Skip to main content

Main menu

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 Articles
  • Authors & Reviewers
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
    • Patient engagement
  • Members & Subscribers
    • Benefits for CMA Members
    • CPD Credits for Members
    • Subscribe to CMAJ Print
    • Subscription Prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2023
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN

User menu

Search

  • Advanced search
CMAJ
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN
CMAJ

Advanced Search

  • Home
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
    • COVID-19 Articles
  • Authors & Reviewers
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
    • Open access
    • Patient engagement
  • Members & Subscribers
    • Benefits for CMA Members
    • CPD Credits for Members
    • Subscribe to CMAJ Print
    • Subscription Prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2023
  • Visit CMAJ on Facebook
  • Follow CMAJ on Twitter
  • Follow CMAJ on Pinterest
  • Follow CMAJ on Youtube
  • Follow CMAJ on Instagram
Commentary

Antiarrhythmic drugs for atrial fibrillation: Do we need better use, better drugs or a randomized trial of ablation as primary therapy?

Stanley Nattel
CMAJ September 28, 2004 171 (7) 752-753; DOI: https://doi.org/10.1503/cmaj.1040853
Stanley Nattel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Responses
  • Metrics
  • PDF
Loading
  • © 2004 Canadian Medical Association or its licensors

Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice, and it contributes substantially to both morbidity and medical costs.1 In this issue Humphries and associates present an analysis of antiarrhythmic drug therapy for AF based on the Canadian Registry of Atrial Fibrillation (CARAF) (see page 741).2 The authors consider the use of flecainide, quinidine, sotalol, amiodarone and propafenone, and they note that a large proportion of patients who received these antiarrhythmic drugs had conditions that constitute drug-related contraindications or warrant warnings and precautions. They suggest that the results point to a need for safer drugs, with fewer contraindications, precautions and warnings, with which to treat AF. A number of important factors need to be considered when we analyze the results of this interesting and significant study.

The CARAF trial enrolled patients whose AF was diagnosed between 1991 and 1996. The results presented by Humphries and associates were obtained at baseline and at 3-month follow-up. Thus, most of the data reflect practices in use before 1996. The precautions, warnings and contraindications for the 5 antirrhythmic drugs studied are taken from the 1996 Compendium of Pharmaceuticals and Specialties (CPS), which was published after most treatment decisions had been made. Although most of the information might have applied in earlier versions of the CPS, this does not appear to have been assessed, which presents a limitation of the analysis.

The characteristics of the patient population also need to be considered. The study was limited to patients with paroxysmal AF, for which heart-rate control is particularly difficult,3 making sinus-rhythm maintenance more often a primary objective. In addition, the vast majority of patients (83%) were symptomatic at first presentation, which further justified the use of antiarrhythmic drugs to prevent AF recurrence. Given the decision to use an antiarrhythmic drug, an examination of the list of precautions, warnings and contraindications in Table 1 of the research article2 makes it clear that the results of the survey could hardly have been otherwise. For example, heart failure, a history of myocardial infarction and concomitant digoxin use are cautioned for all 5 drugs studied, and according to Table 22 were present in 15% (at baseline), 20% (at baseline) and 46% (at 3 months) of the patient population respectively. The number of common conditions that are cautioned for each drug in Table 1 is so large that for many patients it was likely impossible to find any drug that did not involve a contraindication, warning or precaution. The authors recognize this and are careful to state that the use of antiarrhythmic agents may have reflected appropriate and judicious choices on the part of treating physicians. They note that a post hoc assessment of adverse events did not identify an association with medication use.

An additional and crucial point to consider is the changing context within which we view treatment of AF. Enrollment and data-gathering for the study by Humphries and associates were largely conducted between 1991 and 1996. The AFFIRM4 and RACE5 studies published last year demonstrated equivalent outcomes for rate and rhythm control approaches and emphasized the risks of the use of antiarrhythmic drugs for rhythm control (e.g., proarrhythmia, drug-specific adverse effects, risk of thromboembolic stroke if oral anticoagulants stopped, etc.). Radiofrequency ablation approaches to managing AF emerged in the second half of the 1990s. The strategy of atrioventricular nodal ablation and permanent pacemaking was found to produce an excellent symptomatic result in patients who are refractory to drugs, particularly those with paroxysmal AF.6 More recently, the elaboration of effective ablation procedures directed toward the pulmonary vein region of the left atrium have resulted in apparent “cure” rates of > 80%.7,8 These major developments condition how we see the results of the study by Humphries and associates but obviously could not have affected physician judgement at the time that the CARAF data were being obtained. The real question, however, is not how we judge antiarrhythmic drug use in 1991–1996 by today's standards, but what the implications of this study are for current medical practice in light of our present knowledge and capabilities.

