Anticoagulation for non-valvular atrial aibrillation – towards a new beginning with ximelagatran

Abstract

ObjectivesXimelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF).Materials and methodsWe provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF.ResultsAdjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 × normal) in 6% of patients.ConclusionsCurrent data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed.

Influence of Erythromycin on the Pharmacokinetics of Ximelagatran May Involve Inhibition of P-Glycoprotein-Mediated Excretion

“…With anticoagulant efficacy comparable to that of warfarin, currently the primary option for oral anticoagulation, ximelagatran differs from warfarin in having a predictable anticoagulant effect on coagulation assays that correlates closely with melagatran plasma concentrations and stable melagatran pharmacokinetics within and between patients, and in lacking the requirement for coagulation monitoring and lacking interactions with food, alcohol, and many commonly used medications (Bredberg et al, 2003;Eriksson et al, 2003c;Gustafsson and Elg, 2003;Johansson et al, 2003;Sarich et al, 2004a,b,c;Teng et al, 2004). On the basis of its efficacy and safety profiles, ximelagatran has been characterized as a possible alternative to warfarin which, although efficacious, is underutilized because of concerns about safety and tolerability (Boos and More, 2004;Donnan et al, 2004;Francis, 2004).…”

Rivaroxaban for treatment of intraventricular thrombus in Chagas disease

“…In 2004, the anticoagulant ximelagatran [7] was the first drug to try to substitute warfarin in non-valvular AF, but it was withdrawn from the market for hepatic toxicity. After that, three new drugs have been approved in this context, dabigatran [8], rivaroxaban, and apixaban [9].…”

Treatment and Prevention of Primary Intracerebral Hemorrhage

“…Several strategies for ICH prevention in patients undergoing chronic anticoagulation are on the horizon, including home INR machines to facilitate tight control of the INR and antithrombotic medications that do not need monitoring, such as direct thrombin inhibitors. [98][99][100][101] One such agent, ximelagatran, was shown to be comparable to warfarin for the prevention of stroke in patients with atrial fibrillation but was not approved by the Food and Drug Administration due to excess hepatotoxicity. 100,101 SECONDARY PREVENTION OF ICH Secondary prevention strategies differ depending on whether the index ICH was lobar or nonlobar.…”