title: New oral anticoagulants: a review of the literature with particular emphasis on patients with impaired renal function.
abstract: Oral anticoagulant therapy (OAT) is widely used to prevent and treat thromboembolic events. Traditionally, warfarin has been the drug of choice and, indeed, this drug is effective and provides a more than 60% reduction in stroke risk in patients with atrial fibrillation. However, OAT entails an increased bleeding risk, and management of this is challenging. Among other things, new oral anticoagulant drugs offer fixed dosing, more predictable pharmacokinetics and fewer interactions with drugs and food. Moreover, these drugs seem to provide an improved benefit-risk ratio with respect to thromboembolic events and bleeding complications in a broad patient population. The new drugs differ from traditional OAT with respect to their mechanism of action and pharmacokinetics, especially with respect to elimination through the kidneys. These drugs may potentially cause bleeding complications in patients with reduced drug excretion due to impaired renal function. Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower. Pharmacokinetic studies and data from clinical studies have provided information on how to guide dosing in patients with renal impairment. However, the risk of drug accumulation and bleeding may be amplified by several drug-drug interactions. This article provides a review of the literature on the pharmacology of new anticoagulant drugs with particular focus on the impact of impaired renal function.
authors.affiliation: Department of Clinical Pharmacology, University Hospital of Aarhus, Aarhus, Denmark. bkz@farm.au.dk
authors.forename: Birgitte Klindt
authors.initials: BK
authors.lastname: Poulsen
authors.forename: Erik Lerkevang
authors.initials: EL
authors.lastname: Grove
authors.forename: Steen Elkjaer
authors.initials: SE
authors.lastname: Husted
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D004347:Drug Interactions; D018565:Food-Drug Interactions; D005919:Glomerular Filtration Rate; D006801:Humans; D008658:Inactivation, Metabolic; D007674:Kidney Diseases / Q000150:complications* / Q000378:metabolism; D013923:Thromboembolism / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants