Current challenges and future prospects in oral anticoagulant therapy

Abstract

The choice for oral anticoagulant (OAC) therapy was previously limited to the vitamin K antagonists (VKAs). The advent of the direct oral anticoagulants (DOACs) brought with it the expectation that oral anticoagulation would become simpler (with the elimination of routine monitoring and introduction of a fixed-dose anticoagulant), and that the use of VKAs would be slowly phased out. Although DOACs have made anticoagulation more convenient and accessible, we are now faced with what can be described as a tyranny of choice, together with many unanswered questions relating to DOAC use. These include optimal DOAC selection and dosing, use in complex 'real-world' patients, the role for monitoring and issues surrounding adherence. Warfarin remains the anticoagulant of choice in certain scenarios (e.g. metallic heart valves). The future holds much excitement: clinical studies are underway to expand the indications for DOACs and experience continues to grow outside the trials setting.

Plasma contact factors as therapeutic targets

“…Direct oral anticoagulants (DOACs) are replacing vitamin K antagonists (VKAs) for treatment and prevention of thrombosis [1–5], particularly for acute venous thromboembolism (VTE) [6–8] and prevention of stroke in non-valvular atrial fibrillation [7,9,10]. VKAs such as warfarin exhibit narrow therapeutic windows and are subject to multiple drug-drug and dietary interactions, as well as pharmacogenetic considerations.…”

“…DOACs are attractive alternatives to VKAs. Several features of the thrombin inhibitor dabigatran etexilate and the factor Xa (FXa) inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban are appealing, including their safety profiles (notably reduced major bleeding, including intracranial hemorrhage [ICH]) [6], limited drug interactions, and predictable anticoagulant response without monitoring or dose adjustment [2,5,12]. However, DOACs have limitations.…”

Impact of proactive pharmacist‐assisted warfarin management using an electronic medication management system in Australian hospitalised patients

“…During the post‐intervention period, patient recruitment was slower than during the pre‐intervention period. This likely reflects the declining use of warfarin as more patients transition to newer DOACs, particularly for venous thromboembolic (VTE) conditions and atrial fibrillation . This evolving prescribing pattern also likely explains the change in the patient medical unit distribution between the time periods and the fact that more patients with mechanical valve replacements and fewer VTE patients were in the post‐intervention period.…”

“…Warfarin is a high‐risk medication with a narrow therapeutic index and high degree of intra‐ and inter‐patient variability in dose‐response. Despite recent advances with direct‐acting oral anticoagulants (DOACs), warfarin continues to have a role for specific patient groups to prevent and treat various thromboembolic conditions …”

Direct oral anticoagulants: peri‐operative considerations and controversies

“…Direct oral anticoagulants (DOAC) have a number of advantages over warfarin, such as: fixed dosing; no requirement for routine monitoring; predictable pharmacokinetics; fewer interactions; and a rapid onset/offset of clinical effect. Despite much enthusiasm for their use, there remain many challenges, such as: optimal drug and dose selection; their use in patients with a history of gastro‐intestinal bleeding; their reversal in the acute setting; and dosing at extremes of body weight . Although research on the management of DOACs in the peri‐operative period is increasing, knowledge among clinicians and formal guidance seems to be variable .…”