Novel Oral Anticoagulants for DC Cardioversion Procedures: Utilization and Clinical Outcomes Compared with Warfarin.

BACKGROUND: Novel oral anticoagulant (NOAC) agents dabigatran, rivaroxaban, and apixaban are increasingly utilized as thromboembolic prevention for patients with atrial fibrillation undergoing direct current cardioversion (DCCV) with post hoc analyses of clinical trials suggesting satisfactory safety and efficacy. This study characterizes utilization, effectiveness, and complications of NOAC agents for stroke prophylaxis in the setting of DCCV. METHODS: Comparison of warfarin and NOAC agents as periprocedural anticoagulation for DCCV procedures performed at Cleveland Clinic from January 2009 through December 2013. Variables of interest include utilization rates for each NOAC agent stratified by clinical parameters including CHADS2 score, and associated clinical outcomes including cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral arterial embolism (PAE), and bleeding events during 8 weeks of postprocedure follow-up. RESULTS: Among 5,320 DCCV procedures, 673 (12.6%) cases were excluded due to inadequate follow-up. Warfarin was utilized in 3,721 (80.1%), dabigatran in 719 (15.5%), rivaroxaban in 159 (3.4%), and apixaban in 48 (1.0%) with a steady increase in NOAC utilization from 2011 to 2013. There were low rates of CVA/TIA (warfarin: 0.97% vs NOAC 1.62%, P = 0.162) and bleeding (warfarin: 1.02% vs NOAC: 0.5%, P = 0.247) and no significant differences detected between agents. Higher CHADS2 /CHA2 DS2 -VASC scores were associated with thromboembolic and bleeding risk. Increasing age, chronic kidney disease, diabetes, coronary disease, and deep vein thrombosis/pulmonary embolism were associated with increased bleeding risk. CONCLUSION: In a high-volume, single-center experience, NOAC utilization has grown to account for over a third of cardioversion procedures, and these agents appear safe and effective compared to warfarin with low rates of thromboembolic and bleeding complications.

Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists.

Preclinical studies suggest that compounds with dual norepinephrine reuptake inhibitor (NRI) and 5-HT(1A) partial agonist properties may provide an important new therapeutic approach to ADHD, depression, and anxiety. Reported herein is the discovery of a novel chemical series with a favorable NRI and 5-HT(1A) partial agonist pharmacological profile as well as excellent selectivity for the norepinephrine transporter over the dopamine transporter.