found that largely there were no significant differences between the treatments for safety and efficacy when compared with LMWH combined with vitamin K antagonist therapy. However, there were some differences of note.

Rivaroxaban and apixaban offered the lowest bleeding risks (hazard ratios 0.55 and 0.31, respectively) when compared against LMWH and vitamin K antagonist therapy. Castellucci et al wrote that apixaban had the “greatest probability of being the least harmful therapy among all treatment regimens assessed.”

On the other hand, they found that UFH with vitamin K antagonist was the least effective strategy. With LMWH and vitamin K antagonist combination as the reference, UFH and vitamin K antagonist therapy had a hazard ratio of 1.42, showing an increased risk of recurrent venous thromboembolism.

Over three months of treatment, 1.84 percent of patients given UFH and vitamin K antagonist combination experienced recurrent venous thromboembolism, as opposed to 1.3 percent of LMWH and vitamin K antagonist combination patients.

Castellucci et al wrote that their findings were consistent with guideline recommendations, suggesting the use of LMWH or fondaparinux over UFH for initial treatment of pulmonary embolism or acute thrombosis. However, based on the findings of this meta-analysis, the research team advised physicians to consider new oral anticoagulants, particularly apixaban or rivaroxaban, when applicable due to the lower risk of bleeding.