a The 110-mg dose is not available in the United States. Unless the patient is elderly or has high bleeding risk or is taking p-glycoprotein inhibitors, where dabigatran 110 mg bid is preferred, except in the United States, where the 110-mg dose is not available. b Use 2.5 mg bid if 2 of 3 of the following criteria are present: age > 80 years, weight < 60 kg, or serum creatinine > 133 mmol/L. c In the United States, caution is advised when CrCl is > 95 mL/min. ESRD end-stage renal disease; RRT renal replacement therapy. (Adapted from Lau et al.437 ) See Figure 1 and 2 legends for expansion of other abbreviations. 1184 Evidence-Based Medicine [ 1 5 4 # 5 C H E S T N O V E M B E R 2 0 1 8 ] Remark: In patients with CKD who initiate OAC, concomitant antiplatelet therapy including low-dose aspirin is likely to substantially elevate bleeding risk and should be used very judiciously. AF With Associated Valvular Heart Disease A recent physician survey438 reported marked heterogeneity in the de nition of valvular and nonvalvular AF and variable management strategies, including NOACs in patients with valvular heart disease other than prosthetic heart valves or hemodynamically signi cant mitral stenosis. While hypertrophic cardiomyopathy is sometimes discussed in association with valvular AF, this will not be addressed in this section; speci c guidelines on this condition are available.439 The use of the term nonvalvular AF is unfortunate and misleading as patients with a wide range of valvular pathology and severity were enrolled in all of the phase 3 NOAC trials. The only valvular heart disease uniformly excluded from all the NOAC trials were signi cant (moderate or severe) mitral stenosis and mechanical heart valves. 