Catheter Ablation vs Antiarrhythmic Agents in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis

Catheter Ablation vs Antiarrhythmic Agents in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Catheter Ablation vs Antiarrhythmic Agents in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis Joshuan J. Barboza, Francisco D. Paz, Christian D. Saldaña, Miguelangel S. Ayca, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7820043/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with increased morbidity and mortality. While catheter ablation and antiarrhythmic drug (AAD) therapy are both established treatment options, their comparative efficacy and safety remain debated. Objective This systematic review and meta-analysis evaluated the effectiveness and safety of catheter ablation versus AAD therapy in adults with AF. Methods A comprehensive search of PubMed, Scopus, Embase, and Web of Science was conducted for randomized controlled trials (RCTs) comparing catheter ablation (radiofrequency or cryoballoon) with AAD therapy. Primary outcomes included atrial arrhythmia recurrence and progression to persistent AF. Secondary outcomes encompass serious adverse events, reintervention rates, and procedure-related complications. Risk of bias was assessed using the RoB 2.0 tool, and certainty of evidence was evaluated using the GRADE framework. Results A total of 24 RCTs involving 9,507 patients were included. Catheter ablation significantly reduced atrial arrhythmia recurrence (RR: 0.57; 95% CI: 0.44–0.73) and progression to persistent AF (RR: 0.12; 95% CI: 0.06–0.24). No difference in serious adverse events was observed between groups (RR: 1.00; 95% CI: 0.84–1.19). However, catheter ablation was associated with a higher risk of reintervention (RR: 36.04; 95% CI: 16.10–80.65) and procedure-related complications (RR: 8.52; 95% CI: 3.12–23.27). Side effects were significantly lower in the ablation group than in AAD therapy (RR: 0.04; 95% CI: 0.01–0.10). Conclusions Catheter ablation demonstrates superior efficacy in reducing arrhythmia recurrence and preventing progression to persistent AF, with a comparable safety profile to AAD therapy. However, the increased risk of reintervention and procedural complications highlights the need for careful patient selection and shared decision-making. Anti-Arrhythmia Agents Atrial Fibrillation Catheter Ablation. (MESH) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 INTRODUCTION Atrial fibrillation (AF), as the most frequent sustained cardiac dysrhythmia in the adult population, is characterized by rapid and disorganized atrial activation, which, if not diagnosed in time, can lead to serious complications such as stroke and heart failure, including death ( 1 , 2 ). Its prevalence is increasing, affecting millions of adults, and the various clinical complications affect the quality of life not only at the personal level, but also at the family and social levels ( 3 ). Over the years, multiple management strategies have been developed for this type of supraventricular arrhythmia, including pharmacological therapy and surgical interventions such as catheter ablation, which offer both benefits and risks for the health of sufferers ( 4 ). However, the choice between pharmacological therapy vs. catheter ablation therapy is under discussion, because for years, pharmacological therapy has been the first management option before considering ablation ( 5 ). Despite this, in recent years several randomized clinical trials have been carried out, which directly compare pharmacological therapy vs catheter ablation, demonstrating that the latter generates a reduction in the recurrence of arrhythmias, thus improving the quality of life of individuals, providing greater cost/benefit with a lower rate of adverse events and a lower rate of treatment abandonment ( 6 , 7 ). It should be noted that it is not only about controlling the disease and its recurrences, but also about generating impact on the quality of life, how a pharmacological strategy vs. ablation affects the reduction of the burden of atrial fibrillation, as well as to see how it impacts on other comorbidities, if these improve or worsen with the implementation of specific management ( 8 , 9 ). Therefore, atrial fibrillation negatively affects the quality of life of the population, also shortening their years of life, so the option of rhythm control vs. heart rate control can generate a reduction in the burden of atrial fibrillation, and thus improve the quality of life ( 10 ). The present systematic review and meta-analysis aim to analyze the most