Apples and Oranges
2008; Lippincott Williams & Wilkins; Volume: 118; Issue: 24 Linguagem: Inglês
10.1161/circulationaha.108.823179
ISSN1524-4539
Autores Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculationVol. 118, No. 24Apples and Oranges Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBApples and OrangesComparing Antiarrhythmic Drugs and Catheter Ablation for Treatment of Atrial Fibrillation David J. Callans David J. CallansDavid J. Callans From the Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia. Originally published9 Dec 2008https://doi.org/10.1161/CIRCULATIONAHA.108.823179Circulation. 2008;118:2488–2490Since the initial proof of concept that catheter ablation could prevent recurrent atrial fibrillation (AF), there has been a considerable evolution in the focus of studies to evaluate this therapy. Initial studies were typically single center and aimed at ablation of paroxysmal AF in healthy young patients, with a relatively superficial end point of absence of recurrent symptomatic AF (ie, monitoring was minimal) in short term follow up. Technique was emphasized, with each group trumpeting the superiority of the lesion strategy of the day. Through this experience, procedural complications have decreased and attention has been directed gradually to patients with more-established AF. Guidelines have been developed1,2 to attempt to enforce more uniform descriptions of complications and success, with a focus on extensive monitoring for asymptomatic recurrence.Article p 2498Having demonstrated that ablation can provide short term-control of AF in well-selected patients with an acceptable risk of serious complications (at least in experienced centers), we are now in the second wave of evaluation of AF ablation: comparing ablation to antiarrhythmic drugs in various clinical situations. Although not without precedent, comparing interventional and medical therapy is difficult. Any proper comparison would measure both differential efficacy and risk. It is easy to identify serious complications of interventions; serious complications of medical therapy are rare and hard to recognize, particularly over the short duration of clinical trials.In this context, the study by Jaïs and coworkers is an important step forward.3 Patients with documented paroxysmal AF for at least 6 months who had failed at least 1 antiarrhythmic drug were randomized to treatment with a new antiarrhythmic drug (or combination of drugs) or catheter ablation. A 90-day treatment stabilization period allowed for the performance of up to 3 ablation procedures or 3 changes in antiarrhythmic therapy. The primary end point was the absence of recurrent AF (atrial arrhythmias >3 minutes, whether symptomatic or detected by monitoring) from months 3 to 12. Additional end points included time to AF recurrence, complications and adverse events, quality of life, exercise capacity, AF burden, and the success of amiodarone when naïve patients were treated. Patients were treated with new antiarrhythmic drugs, chosen at the discretion of their personal physician from 8 drugs including amiodarone, as well as drug combinations. Ablation was usually performed with a strategy of pulmonary vein isolation and cavotricuspid isthmus ablation; left atrial ablation with verification of bidirectional block and ablation of non-pulmonary vein foci were performed at the discretion of the treating physician. Patients were monitored with 24-hour Holter recordings at baseline and at 3, 6, and 12 months.One-hundred twelve patients were enrolled, aged 51.1±11.1 years, having failed 2±1 antiarrhythmic drugs. In the drug arm, 59 patients received a mean of 2.5±1 drug trials including combination therapy in all patients and amiodarone in 35 patients. At 1 year, 13/55 (23%) were free of atrial arrhythmias. Thirty-seven patients crossed over to ablation therapy; in the 22 patients who did not cross over, amiodarone was used for the first time in 18 and failed in 12 patients (66%). In the ablation arm, 53 patients received a mean of 1.8±0.8 procedures. Forty six of 52 patients (89%) were free from recurrent AF without antiarrhythmic drugs at 1 year (P<0.0001 compared with drug treatment). The ablation group had a greater reduction in AF burden and improvement in quality of life and exercise performance compared with the antiarrhythmic drug group; no difference was found in the affect of ablation versus drugs on change in left atrial size or ejection fraction. Three serious (2 pericardial effusions requiring percutaneous drainage, 1 PV stenosis requiring stenting; 1.9%) and 2 less dramatic (groin hematomas) complications were observed in 155 ablation procedures (including crossovers). One patient treated with antiarrhythmic drugs had hyperthyroidism and 2 died of causes that were deemed unrelated to therapy. The authors conclude that "catheter ablation of AF is superior to antiarrhythmic drug therapy in patients with paroxysmal AF who have previously taken and failed antiarrhythmic drugs."The authors point out that antiarrhythmic drugs have a worse efficacy in this trial