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Systematic Review and Meta-analysis of the Efficacy of Cardioversion by Vernakalant and Comparators in Patients with Atrial Fibrillation

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Abstract

Purpose

Rate and rhythm control are two well established treatment objectives for atrial fibrillation (AF) patients. While symptom reduction is a primary treatment goal, therapeutic practice related to cardioversion varies by region and patient, with several precautions associated with the use of current therapies. No comprehensive literature review on the relative efficacy of existing cardioversion approaches compared to newly available therapies has been conducted.

Methods and results

A systematic literature review and meta-analysis were undertaken to evaluate the efficacy of pharmacologic therapies in eliciting cardioversion within 2 and 8–24 h among patients with recent-onset, short duration AF. Eligible studies included randomized controlled trials in which cardioversion rates were evaluated in at least 2 treatment groups. Bayesian mixed-treatment comparisons estimated odds ratios (95% credible intervals) for successful cardioversion. Results within 2 h showed vernakalant IV, propafenone IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24 h. Few adverse events were reported, with the most common being bradycardia and hypotension.

Conclusions

In pair-wise comparisons of active treatment arms to one another, results suggest vernakalant IV, propafenone IV and flecainide appear to be effective in achieving rapid cardioversion in patients with short duration AF compared to other agents. Application of these findings to clinical practice need to account for the variable comorbidity profiles of patients, important determinants in the selection of appropriate therapy for individual patients. Though best practice methods were used, further research comparing treatments through direct head-to-head comparisons may be warranted to confirm these findings and further inform clinical practice.

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Notes

  1. It should be noted that the higher odds ratio of 33.26 for vernakalant versus placebo was dictated by odds ratios from 3 individual studies of vernakalant versus placebo [41, 44, 50] as well as an indirect comparison derived from a study of vernakalant versus amiodarone [40]. Odds ratios for the 3 direct comparisons of vernakalant versus placebo ranged from 24 to 28, while a vernakalant versus amiodarone odds ratio of 19 and amiodarone versus placebo odds ratio of 1.9 in the fourth study corresponded to an indirect vernakalant versus placebo odds ratio of 37. Differences in the variance of the odds ratios in these 4 studies affected their impact in this analysis because the smallest cell counts were 1 and 3 in the vernakalant versus placebo studies and 6 in the vernakalant versus amiodarone study. This resulted in a smaller variance of the odds ratios in the vernakalant versus amiodarone study in comparison to the 3 vernakalant versus placebo studies, causing the indirect comparison of vernakalant versus placebo to have the same impact on the estimated odds ratio as the 3 direct comparisons in the vernakalant versus placebo studies, resulting in a higher meta-analyzed odds ratio for vernakalant versus placebo.

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  3. http://www.medicines.ie/medicine/14795/SPC/BRINAVESS+20%C2%A0mg+ml,+concentrate+for+solution+for+infusion/

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Acknowledgements

We would like to acknowledge Ronald B. Langdon for his assistance in manuscript preparation.

Funding Sources

Ms. Martin and Drs. Fahrbach, Avetisyan, and Mwamburi were full time employees of United BioSource, Inc. at the time this work was conducted; United BioSource Inc., received funding support by Merck and Company, Inc. for the work that was done.

Disclosures

Please note that Drs. Bash, Davies, and Phatak were full time employees of Merck and Company, Inc. at the time this work was conducted.

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Bash, L.D., Buono, J.L., Davies, G.M. et al. Systematic Review and Meta-analysis of the Efficacy of Cardioversion by Vernakalant and Comparators in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther 26, 167–179 (2012). https://doi.org/10.1007/s10557-012-6374-4

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