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Dronedarone and the Incidence of Stroke in Patients with Paroxysmal or Persistent Atrial Fibrillation

A Systematic Review and Meta-Analysis of Randomized Trials

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American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

Stroke is the most feared complication of atrial fibrillation (AF). Dronedarone is an antiarrhythmic drug with multichannel-blocking properties. Recently, a post hoc analysis of a large randomized trial has suggested a reduction of stroke risk in patients with paroxysmal or persistent AF receiving dronedarone.

Objective

We performed a systematic review and meta-analysis on the effect of dronedarone on the occurrence of stroke or transient ischemic attack (TIA) in patients with paroxysmal or persistent AF.

Methods

We searched PubMed, EMBASE, and ISI Web of Knowledge as well as abstracts of major conferences for randomized trials comparing dronedarone with placebo in patients with paroxysmal or persistent AF. The endpoint was the occurrence of stroke or TIA during follow-up. Fixed effect risk differences (RDs) were calculated with the Mantel-Haenszel method. We also performed random effects analysis with the DerSimonian Laird method.

Results

Four trials were included in the analysis; a total of 5967 patients were analyzed, 3183 receiving dronedarone 400 mg twice daily and 2784 receiving placebo. 160 strokes or TIAs were reported in the four trials: 67 in the dronedarone group (2.1%) and 93 in the placebo group (3.3%). In the fixed effect model, patients in the dronedarone group had a significantly lower risk for the occurrence of stroke or TIA during follow-up compared with patients in the placebo group. The RD of the incidence of stroke or TIA in all trials between patients randomized to dronedarone and those randomized to placebo was −0.0094 (95% confidence interval [CI] −0.0178, −0.0011; p = 0.027). The ATHENA trial had by far the highest statistical weight (79.5%). There was no evidence of heterogeneity (χ2 = 2.41, p = 0.300).

In the random effects model, the statistical weight of the ATHENA trial was much lower (45.1%) and the RD for stroke or TIA between the dronedarone and the placebo groups did not reach statistical significance (RD −0.0064, 95% CI −0.0144, 0.0016; p = 0.120).

Limitations

First, stroke was not a prespecified outcome measure in the included trials. Second, we did not analyze trials studying patients with permanent AF; very recent data show an adverse outcome in patients with permanent AF receiving dronedarone.

Conclusions

The meta-analysis indicates a reduced risk of stroke or TIA in patients with paroxysmal or persistent AF receiving dronedarone. These findings are largely due to the results of the ATHENA trial. Further research on this topic is necessary.

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References

  1. Hannon N, Sheehan O, Kelly L, et al. Stroke associated with atrial fibrillation: incidence and early outcomes in the north Dublin population stroke study. Cerebrovasc Dis 2010; 29: 43–9.

    Article  PubMed  Google Scholar 

  2. Camm AJ, Kirchhof P, Lip GY, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010; 31: 2369–429.

    Article  PubMed  Google Scholar 

  3. Connolly SJ, Crijns HJ, Torp-Pedersen C, et al. Analysis of stroke in ATHENA: a placebo-controlled, double-blind, parallel-arm trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular hospitalization or death from any cause in patients with atrial fibrillation/atrial flutter. Circulation 2009; 120: 1174–80.

    Article  PubMed  CAS  Google Scholar 

  4. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009; 62: 1006–12.

    Article  PubMed  Google Scholar 

  5. The Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. Julian PT Higgins, Sally Green, editors. Chapter 8 [online]. Available from URL: www.cochrane-handbook.org.

  6. Touboul P, Brugada J, Capucci A, et al. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Eur Heart J 2003; 24: 1481–7.

    Article  PubMed  CAS  Google Scholar 

  7. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007; 357: 987–99.

    Article  PubMed  CAS  Google Scholar 

  8. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 2009; 360: 668–78.

    Article  PubMed  CAS  Google Scholar 

  9. Davy JM, Herold M, Hoglund C, et al. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial fibrillation (ERATO) study. Am Heart J 2008; 156: 527.e1–9.

    Article  Google Scholar 

  10. Deaths doubled with dronedarone in PALLAS: FDA and EM A updates [online]. Available from URL: http://www.theheart.org/article/1255799/print.do [Accessed 2011 Aug 2].

Download references

Acknowledgments

There was no external funding for this work. The authors are solely responsible for the design and conduct of the study, the study analyses, and the manuscript. The analyzed trials were sponsored or supported by the drug manufacturer (EURIDIS/ADONIS and ATHENA by Sanofi-Aventis, and DAFNE by Sanofi-Synthelabo Recherche).

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Authors and Affiliations

  1. Second University Cardiology Department, University of Athens, Attikon University Hospital, Rimini 1, Haidari, 12462, Athens, Greece

    Nikolaos Dagres MD, Christos Varounis, Efstathios K. Iliodromitis, John P. Lekakis, Loukianos S. Rallidis & Maria Anastasiou-Nana

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  1. Nikolaos Dagres MD
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  2. Christos Varounis
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  3. Efstathios K. Iliodromitis
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  4. John P. Lekakis
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  5. Loukianos S. Rallidis
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Appendix 1

Appendix 1

Search Methodology

Databases

PubMed: PubMed was searched on 19 April 2011 with the search term ‘dronedarone[tiab] AND random*[tiab] AND atrial fibrillation[tiab]’. The search retrieved 27 results.

EMBASE: EMBASE was searched from 1974 to 13 April 2011 for the control terms ‘dronedarone’ or ‘dronedarone hydrochloride’ (each one of which retrieved 616 results), for the control term ‘atrial fibrillation’ (42 507 results), for the control term ‘clinical trial?’ (826 610 results) and for the control term ‘randomized controlled trial’ (280 590 results). The combination of these control terms yielded 33 results.

ISI Web of Knowledge: Web of Science was searched on 17 April 2011 for papers with the document type ‘article’ containing the title words ‘dronedarone’ and ‘atrial fibrillation’. The search retrieved 25 results.

Abstracts

Annual scientific sessions of the American Heart Association: We searched on the websites http://www.abstractsonline.com/arch/home.aspx?lookupkey=12345 (search term: ‘dronedarone’) and http://circ.ahajournals.org/search.dtl (search for abstracts containing the word ‘dronedarone’ in the title or the abstract body). The search retrieved ten results.

Annual scientific sessions of the Heart Rhythm Society: We searched on the website http://www.abstracts2view.com/hrs/index.php (search term: ‘dronedarone’). The search retrieved four results.

Annual scientific sessions of the American College of Cardiology: We searched on the website http://www.abstractsonline.com/plan/AdvancedSearch.aspx for the year 2010 and on the website http://www.abstractsonline.com/EPosterViewer/ListAll.aspx for the year 2011 (search term: ‘dronedarone’). For the years 2004–09, we searched the contents in the arrhythmia sections of the respective supplements of the Journal of the American College of Cardiology on the website http://www.sciencedirect.com for abstracts referring to dronedarone. The search retrieved five results.

Annual congresses of the European Society of Cardiology: We searched on the website http://spo.escardio.org/abstractbook/search.aspx for abstracts from the years 2005–2010 containing the word ‘dronedarone’ in the title. The search retrieved eight results.

All abstract searches were performed between 11 April and 1 May 2011.

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Dagres, N., Varounis, C., Iliodromitis, E.K. et al. Dronedarone and the Incidence of Stroke in Patients with Paroxysmal or Persistent Atrial Fibrillation. Am J Cardiovasc Drugs 11, 395–400 (2011). https://doi.org/10.2165/11594200-000000000-00000

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  • DOI: https://doi.org/10.2165/11594200-000000000-00000

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