updated and contrasted evidence on the efficacy and safety of catheter ablation compared to antiarrhythmic therapy (different drugs will be analyzed: beta-blockers, amiodarone, propafenone, among others) in patients with Atrial Fibrillation. Studies such as clinical trials and systematic reviews with meta-analysis are included to provide a detailed analysis of the advantages and limitations of each therapeutic strategy, as well as the evaluation of changes in quality of life, adverse side effects, and mortality cases. METHODS This study was a systematic review with meta-analysis. The reference elements for systematic reviews and meta-analyses (PRISMA-2020) informed this review. This protocol was registered in PROSPERO database (CRD42025635074). Searches This research used PubMed, Scopus, the Web of Science, and Embase databases. The searches were carried out starting September 29, 2024. Keywords, MeSH terms (PubMed), and Entree thesaurus terms (Scopus, Embase) were included in this review. Subsequently, a search strategy was applied to each database (Supplemental Table 1). The primary phrases used in the search were ("Atrial Fibrillation"), ("Ablation, Catheter"), AND (Agent, Anti-Arrhythmia). There were no restrictions on language or year of publication. Additionally, all relevant study reference lists and review articles included in other potentially eligible clinical trials were manually searched. Eligibility Criteria All studies included had to meet the following requirements: Phase 2 or Phase 3 randomized controlled trials evaluating patients older than 18 who were diagnosed with atrial fibrillation (paroxysmal or persistent) and were allocated to catheter ablation (cryoablation or radiofrequency) as an intervention or antiarrhythmic agents for the treatment of the arrhythmia. Randomized clinical trials that included patients with an implanted cardiac defibrillator, post hoc analyses of a randomized clinical trial, conference abstracts, systematic reviews, narrative reviews, case report series, and letters to the editor were excluded. Outcomes The primary outcomes considered were the recurrence of any atrial tachyarrhythmia (presence of atrial fibrillation, atrial flutter, or atrial tachycardia of 30 seconds or more duration after the 90-day blanking period, measured in frequencies and relative risk) and the proportion of patients free of recurrence (number of patients without any atrial tachyarrhythmia after 24 months of randomization, measured in frequencies and relative risk). Secondary outcomes included serious adverse events (e.g., cardiac tamponade, hematomas, venous stenosis, major hemorrhagic complications, perimyocarditis, stroke, TIA, death, measured through frequencies with relative risks), catheter ablation reintervention rate (patients requiring a second or third catheter ablation procedure after the blanking period), improvement of LVEF or functional capacity (VO2 max, NYHA functional class, measured in frequencies with relative risk), procedure-related complications (any reported complication from catheter ablation), and side effects of antiarrhythmic drugs (any reported reaction caused by antiarrhythmic drug administration at any dose). Data Extraction The results were compressed into a library after the electronic search for studies based on the search strategies. EndNote 21 was used to eliminate duplicates. Subsequently, the screening phase was carried out independently and blindly by evaluating titles and abstracts, applying each article’s inclusion and exclusion criteria. This phase was conducted using the Rayyan platform. The studies included in this phase were analyzed in their full text. A second screening process was conducted to confirm the inclusion and exclusion criteria. Finally, the included studies were added to the systematic review, and data extraction began. In cases of disagreement, a third reviewing author was consulted. A previously prepared form was used in Excel for data extraction. Data extraction for each study was conducted individually and masked. The Excel data table included the following variables: authors, year of publication, country, type of study, number of participants per intervention and control arm, selection criteria, description of the intervention and control, and primary and secondary outcomes. Risk of Bias Assessment The risk of bias (RoB) was independently assessed using the RoB 2.0 tool. Disagreements were resolved through discussion with a third author (JJB). RoB for each domain and study was described as low, with some concerns, or high for RCTs. Data Synthesis Random-effects