Pros and cons of new oral anticoagulants

Abstract

The availability of new oral anticoagulants (NOACs) targeting either thrombin (dabigatran etexilate) or factor Xa (rivaroxaban and apixaban) for the prevention and treatment of thrombosis has been highly anticipated. NOACs have major pharmacologic advantages over vitamin K antagonists (eg, warfarin), including rapid onset/offset of action, few drug interactions, and predictable pharmacokinetics, eliminating the requirement for regular coagulation monitoring. Regulatory agencies have approved several NOACs for specific indications based on the results of clinical trials demonstrating efficacy and safety that are at least as good, if not better, than warfarin (for stroke prevention in atrial fibrillation and treatment and secondary prevention of venous thromboembolism) or low-molecular-weight heparin, which is injectable (for initial treatment of venous thromboembolism and thromboprophylaxis in patients undergoing hip or knee arthroplasty). However, the adoption of this new therapeutic class into clinical practice has been slower than expected due to several factors including concerns regarding medication adherence without laboratory monitoring, uncertainty about dosing in some patient populations (eg, renal dysfunction, marked extremes of body weight), and higher drug costs compared with warfarin. Other issues are the current absence of specific antidotes for NOACs and assays to measure drug levels at most centers. The indications for NOACs on the market will expand and at least one additional agent (edoxaban) will likely gain approval within the next 2 years. As practitioners gain familiarity with the drugs and healthcare systems adapt to their use, NOAC use will increase substantially over time. Warfarin, however, will continue to be an appropriate anticoagulant choice for many patients.

Rivaroxaban postmarketing risk of liver injury

“…Rivaroxaban is an oral direct factor Xa inhibitor that has been marketed worldwide since 2008 for the primary and secondary prevention and treatment of thromboembolic disorders [1,2]. Although liver injury was observed in premarketing trials of rivaroxaban [3], postmarketing cases of liver injury associated with rivaroxaban have not been published so far.…”

Determination of Apixaban Levels in Human Plasma by a High-Throughput Liquid Chromatographic Tandem Mass Spectrometry Assay / Determinarea rapidă a apixabanului în plasma umană prin cromatografie de lichide de înaltă performanță cuplată cu spectrometrie de masă în tandem

“…Because Apixaban is metabolized by the liver (partially by CYP 3A4) there are few recommendations to prescribe it to patients with hepatic impairment. No dosage adjustment of Apixaban is necessary in patient with mild hepatic impairment, but it should be used with cautions in patients with moderate liver disease (Child class Pugh A or B) and a discontinuation period up to 5 days can be considered before elective surgery in such patients [7]. The present clinical experience allows its administration in renal impairment with a creatinine clearance ≥ 15 ml/min.…”

“…The present clinical experience allows its administration in renal impairment with a creatinine clearance ≥ 15 ml/min. This is best done by calculating creatinine clearance using Cockcroft-Gault formula (some calculators are also available online), but with some adjustments regarding body-mass index [7]. Strong inhibitors or inducers of both CYP3A4 and P-glycoprotein can markedly influence the plasmatic concentrations of apixaban if co-administered [3].…”

“…Despite this feature, currently there are no warnings or recommendations regarding its use in special populations at high risk for developing venous thromboembolism (after gastric bypass surgery, lap-band weight loss surgery or extended resection of the small bowel) [7].…”

“…Moreover, it involves the administration of standard, indication-dependent, twice daily doses; it has a rapid onset of action (in 3 to 4 hours after oral intake maximum concentration Cmax is achieved) and decline of the anticoagulant effect (after intravenous administration a half-life of approximately 12 hours), with considerable fewer clinically significant drug interactions [3,5,11].…”