Ablation Versus Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation: A Meta-Analysis of Randomized Trials
2021; Lippincott Williams & Wilkins; Volume: 14; Issue: 8 Linguagem: Inglês
10.1161/circep.120.009692
ISSN1941-3149
AutoresBabikir Kheiri, Timothy F. Simpson, Ryle Przybylowicz, Miranda Merrill, Hani Alhamoud, Mohammed Osman, Khidir Dalouk, Eric C. Stecker, Charles A. Henrikson, Babak Nazer,
Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculation: Arrhythmia and ElectrophysiologyVol. 14, No. 8Ablation Versus Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation: A Meta-Analysis of Randomized Trials Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBAblation Versus Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation: A Meta-Analysis of Randomized Trials Babikir Kheiri, MD, MSc, MRCP Timothy F Simpson, MD, PharmD Ryle Przybylowicz, MD Miranda Merrill, MD Hani Alhamoud, MD Mohammed Osman, MD Khidir Dalouk, MD Eric Stecker, MD Charles A. Henrikson, MD, MPH Babak NazerMD Babikir KheiriBabikir Kheiri https://orcid.org/0000-0003-1747-2859 Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). , Timothy F SimpsonTimothy F Simpson https://orcid.org/0000-0002-8580-0773 Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). , Ryle PrzybylowiczRyle Przybylowicz https://orcid.org/0000-0002-1140-5164 Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). , Miranda MerrillMiranda Merrill https://orcid.org/0000-0002-3996-6350 Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). , Hani AlhamoudHani Alhamoud https://orcid.org/0000-0001-6439-6292 Division of Cardiology, West Virginia University School of Medicine, Morgantown (H.A., M.O.). , Mohammed OsmanMohammed Osman https://orcid.org/0000-0001-5097-5568 Division of Cardiology, West Virginia University School of Medicine, Morgantown (H.A., M.O.). , Khidir DaloukKhidir Dalouk Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). , Eric SteckerEric Stecker Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). , Charles A. HenriksonCharles A. Henrikson https://orcid.org/0000-0002-3381-8437 Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). and Babak NazerBabak Nazer Correspondence to: Babak Nazer, MD, Knight Cardiovascular Institute, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email E-mail Address: [email protected] https://orcid.org/0000-0002-4078-9064 Knight Cardiovascular Institute, Oregon Health & Science University, Portland (B.K., T.F.S., R.P., M.M., K.D., E.S., C.A.H., B.N.). Originally published16 Aug 2021https://doi.org/10.1161/CIRCEP.120.009692Circulation: Arrhythmia and Electrophysiology. 2021;14:e009692Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. In patients with symptomatic paroxysmal AF, current United States consensus guidelines recommend antiarrhythmic drugs (AADs) as the initial therapy for maintenance of sinus rhythm. However, given the substantial adverse effects of AADs and their limited efficacy in maintenance of sinus rhythm, catheter ablation is an attractive strategy. Therefore, we conducted a meta-analysis of all randomized controlled trials to evaluate the efficacy and safety of catheter ablation as initial therapy for patients with symptomatic paroxysmal AF.The authors declare that all supporting data are available within the article (and its supplementary files). We identified all randomized controlled trials and 3 authors (B.K., H.A., M.O.) extracted and analyzed the data using RevMan 5.3 and STATA v15.1 software. We calculated hazard ratios or risk ratios and their 95% CIs using a random-effects model. A unique Kaplan-Meier curve for trial-level treatment success was reconstructed and a Cox proportional-hazards model was calculated after testing the proportional-hazards assumption using the residual Schoenfeld test. Institutional Review Board approval was not required.We identified 5 randomized controlled trials1–5 which included 997 patients with paroxysmal AF without prior AADs use (mean age 57.3±10.8 years; 68.6% males; 40.6% with hypertension; 6.5% with coronary artery disease; 56.8% on anticoagulants; 52.5% on beta blockade; and the duration of AF was 1.3±2.4 years). The mean ejection fraction was 59.7±6.9%, and left atrium diameter was 39.6±5.8 mm. In the ablation group, the mean procedure duration was 139.1±68.7 minutes with 29.4±35.3 minutes of fluoroscopy time (cryoablation, n=258; radiofrequency ablation, n=244).In the AADs group, 34.1% crossed to ablation group after the blanking period. For the ablation group, 9.6% of the patients were placed on AADs beyond the blanking period, whereas 19.7% had a repeated ablation after the blanking period.Compared with AADs, ablation was associated with significantly reduced recurrence of any atrial tachyarrhythmia (risk ratio, 0.57 [95% CI, 0.43–0.75]; P<0.01), symptomatic recurrence (risk ratio, 0.45 [95% CI, 0.25–0.80]; P<0.01), and hospitalization (risk ratio, 0.33 [95% CI, 0.21–0.52]; P 0.05; Figure). Overall, ablation was associated with a low incidence of pericardial tamponade (0.8%), pulmonary venous stenosis (0.6%), and transient phrenic nerve palsy (0.8%). Meta-regression analysis of the primary outcome based on the duration of AF, left atrium diameter, ejection fraction, and age did not suggest any significant effect modifier. In addition, subgroup analysis showed no significant interaction between the ablation techniques (cryoablation versus radiofrequency ablation).Download figureDownload PowerPointFigure. Clinical outcomes of first-line