Similar studies with NOACs in such patients are needed. 16. Edoxaban is 50% renally excreted and dosed once a day; it is not recommended in patients with end- stage renal disease or on dialysis.S4.1.1-11 Limited single-dose pharmacokinetic data have been published for rivaroxaban use in patients with end-stage kidney disease on dialysis.S4.1.1-59,S4.1.1-60 Dabigatran and rivaroxaban have been stud- ied by using prescription patterns in a dialysis Dabigatran and rivaroxaban were associated with a higher risk of hospi- talization or death from bleeding than that of 17. The RE-ALIGN trial (Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients After Heart Valve Replacement) was a multicenter, prospec- tive, randomized, phase II dose-validation study of dabigatran versus warfarin that enrolled patients (18-75 years of age) with one of the following: mechanical valve replacement in the aortic or mitral position (or both) within the prior 7 days (population A) or mechanical mitral valve (with or without aortic valve) replacement more than 3 months before randomization (population B). The trial was stopped after it had enrolled 252 patients because of unacceptable thromboembolic and bleeding event rates in the dabigatran group. Similar drug safety and efficacy information is lacking for mechanical CLINICAL STATEMENTS AND GUIDELINES heart valves and rivaroxaban, apixaban, and edoxaban. On the basis of the outcomes of the RE-ALIGN trial, the presence of a mechanical heart valve is considered a contraindication to all 4.2. Anticoagulant Options (Modified From Section 4.2., Antithrombotic Options, in the 2014 AF Guideline) 4.2.2.2. Non Vitamin K Oral Anticoagulants (Modified From Section 4.2.2.2., New Target-Specific Oral Anticoagulants, in the 2014 AF Guideline) Most NOACs represent an advance in therapeutic safety when compared with warfarin for prevention of throm- boembolism in patients with AF. 