Physicians are obviously better equipped to make decisions about AF management today than they were in the early 1990s. In the light of AFFIRM and RACE, asymptomatic patients should rarely, if ever, receive antiarrhythmic drugs for sinus rhythm maintenance. It is very likely that the follow-up study to CARAF, CARAF II,2 will show the expected tendency toward reduced antiarrhythmic drug usage in AF.

In light of the great efficacy of nonpharmacological ablation-based therapies for AF,6,7,8 one cannot help but wonder whether such invasive approaches should be situated earlier in the therapeutic decision tree for many patients. In fact, in view of the high reported cure rates for paroxysmal AF treated with catheter-based radiofrequency pulmonary vein isolation ablation,7,8this is perhaps the time for a randomized trial of ablation versus standard medical therapy as a primary approach to symptomatic patients with recurrent paroxysmal AF.

Humphries and associates mention the potential interest of new and improved antiarrhythmic drugs for AF. Certainly, drugs with fewer contraindications and greater safety would be valuable. Targeting atrial-specific ion channels and developing antiarrhythmic drugs with selected channel-blocking profiles are very attractive approaches,9,10 but their practical value and applicability for AF have yet to be confirmed. Recent developments in understanding the pathophysiology of AF make targeting the AF substrate an interesting possibility.11,12 Success in preventing components of AF pathophysiology,13,14,15,16 including the prevention of AF-promoting structural remodelling by suppressing renin–angiotensin activation,13,14 has been achieved in animal experiments. Clinical trials indicate the potential value of inhibiting angiotensin-converting enzyme17,18,19 or blocking angiotensin type-1 receptors20 in preventing AF recurrence.

The study by Humphries and associates sensitizes us to the limitations inherent in choosing currently available antiarrhythmic drugs for AF therapy. It also points to the fact that our choices for AF therapy may be much more informed and richer in 2004 than they were in 1994. There is hope for drug therapy that targets the atria without risk of adverse effects on the ventricles and that prevents AF at the level of substrate development. A serious look needs to be taken at the possibility that ablation approaches may be better choices for many patients with AF than currently available antiarrhythmic agents. One can't help but think that the best way to take that look would be in the context of a well-designed prospective randomized clinical trial.

𝛃 See related article page 741

Footnotes

  • Competing interests: None declared.