catheter ablation versus anti-arrhythmic drug therapy for paroxysmal atrial fibrillation. Kaplan-Meier curve for treatment success (A) and Forest plot (B) for clinical outcomes. Kaplan-Meier estimates of trial-level treatment success defined as follows: RAAFT 2005, freedom from atrial fibrillation; RAAFT-2 (Radiofrequency Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment) 2014, freedom from any atrial tachyarrhythmias; STOP AF (Cryoballoon Catheter Ablation in Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) 2020, freedom from initial failure of the procedure, any subsequent atrial fibrillation surgery or ablation in the left atrium, or atrial arrhythmia recurrence, cardioversion, or use of class I or III antiarrhythmic drugs (AAD; ablation group only) outside the 90-d blanking period; EARLY AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) 2020, freedom from any atrial tachyarrhythmia. MANTRA-PAF indicates Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation; M-H, Mantel-Haenszel; RAAFT, Radiofrequency Ablation versus Antiarrhythmic Drugs for Atrial Fibrillation Treatment; and TIA, transient ischemic attack.In this meta-analysis of patients with symptomatic paroxysmal AF, we found that rhythm control strategy with up-front catheter ablation was associated with a significantly lower incidence of recurrent atrial tachyarrhythmias and hospitalization compared with AADs, and similar risk of death, stroke/transient ischemic attack, or serious side effects.AF is typically triggered by ectopic foci within the pulmonary veins. As AF progresses, significant atrial remodeling occurs which may lead to permanent atrial myopathy. As AF ablation techniques have evolved, interest in preventing these irreversible structural changes has grown, with the hope that preventing these changes may translate into meaningful clinical outcomes. However, guidelines recommend a trial of AADs as initial therapy. In our analysis, we observed a 43% reduction in recurrent atrial tachyarrhythmia, 55% reduction in symptomatic recurrence, and 67% reduction in all-cause hospitalizations with ablation over first-line AAD therapy (Figure). Notably, these trials generally included younger (mean 57.3 years) patients with early symptomatic AF episodes, preserved ejection fraction (mean 59.7%), and left atrium diameter <5.5 cm, excluding those with persistent or long-standing persistent AF. Nevertheless, these findings are promising and may inform first-line therapy recommendations in future guidelines.Limitations of this study include a small sample size and infrequent events. The lack of patient-level data prevented analysis of individual classes of AADs on AF recurrence and assessing functional endpoints. Moreover, the impact of high cross-over rate from AADs to ablation on clinical outcomes is not reported. Finally, long-term randomized controlled trials evaluating long-term efficacy are needed.We hope that the result of CRYO-FIRST trial (Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation; https://www.clinicaltrials.gov; Unique identifier: NCT01803438) provides further insights.In conclusion, among selected patients with symptomatic paroxysmal AF, catheter ablation as first-line rhythm control therapy was associated with lower incidence of atrial tachyarrhythmias recurrence and hospitalizations compared with AADs, with similar incidence of death, stroke/transient ischemic attack, and serious adverse effects.Sources of FundingNone.Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 787.Correspondence to: Babak Nazer, MD, Knight Cardiovascular Institute, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email [email protected]eduReferences1. Andrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, Roux JF, Yung D, Skanes A, Khaykin Y, et al.; EARLY-AF Investigators. Cryoablation or drug therapy for initial treatment of atrial fibrillation.N Engl J Med. 2021; 384:305–315. doi: 10.1056/NEJMoa2029980CrossrefMedlineGoogle Scholar2. Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, Niebauer M, Makati K, Halperin B, Gauri A, et al.; STOP AF First Trial Investigators. Cryoballoon ablation as initial therapy for atrial fibrillation.N Engl J Med. 2021; 384:316–324. doi: 10.1056/NEJMoa2029554CrossrefMedlineGoogle Scholar3. Morillo CA, Verma A, Connolly SJ, Kuck KH, Nair GM, Champagne J, Sterns LD, Beresh H, Healey JS, Natale A; RAAFT-2 Investigators. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial.JAMA. 2014; 311:692–700. doi: 10.1001/jama.2014.467CrossrefMedlineGoogle Scholar4. Cosedis Nielsen J, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Kongstad O, Pehrson S, Englund A, Hartikainen J, Mortensen LS, Hansen PS. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.N Engl J Med. 2012; 367:1587–1595. doi: 10.1056/NEJMoa1113566CrossrefMedlineGoogle Scholar5. Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D, Schweikert R, Brachmann J, Gunther J, et al.. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial.JAMA. 2005; 293:2634–2640. doi: 10.1001/jama.293.21.2634CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails August 2021Vol 14, Issue 8Article InformationMetrics Download: 496 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.120.009692PMID: 34397264 Originally publishedAugust 16, 2021 Keywordsrandomized controlled trialarrhythmiascatheter ablationmeta-analysisatrial fibrillationPDF download SubjectsArrhythmiasCatheter Ablation and Implantable Cardioverter-DefibrillatorAtrial Fibrillation
Referência(s)