models with the inverse variance method were used for all meta-analyses of the effects of catheter ablation (cryoballoon or radiofrequency) compared to antiarrhythmic therapy (amiodarone, propafenone, beta-blockers, flecainide, among others) on primary and secondary outcomes. The Paule-Mandel method was used to calculate the tau² variance between studies. The effects of catheter ablation compared to drug therapy on dichotomous outcomes were described with relative risks (RR) and their 95% confidence intervals (CI). The continuity correction method made adjustments for null events in one or two arms of the RCT. If more than five studies were found for the meta-analysis, the Hartung-Knapp method was applied for adjustments. Statistical heterogeneity among RCTs was described by the I² statistic, with values categorized as low ( 60%) levels of heterogeneity. For sensitivity analysis, fixed effects and the Mantel-Haenszel method were used. The metabin function of the R 3.5.1 meta-library ( www.r-project.org ) was employed. Publication bias was assessed using a funnel plot and Egger’s test. GRADE Assessment The GRADE methodology was used to assess the evidence’s certainty and the intervention’s degree of recommendation for all outcomes. GRADE was based on its domains, including the risk of bias, inconsistency, indirectness, imprecision, and publication bias. The certainty of the evidence was determined by the outcome and described in the summary of results (SoF) tables, which were created using the online software GRADEpro GDT. RESULTS Selection of studies After the search, 2270 studies were found, of which 638 were duplicates. Of the remaining 1632 studies, a total of 1587 studies were excluded by title and abstract. Of the remaining 45 evaluated in full text, 15 randomized controlled trials were included (Fig. 1 ) ( 11 – 25 ). Characteristics of included studies The systematic review included 15 randomized controlled trials (RCTs) conducted across various countries and regions, including North America, Europe, Asia, and South America. The trials investigated the comparative efficacy and safety of catheter ablation versus antiarrhythmic drug therapy in patients with atrial fibrillation (AF). Study populations varied, with follow-up durations ranging from 9 to 60 months and sample sizes between 60 and 648 participants. The mean age of participants ranged from 49.7 to 72.1 years, with studies addressing paroxysmal, persistent, and long-standing persistent AF. Most studies enrolled both male and female participants, with a predominance of males in several trials. Catheter ablation techniques included cryoballoon ablation and radiofrequency ablation, utilizing advanced mapping systems and procedural modifications as required by the study protocols. The antiarrhythmic drugs evaluated included amiodarone, sotalol, propafenone, dronedarone, and flecainide, among others, administered either as first-line therapy or after prior treatment failure. The primary outcomes assessed across the studies included the recurrence of AF and atrial tachyarrhythmias, freedom from AF at long-term follow-up, and the delay in disease progression. Secondary outcomes encompassed serious adverse events, procedure-related adverse events, improvement in left ventricular ejection fraction (LVEF), functional capacity (NYHA classification), symptomatic relief, mortality, and reintervention rates. Several studies also evaluated safety outcomes, such as stroke, transient ischemic attacks, and other thromboembolic events. Notably, the trials employed rigorous methodologies, including randomization, allocation concealment, and blinded outcome assessments, although the level of reporting varied among studies. Clinical trial registration numbers were provided for most studies, ensuring transparency and adherence to international ethical standards. The heterogeneity in study designs, populations, and outcome definitions underscores the importance of synthesizing these findings to comprehensively evaluate the comparative benefits and risks of catheter ablation versus antiarrhythmic drugs in AF management (Table 1 ). Table 1 Characteristics of included studies Study Identification Country or Region Clinical Trial Registration Follow-Up Duration (Months) Sample Size (Ablation vs Drugs) Type of AF Mean Age ablation Mean Age control Primary Outcomes Andrade JG et al. (2021) Canada NCT02825979 12 154 vs 149 Paroxysmal and persistent 57.7 59.5 Recurrence of atrial tachyarrhythmia Ding J et al. (2022) China NR 36 102 vs 102 Paroxysmal 60.9 60.7 Persistent atrial tachyarrhythmia occurrence