than might be expected from previous trials. Despite multiple attempts, and although AF burden was reduced in both groups, only 23% of patients were free from AF recurrence at 1 year. Even amiodarone, when administered to patients who had not been previously treated with this agent resulted in a disappointing 34% success rate. As discussed, this disconnect with the expected success rates based on published trials is multifactorial. Using the Canadian Trial of Atrial Fibrillation as an example (CTAF),4 patients in antiarrhythmic drug studies are generally older (65±11 years), more likely to be persistent (54%) and generally thought to be less symptomatic. Patients in CTAF were equipped with a transtelephonic monitor and instructed to transmit with symptoms, but this arrangement is fairly unique for antiarrhythmic drug studies. Overall, the level of surveillance relative to AF recurrence has been much more stringent in contemporary studies of catheter ablation than in drug studies. In the present study, the failure of an average of 2 antiarrhythmic drugs before study entry may have also preselected a group more prone to drug failure.The present results are in keeping with prior randomized comparisons of ablation and antiarrhythmic drug therapy.5–7 In general, these studies have been small but have adhered to the rigor of posttreatment monitoring and well-defined end point criteria at 1 year. Patients in these trials have been relatively young (weighted average age in the 4 trials, 56.3 years) and healthy and, in most cases, have had paroxysmal AF. All of these trials save one required antiarrhythmic drug failure before entry; the Radiofrequency Ablation versus Antiarrhythmic Drugs as First-line Treatment of Symptomatic Atrial Fibrillation (RAAFT) evaluated first therapy for paroxysmal AF. All trials demonstrated that ablation therapy was significantly more effective than antiarrhythmic therapy; in the Catheter Ablation for the Cure of Atrial Fibrillation study (CACAF), catheter ablation plus antiarrhythmic drugs was compared with antiarrhythmic drugs alone (Figure 1). In all of these trials, the serious complications of catheter ablation have been modest (0 to 4.4%), in keeping with performance in highly experienced centers. Download figureDownload PowerPointFigure. Four randomized trials of catheter ablation versus antiarrhythmic drugs for AF, arranged roughly according to duration of AF. Freedom from recurrent AF at 1 year is reported without effect of crossover after a single ablation procedure (except in A4, in which repeat procedures within 3 months were prespecified) and without the effect of concomitant antiarrhythmic drug use in the ablation group (except in CACAF, which was by design). A4 indicates Catheter Ablation versus Antiarrhythmic Drugs for Atrial Fibrillation; APAF, Circumferential Pulmonary Vein Ablation versus Antiarrhythmic Drug Therapy in Paroxysmal Atrial Fibrillation.The authors should be congratulated for this important contribution. Taken in perspective with the other randomized trials, it is unquestionable that ablation therapy is more effective than antiarrhythmic drugs, at least in young mostly healthy patients and when performed by highly skilled practitioners. Another randomized trial suggested reasonable efficacy of ablation in patients with longstanding persistent AF.8 Recent observational studies have demonstrated effectiveness of ablation over that which would have been expected of drug therapy in patients with heart failure9,10 and in elderly patients,11 suggesting a more widespread treatment benefit.However, this is about as far as the second wave can take us. It is unquestionable that ablation in more effective, but it is impossible to conclude that it is superior to drug therapy using the studies that have been performed. Part of the problem, as mentioned above, is that it is difficult to factor in the difference between potentially dramatic procedural complications and more mundane side effects of drug therapy. In the first worldwide survey of catheter ablation for AF, major complications, including death (0.05%) and stroke (0.28%), were observed in 6% of 11 762 procedures.12 Potential for underreporting aside, these data provide the best impression to date of the more widespread use of catheter ablation outside of expert centers. Although serious complications seem to be decreasing with time, some incidence will always be seen with any interventional approach. On the other hand, most experts admit the potential for a negative effect of antiarrhythmic drug therapy on mortality, largely on the basis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial.13 These effects are unlikely to be captured in short-term trials in relatively well patients, who are almost certainly not as likely to be compromised as older AFFIRM-type patients.Even more importantly, trials to date have not accounted for the most powerful effect on mortality, that of the AF disease process itself.14 The question of whether ablation can reclaim some of the adverse effect on mortality caused by AF is untested