Management of Venous Thromboembolism

Abstract

Objective: To review clinical data on direct oral anticoagulants (DOACs) used in the acute treatment of venous thromboembolism (VTE) as well as practical considerations when using these products. Data Sources: Searches of PubMed and Google Scholar for VTE, deep vein thrombosis, pulmonary embolism, and relevant drug international nonproprietary names were conducted. Additional online searches were conducted for prescribing information. Study Selection and Data Extraction: Relevant articles on dabigatran, rivaroxaban, apixaban, and edoxaban for the management of VTE compared with oral vitamin K antagonists (VKAs; published between 1966 and December 2015) were reviewed and summarized, together with information on dosing, pharmacokinetics/pharmacodynamics, and drug-drug interactions. Data Synthesis: The DOACs have the potential to circumvent many of the disadvantages of VKAs. At a minimum, they greatly increase the available therapeutic options, thus providing a greater opportunity for clinicians to select a management option that best fits the needs of individual patients. Despite the significant advance that DOACs represent, they are not without risk and require careful consideration of a number of clinical issues to optimize safety and efficacy. Conclusions: The emergence of DOACs for the management of thromboembolic disorders represents a paradigm shift from oral VKAs. The DOACs provide similar efficacy and improved safety in selected patients as compared with VKAs. Clinicians treating VTE need to be familiar with the intricacies involved in using these agents, including the appropriate dose selection for the relevant indication, avoidance of drug-drug and drug-disease interactions, and consideration of dose adjustments in specific clinical situations, such as organ dysfunction.

Periprocedural Management of Direct Oral Anticoagulants Surrounding Cardioversion and Invasive Electrophysiological Procedures

“…After oral administration, all DOACs achieve peak concentrations within 1–3 hours, providing quick, predictable, and concentration-dependent anticoagulation. 57 This is advantageous particularly at the time of therapy initiation, as bridging with UFH or low molecular–weight heparin can be avoided. Key considerations for withholding periprocedural DOACs include the dosing interval, primary route of elimination, concomitant use of antiplatelet agents or other drugs influencing plasma concentrations, and baseline bleeding risk of the surgical/procedural intervention.…”

“…With half-lives of 7–14 hours, DOACs typically reach subtherapeutic concentrations 24–48 hours after the last dose, allowing patients to be unprotected for shorter periods than with warfarin. 57 Dabigatran, which is most dependent on renal function (80% renal clearance) may need to be withheld for longer periods, depending on baseline creatinine clearance and bleeding risk associated with the upcoming procedure. Like other drugs that are metabolized at least in part by the liver, the DOACs should not be coadministered with P-glycoprotein inducers like rifampin (which reduces exposure to DOACS 58 , 59 ) and prescribed with caution or avoided in patients with renal insufficiency who are comedicated with P-glycoprotein inhibitors (dabigatran 58 ).…”

Anticoagulant therapies for acute venous thromboembolism among a cohort of patients discharged from Canadian urban and rural hospitals

“… 5–10 Moreover, the DOACs (rivaroxaban, dabigatran, apixaban and edoxaban) offer advantages over the traditional therapy of an injectable anticoagulant (typically low-molecular-weight heparin (LMWH)) overlapped with warfarin. 11 Unlike warfarin therapy, all DOACs have standardised dosing regimens that lack the need for routine coagulation monitoring and offer a therapeutic effect within hours of administration. Rivaroxaban and apixaban do not require initial therapy with an injectable anticoagulant, further streamlining care delivery.…”

Safety and timing of resuming dabigatran after major gastrointestinal bleeding reversed by idarucizumab

“…The recent development of direct oral anticoagulants (DOACs), including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism (VTE) and in atrial fibrillation (AF) has been associated with greater clinical benefit compared with oral vitamin K antagonists (VKA). 1 , 2 While DOACs have improved stroke management, they can lead to adverse events, the most common of which is bleeding, which requires reversal of the anticoagulant effects by specific agents. Reversing the effects of VKAs is done with vitamin K, as well as with fresh frozen plasma and prothrombin complex concentrates.…”