Jaïs P et al. (2008) North America and Europe NCT00540787 12 53 vs 59 Paroxysmal 49.7 52.4 AF-free rate Kuck KH et al. (2021) Austria, Germany, etc. NCT01570361 36 128 vs 127 Paroxysmal 67.8 67.6 Persistent AF/AT occurrence Kunnis et al. (2021) Argentina, Australia, etc. NCT01803438 12 107 vs 111 Paroxysmal 50.5 54.1 AA recurrence Martins L et al. (2024) Brazil NCT04023461 24 30 vs 30 Paroxysmal 71.1 72.1 AF/AT recurrence Mont Ll et al. (2014) Spain NCT00863213 12 98 vs 48 Persistent 55 55 AF/flutter recurrence Morillo et al. (2014) Canada, Germany, Czech Republic, etc NCT00392054 24 66 vs 61 Paroxysmal 56.3 54.3 AA recurrence Nielsen et al. (2012) Denmark, Finland, Sweden NCT00133211 24 146 vs 148 Paroxysmal 56 54 AF burden Pappone C et al. (2006) Italy NCT00340314 12 99 vs 99 Paroxysmal 55 57 Freedom from AT Wazni O et al. (2005) Italy and Germany NR 12 33 vs 37 Paroxysmal and persistent 53 54 AF recurrence Forleo G et al. (2009) Not Reported NR 12 35 vs 35 Paroxysmal and persistent 63.2 64.8 AF recurrence Wazni O et al. (2021) USA NCT03118518 12 104 vs 99 Paroxysmal 60.4 61.6 Treatment success Wilber D et al. (2010) USA, Europe, Canada NCT00116428 9 106 vs 61 Paroxysmal 55.5 56.1 Treatment success Wu G et al. (2021) China NCT01341353 60 327 vs 321 Persistent 64.8 64.6 Morbidity Table 2 GRADE summary of findings Outcome Relative effect (RR) [95% CI] Risk with AAD (per 1,000) Risk with ablation (per 1,000) Absolute difference (per 1,000) Participants (studies) Risk of bias Inconsistency Indirectness Imprecision Publication bias Certainty (GRADE) Comments Recurrence of any atrial tachyarrhythmia (≥ 90d blanking) 0.57 [0.51; 0.63] 673.3 383.8 -289.5 2127 ( 9 ) serious not serious not serious not serious undetected Moderate Effect consistent with low heterogeneity (I²=9%); downgraded for risk of bias (open-label, cross-over, selective reporting). Freedom from recurrence at 24 months 1.59 [0.94; 2.69] 416.1 661.6 245.5 1129 ( 4 ) serious serious not serious serious undetected Very low Very high heterogeneity (I²=92%) and wide CI crossing no effect; small number of studies. Progression to persistent atrial fibrillation 0.14 [0.08; 0.25] 142.9 20.0 -122.9 519 ( 3 ) serious not serious not serious serious undetected Moderate Sparse events; prediction interval wide; downgraded for risk of bias and imprecision. Serious adverse events 0.91 [0.72; 1.15] 124.7 113.5 -11.2 1559 ( 7 ) serious not serious not serious serious undetected Low CI includes appreciable harm and benefit; downgraded for imprecision and risk of bias. Reintervention after initial treatment (repeat procedure) 24.72 [11.47; 53.26] Not applicable Observed risk ~ 195.2 Not comparable 1458 ( 7 ) serious not serious very serious serious undetected Very low Outcome not conceptually applicable to the AAD arm (zero events); continuity corrections; indirectness and imprecision. Side effects attributable to antiarrhythmic drugs 0.04 [0.01; 0.10] 104.1 4.2 -99.9 4031 ( 9 ) serious not serious not serious not serious undetected Moderate Events occurred almost exclusively in the AAD arm; effect precise and consistent; downgraded for risk of bias. Procedure-related complications (ablation) 8.52 [3.12; 23.27] 3.5 29.8 26.3 4626 ( 11 ) serious serious not serious serious undetected Low Moderate heterogeneity (I²=54%) and wide CI; absolute risks remain low; downgraded for risk of bias, inconsistency and imprecision. Risk of bias assessment Risk of bias was evaluated with the RoB 2 tool for the nine randomized trials contributing data to the primary outcome (recurrence of any atrial tachyarrhythmia; Fig. 2 ). Overall risk of bias was judged low in one trial, of some concern in two trials, and high in six trials. At the domain level, concerns most frequently arose from deviations from the intended interventions (five trials at high risk and one with some concerns), largely reflecting open-label designs with cross-over or protocol deviations that could differentially affect recurrence ascertainment. The randomization process was generally adequate but incompletely reported (seven trials with some concerns and two at low risk), mainly due to missing details on allocation concealment or baseline imbalances. Missing outcome data were uncommon (seven trials at low risk), although two trials were rated high risk because of attrition or incomplete rhythm follow-up that could bias recurrence estimates. Measurement of the outcome was consistently judged low risk across all trials, as recurrence was defined a priori and captured through objective electrocardiographic monitoring. Selective reporting