References

  1. 1.↵
    Stewart S, Murphy N, Walker A, McGuire A, McMurray JJ. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart 2004;90:286-92.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    Humphries KH, Kerr CR, Steinbuch M, Dorian P, for the Canadian Registry of Atrial Fibrillation (CARAF) Investigators. Limitations to antiarrhythmic drug use in patients with atrial fibrillation. CMAJ 2004;171(7):741-5.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    Nattel S, Ehrlich JR. Chapter 56. Atrial Fibrillation. In: Zipes DP, Jalife J, editors. Cardiac electrophysiology, from cell to bedside. 4th ed. Philadelphia: W.B. Saunders; 2004. p. 512-23.
  4. 4.↵
    Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators: a comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825-33.
    OpenUrlCrossRefPubMed
  5. 5.↵
    Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al. Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group: a comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002; 347: 1834-40.
    OpenUrlCrossRefPubMed
  6. 6.↵
    Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA. Clinical outcomes after ablation and pacing therapy for atrial fibrillation : a meta-analysis. Circulation 2000;101:1138-44.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, et al. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation 2001;104:2539-44.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    Oral H, Scharf C, Chugh A, Hall B, Cheung P, Good E, et al. Catheter ablation for paroxysmal atrial fibrillation: segmental pulmonary vein ostial ablation versus left atrial ablation. Circulation 2003;108:2355-60.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    Nattel S, Yue L, Wang Z. Cardiac ultrarapid delayed rectifiers: a novel potassium current family of functional similarity and molecular diversity. Cell Physiol Biochem 1999;9:217-26.
    OpenUrlCrossRefPubMed
  10. 10.↵
    Nattel S. The molecular and ionic specificity of antiarrhythmic drug actions. J Cardiovasc Electrophysiol 1999;10:272-82.
    OpenUrlCrossRefPubMed
  11. 11.↵
    Nattel S. Therapeutic implications of atrial fibrillation mechanisms: can mechanistic insights be used to improve AF management? Cardiovasc Res 2002; 54:347-60.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res 2002;54:230-46.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    Li D, Shinagawa K, Pang L, Leung TK, Cardin S, Wang Z, et al. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation 2001;104:2608-14.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    Kumagai K, Nakashima H, Urata H, Gondo N, Arakawa K, Saku K. Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003;41:2197-204.
    OpenUrlCrossRefPubMed
  15. 15.↵
    Fareh S, Benardeau A, Thibault B, Nattel S. The T-type Ca(2+) channel blocker mibefradil prevents the development of a substrate for atrial fibrillation by tachycardia-induced atrial remodeling in dogs. Circulation 1999; 100: 2191-7.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    Shinagawa K, Shiroshita-Takeshita A, Schram G, Nattel S. Effects of antiarrhythmic drugs on fibrillation in the remodeled atrium: insights into the mechanism of the superior efficacy of amiodarone. Circulation 2003;107:1440-6.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    Pedersen OD, Bagger H, Kober L, Torp-Pedersen C. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999;100:376-80.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    Vermes E, Tardif JC, Bourassa MG, Racine N, Levesque S, White M, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials. Circulation 2003;107:2926-31.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    Ueng KC, Tsai TP, Yu WC, Tsai CF, Lin MC, Chan KC, et al. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J 2003;24:2090-8.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation 2002; 106: 331-6.
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top

In this issue

Canadian Medical Association Journal: 171 (7)
CMAJ
Vol. 171, Issue 7
28 Sep 2004
  • Table of Contents
  • Index by author

Article tools

Respond to this article
Print
Download PDF
Article Alerts
To sign up for email alerts or to access your current email alerts, enter your email address below:
Email Article

Thank you for your interest in spreading the word on CMAJ.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Antiarrhythmic drugs for atrial fibrillation: Do we need better use, better drugs or a randomized trial of ablation as primary therapy?
(Your Name) has sent you a message from CMAJ
(Your Name) thought you would like to see the CMAJ web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Antiarrhythmic drugs for atrial fibrillation: Do we need better use, better drugs or a randomized trial of ablation as primary therapy?
Stanley Nattel
CMAJ Sep 2004, 171 (7) 752-753; DOI: 10.1503/cmaj.1040853

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
‍ Request Permissions
Share
Antiarrhythmic drugs for atrial fibrillation: Do we need better use, better drugs or a randomized trial of ablation as primary therapy?
Stanley Nattel
CMAJ Sep 2004, 171 (7) 752-753; DOI: 10.1503/cmaj.1040853
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Footnotes
    • References
  • Responses
  • Metrics
  • PDF

Related Articles

  • Highlights of this issue
  • Limitations to antiarrhythmic drug use in patients with atrial fibrillation
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Antiracism as a foundational competency: reimagining CanMEDS through an antiracist lens
  • Keeping the front door open: ensuring access to primary care for all in Canada
  • Improving post-tuberculosis care in Canada
Show more Commentary

Similar Articles

Collections

  • Topics
    • Cardiology: arrhythmias

 

View Latest Classified Ads

Content

  • Current issue
  • Past issues
  • Collections
  • Sections
  • Blog
  • Podcasts
  • Alerts
  • RSS
  • Early releases

Information for

  • Advertisers
  • Authors
  • Reviewers
  • CMA Members
  • CPD credits
  • Media
  • Reprint requests
  • Subscribers

About

  • General Information
  • Journal staff
  • Editorial Board
  • Advisory Panels
  • Governance Council
  • Journal Oversight
  • Careers
  • Contact
  • Copyright and Permissions
  • Accessibiity
  • CMA Civility Standards
CMAJ Group

Copyright 2023, CMA Impact Inc. or its licensors. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p)

All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association or its subsidiaries.

To receive any of these resources in an accessible format, please contact us at CMAJ Group, 500-1410 Blair Towers Place, Ottawa ON, K1J 9B9; p: 1-888-855-2555; e: cmajgroup@cmaj.ca

Powered by HighWire