Dr. Erika Kancler
Background Non-vitamin K oral anticoagulants have become an appealing alternative treatment for the prevention of stroke in non-valvular atrial fibrillation and in treatment of venous thromboembolism. The major limitation to the use of these drugs is the lack of reversal agents. The purpose of this review is to investigate the development and efficacy of novel agents for reversal of NOACs. Methods Two separate literature searches were conducted in the PubMed database using the terms “prothrombin complex concentrate” and “idarucizumab”, respectively. Only in vivo clinical trials involving human subjects within the last five years were included for possible analysis. Studies with disease-specific populations (i.e. non-valvular atrial fibrillation, etc.) were excluded. Three studies were chosen based on these inclusion and exclusion criteria. Results A phase I trial investigating Cofact, a non-activated, four factor prothrombin complex concentrate (PCC), demonstrated that Cofact normalized the prothrombin time (PT) and endogenous thrombin potential (ETP) in all participants anticoagulated with rivaroxaban but had no effect on the prolongation of the activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT) in participants anticoagulated with dabigatran etexilate. In another phase I trial clinical trial, idarucizumab, at doses of 4 and 5 + 2.5 g, effectively reversed anticoagulation with dabigatran etexilate immediately and at 24 hours, as assessed by the dilute thrombin time (dTT), ECT, thrombin time (TT), and aPTT. An ongoing phase III clinical trial with 5 g idarucizumab also demonstrated effective reversal of dabigatran etexilate in roughly 86 percent of patients at 24 hours. Conclusion Only idarucizumab has been approved by the FDA for clinical use. Therefore, dabigatran etexilate is preferable to the factor Xa inhibitors for oral anticoagulation in adult patients, based on the current availability of an approved, effective reversal agent.
Elliott S, Hoskins J. Platelet rich plasma vs. corticosteroid injections in treatment of tendinopathies. JMU Scholarly Commons Physician Assistant Capstones. http://commons.lib.jmu.edu/pacapstones/2/. Published August 1, 2016.