contributed additional limitations (five trials at high risk and two with some concerns), driven by the absence of prespecified analytic plans or multiplicity of follow-up windows and definitions. Taken together, while detection bias is unlikely to account for the observed treatment effects, the predominance of high risk in domains related to intervention implementation and selective reporting warrants caution regarding the magnitude of benefit and justifies downgrading the certainty of evidence for risk of bias in GRADE (Fig. 2 ). Effect of Catheter ablation on outcomes The meta-analysis in Fig. 3 evaluates the recurrence of atrial arrhythmia in patients with atrial fibrillation treated with catheter ablation compared to antiarrhythmic drug therapy. A total of nine randomized controlled trials were included, encompassing 1,120 patients in the catheter ablation group and 1,007 in the control group. The results demonstrate a significant reduction in the recurrence of atrial arrhythmia among patients undergoing catheter ablation, with a pooled relative risk (RR) of 0.57 (95% CI: 0.51–0.63; CoE Moderate), indicating a 43% lower risk of arrhythmia recurrence compared to pharmacological therapy. The heterogeneity across studies was low (I² = 9%, p = 0.36), suggesting high consistency among the included trials. The studies by Wu et al. (2021) and Kuck et al. (2021) contributed the highest weights in the analysis, with RR values of 0.50 and 0.58, respectively, both favoring catheter ablation. The prediction interval (0.50–0.64) reinforces these findings’ robustness and applicability to future studies. Furthermore, the observed variability in Fig. 4 underscores the importance of considering patient-specific factors when evaluating the long-term efficacy of catheter ablation. While the pooled estimate suggests a favorable trend towards ablation, the confidence interval crosses unity (RR: 1.59, 95% CI: 0.94–2.69; CoE: Low), indicating that the overall effect remains inconclusive. The significant heterogeneity (I² = 92%) suggests that differences in study protocols, operator expertise, and patient characteristics likely contribute to outcome discrepancies. Notably, the study by Wu et al. (2021) demonstrated the most substantial benefit (RR: 2.43, 95% CI: 2.02–2.92), whereas Martins et al. (2024) reported a more modest effect (RR: 1.33, 95% CI: 0.95–1.88), emphasizing the need for individualized treatment approaches. The wide prediction interval (0.37–6.84) suggests that future studies may report a broad range of effect sizes, reinforcing the necessity for further high-quality randomized trials to clarify the durability of ablation benefits. Similarly, Fig. 5 reinforces the potential benefit of catheter ablation in preventing disease progression, as evidenced by a substantial reduction in the risk of progression to persistent atrial fibrillation. The meta-analysis of three randomized controlled trials, including 519 patients, demonstrated a pooled relative risk of 0.14 (95% CI: 0.08–0.25; CoE: Moderate), indicating an 86% reduction in the risk of atrial fibrillation progression in patients undergoing catheter ablation compared to antiarrhythmic drug therapy. Notably, the studies by Ding et al. (2022) and Kuck et al. (2021) yielded consistent results with relative risks of 0.12 (95% CI: 0.03–0.50) and 0.13 (95% CI: 0.03–0.57), respectively, both favoring ablation. However, Martins et al. (2024) reported a higher RR of 0.20 (95% CI: 0.02–1.61), with a confidence interval crossing unity, suggesting a less definitive benefit. Importantly, heterogeneity was negligible (I² = 0%, p = 0.92), indicating a high level of consistency across studies and strengthening the reliability of the findings. While wide, the prediction interval (0.00–52.73) suggests that future studies are likely to confirm a significant protective effect of ablation in preventing disease progression. Building upon the findings regarding efficacy, Fig. 6 evaluates the occurrence of serious adverse events in patients undergoing catheter ablation compared to antiarrhythmic drug therapy. The meta-analysis, which includes seven randomized controlled trials with a total of 1,559 patients, demonstrates a pooled relative risk of 0.91 (95% CI: 0.72–1.15; CoE: Moderate), suggesting no statistically significant difference in the rate of serious adverse events between both treatment strategies. The individual study estimates show variability, with some studies, such as Kunnis et al. (2021), reporting a lower risk of adverse events with ablation (RR: 0.73, 95% CI: 0.48–1.12), whereas Morillo et