and will require large studies of long duration. The proposed Catheter ABlation versus ANtiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) study, a randomized trial of ablation versus drug therapy (rate or rhythm control) in AFFIRM-type patients, will be an excellent first step. Entirely different (and much more difficult to answer) questions will be evaluated in the "third wave" of research on AF ablation. Does ablation permanently arrest (allowing for patient recovery) the otherwise inexorably progressive atrial remodeling and fibrosis caused by AF? If so, is there a given AF duration beyond which ablation therapy is unlikely to be helpful? Is ablation, when acutely successful, reasonably permanent, even with regard to senescent AF? If so, does it eliminate the risk of AF-related thromboembolism and the associated need for and risk of warfarin anticoagulation? Can ablation be performed without significant negative long-term affects on left atrial performance? Can such a procedure be widely applied in a cost-effective manner? Novel ideas for increased cooperation, not to mention funding, will be required to answer questions of this magnitude, particularly because these questions develop slowly, over the course of a human lifetime.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.DisclosuresNone.FootnotesCorrespondence to David J. Callans, MD, Hospital of the University of Pennsylvania, Cardiovascular Division, 9.129 Founders Pavilion, 3400 Spruce St, Philadelphia, PA 19104. E-mail [email protected] References 1 Natale A, Raviele A, Arentz T, Calkins H, Chen S, Haissaguerre M, Hindricks G, Ho Y, Kuck K, Marchlinski F, Napolitano C, Packer D, Pappone C, Prystowsky E, R. S., Shah D, Themistoclakis S, Verma A. Venice Chart international consensus document on atrial fibrillation ablation. J Cardiovasc Electrophysiol. 2007; 18: 560–580.CrossrefMedlineGoogle Scholar2 Calkins H, Brugada J, Packer D, Cappato R, Chen S, Crijns H, Damiano RJ, Davies D, Haines D, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H, Kuck K, Lindsay B, Marchlinski F, McCarthy P, Mont J, Morady F, Nademanee K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin J, Shemin R. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up: a report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 2007; 8: 816–861.Google Scholar3 Jaïs P, Cauchemez B, Macle L, Daoud E, Khairy P, Subbiah R, Hocini M, Extramiana F, Sacher F, Bordachar P, Klein G, Weerasooriya R, Clémenty J, Haïssaguerre M. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: the A4 study. Circulation. 2008; 118: 2498–2505.LinkGoogle Scholar4 Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert J, Dubuc M, Gagne P, Nattel S, Thibault B. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med. 2000; 342: 913–920.CrossrefMedlineGoogle Scholar5 Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D, Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R, Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005; 293: 2634–2640.CrossrefMedlineGoogle Scholar6 Stabile G, Bertaglia E, Senatore G, De Simone A, Zoppo F, Donnici G, Turco P, Pascotto P, Fazzari M, Vitale D. 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N Engl J Med. 2006; 354: 934–941.CrossrefMedlineGoogle Scholar9 Hsu L, Jais P, Sanders P, Garrigue S, Hocini M, Sacher F, Takahashi Y, Rotter M, Pasquie J, Scavee C, Bordachar P, Clementy J, Haïssaguerre M. Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med. 2004; 351: 2373–2383.CrossrefMedlineGoogle Scholar10 Gentlesk P, Sauer W, Gerstenfeld E, Lin D, Dixit S, Zado E, Callans D, Marchlinski F. Reversal of left ventricular dysfunction following ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2007; 18: 9–14.CrossrefMedlineGoogle Scholar11 Zado E, Callans D, Riley M, Hutchinson M, Garcia F, Bala R, Lin D, Cooper J, Verdino R, Russo A, Dixit S, Gerstenfeld E, Marchlinski F. Long-term clinical efficacy and risk of catheter ablation for atrial fibrillation in the elderly. J Cardiovasc Electrophysiol. 2008; 19: 621–626.CrossrefMedlineGoogle Scholar12 Cappato R, Calkins H, Chen S, Davies W, Iesaka Y, Kalman J, Kim Y, Klein G, Packer D, Skanes A. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation. 2005; 111: 1100–1105.LinkGoogle Scholar13 Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, Josephson RA, Kellen JC, Klein RC, Krahn AD, Mickel M, Mitchell LB, Nelson JD, Rosenberg Y, Schron E, Shemanski L, Waldo AL, Wyse DG; AFFIRM Investigators. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study. Circulation. 2004; 109: 1509–1513.LinkGoogle Scholar14 Beyerbach D, Zipes D. Mortality as an endpoint in atrial fibrillation. 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December 9, 2008Vol 118, Issue 24 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.108.823179PMID: 19064689 Originally publishedDecember 9, 2008 KeywordsEditorialsablationatrial fibrillationantiarrhythmia agentsPDF download Advertisement SubjectsArrhythmiasCatheter Ablation and Implantable Cardioverter-Defibrillator
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