Comparison of Approaches for Stroke Prophylaxis in Patients with Non-Valvular Atrial Fibrillation: Network Meta-Analyses of Randomized Controlled Trials

Background: Multiple novel oral anticoagulants and left atrial appendage closure devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists in randomized controlled trials for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of these strategies are available from randomized controlled trials. We conducted the current analyses by combining efficacy and safety characteristics of all FDA approved stroke prophylaxis treatment strategies for patients with non-valvular atrial fibrillation. Materials and Methods We searched SCOPUS from 1945 till October 2015 for randomized controlled trials comparing these strategies and reporting efficacy and safety outcomes. Six randomized controlled trials were identified and included in the final analyses and review. We followed PRISMA guidelines for network meta-analyses while reporting the current analyses. We collected data on ischemic stroke, major bleeding, and the composite primary safety endpoint as defined by various randomized controlled trials. Network meta-analyses were conducted using consistency and inconsistency models for efficacy and safety outcomes. Surface under the cumulative ranking curve were then utilized to cluster rank these treatments for safety and efficacy. Results: Six randomized controlled trials with 59,627 patients comparing six treatment strategies were eligible for the analyses. All prophylaxis strategies had comparable rates of ischemic stroke. Apixaban was associated with the least number of primary safety endpoint events as compared with all other treatments. In the cluster analyses assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left atrial appendage closure device ranked last. Conclusions: Dose-adjusted vitamin K antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage closure devices are equally efficacious for ischemic stroke prevention but these treatments have different safety profiles. More randomized controlled trials are needed to directly compare these strategies

Initiation and outcomes with Class Ic antiarrhythmic drug therapy

Background: Expert opinion recommends performing exercise testing with initiation of Class Ic antiarrhythmic medication. Objective: To evaluate the rate and reason for discontinuation of Ic agent within the first year of follow up, with particular attention to rate of proarrhythmia and the value of routine treadmill testing. Methods: This is a single center retrospective cohort study including consecutive patients with atrial arrhythmias who were initiated on a Class Ic agent from 2011 to 2016. Data was collated from chart review and pharmacy database. Results: The study population included 300 patients (55% male, mean age 61; mean ejection fraction, 56%) started on flecainide (n = 153; 51%) and propafenone (n = 147; 49%). Drug initiation was completed while hospitalized on telemetry and the staff electrophysiologists directed dosing. There was one proarrhythmic event during initiation (0.3%). The primary reason for not being discharged on Ic agent was due to detection of proarrhythmia (n = 15) or ischemia (n = 1) with treadmill testing (5.3%). Exercise testing was the single significant variable to affect the decision to discontinue Ic drug, p < 0.0001 (95% CI: 1.89–6.08%). During follow up, the primary reason for discontinuation of Ic agent was lack of efficacy, 32%. Conclusions: With proper screening, initiation of Class Ic agent is associated with very low rate of proarrhythmia. Treadmill testing is of incremental value and should be completed in all patients after loading Class Ic antiarrhythmic. Keywords: Atrial fibrillation, Antiarrhythmic medication, Flecainide, Propafenone, Exercise stress testing, Proarrhythmi

Flow diagram for study selection in accordance with PRISMA guidelines.

<p>Flow diagram for study selection in accordance with PRISMA guidelines.</p

Baseline Medication Use of Included Trials.

<p>Baseline Medication Use of Included Trials.</p

Surface under the cumulative ranking curve plots for all treatments in the stroke prophylaxis network.

<p><i>Panel A</i>: Rankogram for Ischemic Stroke, <i>Panel B</i>: Rankogram for Major Bleeding, <i>Panel C</i>: Rankogram for Primary Safety Endpoint. <i>VKA = Dose-adjusted vitamin K antagonists</i>.</p

Interval plot for ischemic stroke in the stroke prophylaxis network.

<p><i>Panel A</i>: Ischemic Stroke, <i>Panel B</i>: Major Bleeding, <i>Panel C</i>: Primary Safety Endpoint. The solid black lines represent the confidence intervals for summary odds ratios for each comparison. The blue line is the line of no effect (odds ratio equal to 1). <i>VKA = Dose-adjusted vitamin K antagonists</i>.</p

Baseline Characteristics of Included Trials.

<p>Baseline Characteristics of Included Trials.</p