al. (2014) found a higher risk (RR: 1.85, 95% CI: 0.48–7.07), though with wide confidence intervals. Importantly, heterogeneity across studies was negligible (I² = 0%, p = 0.79), indicating high consistency in the results and strengthening the reliability of the pooled estimate. The prediction interval (0.64–1.28) suggests that future studies are unlikely to yield substantially different conclusions. Expanding on the safety considerations, Fig. 7 evaluates reintervention rates following catheter ablation compared to antiarrhythmic drug therapy. The meta-analysis of seven randomized controlled trials, comprising 1,458 patients, reveals a significantly higher likelihood of requiring reintervention in the catheter ablation group, with a pooled relative risk of 24.72 (95% CI: 11.47–53.26; CoE: Moderate). This result underscores the procedural nature of ablation, where some patients may require additional interventions due to arrhythmia recurrence or incomplete initial success. Notably, the study by Pappone et al. (2006) reported the highest RR (140.90, 95% CI: 8.81–2253.90), highlighting a potential variability in reintervention rates across different settings and techniques. Conversely, studies such as Morillo et al. (2014) reported a lower, yet still elevated, RR (8.37, 95% CI: 0.49–142.04). Despite these variations, the overall heterogeneity was negligible (I² = 0%, p = 0.90), suggesting consistency across trial findings. The wide prediction interval (7.13–85.66) indicates that future studies may observe a range of effect sizes but are unlikely to contradict the conclusion that reintervention is substantially more common in patients undergoing catheter ablation. In contrast to the increased reintervention rates observed with catheter ablation, Fig. 8 highlights a significant advantage of this approach regarding safety, particularly regarding the adverse effects of antiarrhythmic drug therapy. The meta-analysis, which includes nine randomized controlled trials with a total of 4,031 patients, demonstrates a markedly lower risk of side effects in the catheter ablation group, with a pooled relative risk of 0.04 (95% CI: 0.01–0.10; CoE: High). This finding indicates a 96% reduction in the likelihood of experiencing adverse drug reactions among patients treated with catheter ablation compared to those receiving antiarrhythmic drugs. Notably, studies such as Packer et al. (2019) and Pappone et al. (2011) reported the most potent protective effects (RR: 0.01, 95% CI: 0.00–0.18, and RR: 0.01, 95% CI: 0.00–0.12, respectively), reinforcing the consistent benefit of ablation in reducing drug-related complications. Importantly, heterogeneity across studies was negligible (I² = 0%, p = 0.66), reflecting a high level of agreement among the included trials. The prediction interval (0.01–0.11) suggests that future studies are unlikely to yield substantially different conclusions. These results further support the role of catheter ablation as a safer long-term strategy by minimizing the burden of pharmacological side effects, which can often lead to poor adherence and treatment discontinuation in patients with atrial fibrillation. In contrast to the reduced risk of adverse effects associated with antiarrhythmic drugs, Fig. 9 highlights the increased risk of complications directly related to the catheter ablation procedure. The meta-analysis, which includes 11 randomized controlled trials with a total of 4,626 patients, demonstrates a significantly higher rate of procedure-related complications in the ablation group, with a pooled relative risk of 8.52 (95% CI: 3.12–23.27; CoE: Moderate). This finding indicates that patients undergoing catheter ablation are over eight times more likely to experience procedural complications compared to those receiving antiarrhythmic drug therapy. Notably, studies such as Packer et al. (2019) reported an exceptionally high RR (138.25, 95% CI: 8.51–2246.53), while other trials, such as Martins et al. (2024), showed a lower RR (0.50, 95% CI: 0.14–1.82), reflecting variability in procedural risk across different settings. The heterogeneity of the analysis was moderate (I² = 54%, p = 0.01), suggesting differences in complication rates depending on factors such as operator expertise, ablation techniques, and patient characteristics. The wide prediction interval (0.89–81.67) indicates that future studies may report varying degrees of risk but are unlikely to refute the overall finding of increased procedural complications ultimately. GRADE assessment Using GRADE, the certainty of evidence was judged moderate for two key benefits of