Drug therapy in anticoagulation: which drug for which patient?

Abstract

Four non-vitamin K oral anticoagulants (NOACs) are now licensed and available in the UK, offering unprecedented choices in anticoagulant therapy for clinicians and patients. NOACs have many clear benefi ts over warfarin, the most striking being the reduction in intracranial haemorrhage. However, a number of uncertainties remain: their effi cacy in certain situations, utility of drug assays, signifi cance of drug interactions and management of bleeding. In the absence of any direct comparative trials, it is not clear that any of the NOACs is signifi cantly better than the others in any of the licensed indications. The differential activities, pharmacokinetics, metabolism, excretion and side effects of the agents should be considered when selecting the most appropriate anticoagulant. In this article, we discuss how, with careful selection for the relevant indication, NOACs can simplify therapy while improving outcomes. We aim to provide clinicians with the information needed to select the most suitable anticoagulant drug for an individual patient in a given situation. KEYWORDS : Anticoagulant therapy , non-vitamin K oral anticoagulants , NOACs IntroductionThe non-vitamin K oral anticoagulants (NOACs) 1 are now established in UK practice and new members continue to arrive. Within their licensed indications they have clear benefits over warfarin, but a number of uncertainties remain: efficacy in some specific situations, the utility of drug assays, significance of drug interactions and the management of bleeding all suffer from a paucity of data.This article provides an update on developments since the 2014 review in this journal.2 Our aim is to provide the information needed to select the most suitable anticoagulant drug for an individual patient in a given situation. ABSTRACTDrug therapy in anticoagulation: which drug for which patient? Properties of NOACsFour NOACs are now licensed and available in the UK: the direct factor Xa (FXa) inhibitors apixaban, edoxaban and rivaroxaban, and the direct thrombin inhibitor dabigatran. The key to best choice of agent lies in their individual pharmacokinetic profiles, metabolism and routes of excretion.

Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

“…Use of DOACs is contraindicated for patients with mechanical heart valves, and it is not recommended in severe renal insufficiency, patients with known cancer, and if there is concern for cost and drug compliance. DOACs should be avoided in patients with a body mass index above 40 kg/m [ 2 ] or those with body weight of over 120 kg [ 21 ]. Dabigatran, in particular, should additionally be avoided in moderate renal insufficiency, but is preferred in patients with a high stroke risk (when used at 150 mg twice a day dose) without renal dysfunction.…”

Management of venous thromboembolism with non–vitamin K oral anticoagulants: A review for nurse practitioners and pharmacists

“…Selecting an appropriate NOAC agent for eligible patients is challenging in the absence of direct comparative trials. However, considering agent pharmacokinetics, metabolism, and adverse effects can assist in the decision-making process (Millar & Laffan, 2017).…”

Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia

“…Within their licensed indications, DOACs have been shown to be at least as efficacious as warfarin and demonstrate some clear safety benefits over warfarin, in particular reducing the risk of intracranial haemorrhage. DOACs offer significant advantages to patients and doctors, and careful selection for the relevant indication can simplify therapy while improving outcomes in the general population [17]. Indeed, general European guidance recommends the use of DOACs over warfarin for stroke prevention in patients with nonvalvular AF [18], while UK NICE guidance recommends that the decision between DOAC and warfarin be based on the patient’s clinical features and preferences [19].…”

“…While bleeding is a recognised complication of DOACs in the general population, the incidence of intracranial and other significant major bleeding has generally been shown to be lower than for warfarin [17]. An important exception to this, and pertinent to the HHT population, is gastrointestinal bleeding, the incidence of which appears to vary considerably between DOACs.…”