catheter ablation, low for two safety outcomes, and very low for outcomes with severe indirectness or imprecision. For the primary outcome—recurrence of any atrial tachyarrhythmia after a 90-day blanking period (9 trials; n = 2,127)—catheter ablation probably reduces recurrence compared with antiarrhythmic drug therapy (RR 0.57, 95% CI 0.51–0.63; moderate certainty). Based on an average control risk of 673 per 1,000, ablation corresponds to about 384 per 1,000 with recurrence, an absolute reduction of ~ 290 fewer per 1,000. Certainty was downgraded for risk of bias (open-label designs, cross-over, and selective reporting), but inconsistency, indirectness, and imprecision were not serious. For freedom from recurrence at 24 months (4 trials; n = 1,129), the direction of effect favored ablation (RR 1.59, 95% CI 0.94–2.69), but the estimate was very imprecise and highly heterogeneous (I²≈92%). Using a control risk of 416 per 1,000 free of recurrence, ablation could increase this to ~ 662 per 1,000 (+ 246 per 1,000), although the true effect is very uncertain; overall certainty was rated very low due to serious risk of bias, serious inconsistency, and serious imprecision For progression to persistent atrial fibrillation (3 trials; n = 519), ablation probably reduces progression (RR 0.14, 95% CI 0.08–0.25; moderate certainty). With a control risk of 143 per 1,000, the corresponding risk with ablation is ~ 20 per 1,000, an absolute reduction of ~ 123 per 1,000. The rating was downgraded for risk of bias and imprecision given sparse events, while inconsistency and indirectness were not serious. For serious adverse events (7 trials; n = 1,559), there may be little to no difference between strategies (RR 0.91, 95% CI 0.72–1.15; low certainty). Against a control risk of 125 per 1,000, ablation corresponds to ~ 114 per 1,000 (11 fewer per 1,000), but the confidence interval includes both appreciable benefit and harm; certainty was downgraded for risk of bias and imprecision. Drug-related side effects occurred almost exclusively in the antiarrhythmic arm. Across 9 trials (n = 4,031), ablation probably results in far fewer drug-related adverse effects (RR 0.04, 95% CI 0.01–0.10; moderate certainty). Given a control risk of 104 per 1,000, the risk with ablation is ~ 4 per 1,000, an absolute reduction of ~ 100 per 1,000. We downgraded for risk of bias but not for inconsistency, indirectness, or imprecision. Procedure-related complications were uncommon but more frequent with ablation (11 trials; n = 4,626). The pooled relative effect suggested an increase in complications with ablation (RR 8.52, 95% CI 3.12–23.27; low certainty). With a control risk of ~ 3.5 per 1,000, the corresponding risk with ablation is ~ 29.8 per 1,000, an absolute increase of ~ 26 per 1,000. Certainty was downgraded for risk of bias, inconsistency, and imprecision, reflecting low event rates, moderate heterogeneity, and wide confidence intervals. Reintervention (repeat procedure) was reported only in the ablation arm (7 trials; n = 1,458), yielding a large relative estimate driven by continuity corrections (RR 24.72, 95% CI 11.47–53.26). Because this outcome is not conceptually applicable to the antiarrhythmic-drug comparator, and event counts were sparse, the evidence was rated very low certainty due to very serious indirectness and serious imprecision; a comparative absolute effect is not meaningful. Taken together, moderate-certainty evidence indicates that catheter ablation probably reduces arrhythmia recurrence and progression compared with antiarrhythmic drugs, with no clear difference in serious adverse events. However, ablation may increase procedure-related complications (low certainty), and the need for reintervention cannot be reliably compared across strategies (very low certainty). These findings support the clinical benefit of ablation for rhythm control while underscoring procedural risks and the limitations of the available randomized evidence. DISCUSSION This meta-analysis provides robust evidence supporting the efficacy of catheter ablation compared to antiarrhythmic drug (AAD) therapy in patients with atrial fibrillation (AF). The results demonstrate that catheter ablation significantly reduces atrial arrhythmia recurrence (RR: 0.57; 95% CI: 0.44–0.73) and prevents progression to persistent AF (RR: 0.12; 95% CI: 0.06–0.24), while showing comparable rates of serious adverse events (RR: 1.00; 95% CI: 0.84–1.19). However, ablation was associated with an increased likelihood of reintervention (RR: 36.04; 95% CI: 16.10–80.65) and procedural complications (RR: 8.52; 95% CI: 3.12–23.27). These findings reinforce the role of catheter ablation as a disease-modifying strategy in managing AF, particularly in patients who fail to respond to or cannot tolerate AADs. The findings of this meta-analysis align with the results of prior large-scale randomized controlled trials (RCTs) and meta-analyses. For instance, Kheshti et al. (2024) reported a 53% reduction in AF recurrence (RR: 0.47; 95% CI: 0.36–0.61) and an 89% reduction in AF progression (RR: 0.11; 95% CI: 0.02–0.65) among patients undergoing catheter ablation compared to AAD therapy. This remarkable efficacy highlights the advantage of ablation as a rhythm control strategy over pharmacological treatment. Moreover, their study demonstrated an improvement in left ventricular ejection fraction (LVEF) by a mean difference (MD) of 6.84%, consistent with the findings of Zhang et al. (2024), which revealed significant improvements in LVEF and quality of life metrics in patients with AF and heart failure (HF) undergoing ablation ( 25 ). In contrast, some studies have highlighted the challenges associated with catheter ablation. The DECAAF II trial, which explored sex-specific differences, showed that female patients had worse outcomes, including higher recurrence rates (53.3% vs. 40.2%, p < 0.01) and lower quality of life improvements post-ablation compared to males. These findings underscore the need for personalized approaches, particularly in patient subgroups with differing baseline characteristics or comorbidities ( 26 ). The study by Rujirachun et al. (2025) also provided insights into the impact of rheumatoid arthritis (RA) on ablation outcomes, revealing a higher risk of recurrence among RA patients (RR: 1.59; 95% CI: 1.10–2.29). This suggests systemic inflammatory conditions may influence ablation success, warranting further research into optimizing outcomes in these populations ( 27 ). The significant reduction in recurrence and progression rates observed in this meta-analysis can be attributed to catheter ablation’s superior ability to achieve and maintain sinus rhythm by targeting the electrophysiological mechanisms underlying AF. Pulmonary vein isolation (PVI), the cornerstone of ablation, effectively interrupts arrhythmogenic foci, which AADs do not address adequately. Additionally, advancements in ablation techniques, such as high-density mapping and contact force sensing, have improved procedural efficacy and safety ( 28 ). However, the increased risk of reintervention and procedural complications associated with ablation is a critical consideration. Complications such as cardiac tamponade, vascular injury, and pulmonary vein stenosis remain concerns despite procedural advancements. These risks highlight the need for careful patient selection and procedural standardization. Studies like Zhang et al. (2024) have emphasized that the safety profile of ablation is comparable to that of medical therapy when performed by experienced operators ( 29 ). Interestingly, the comparable rates of serious adverse events between ablation and AAD therapy (RR: 1.00; 95% CI: 0.84–1.19) suggest that the long-term benefits of rhythm control offset procedural risks. Furthermore, the significantly lower incidence of side effects in the ablation group compared to AAD therapy (RR: 0.04; 95% CI: 0.01–0.10) highlights a significant advantage of ablation, particularly for patients intolerant to AAD-related adverse effects ( 30 ). Limitations The strengths of this meta-analysis include its rigorous methodology, adherence to PRISMA guidelines, and inclusion of high-quality RCTs with large sample sizes. The use of random-effects models ensures robust estimates despite heterogeneity among studies. However, several limitations warrant consideration. High heterogeneity in some outcomes, such as recurrence rates (I² = 83.8%), reflects variability in patient populations, ablation protocols, and follow-up durations. Additionally, the exclusion of non-English studies may introduce publication bias. The lack of uniformity in reporting procedural complications and reintervention criteria across studies further limits comparability. Conclusion This meta-analysis demonstrates that catheter ablation is a highly effective strategy for managing AF, offering significant reductions in arrhythmia recurrence and disease progression with comparable safety to AAD therapy. However, the increased risk of reintervention and procedural complications underscores the importance of individualized patient selection and shared decision-making. These findings reinforce the role of catheter ablation as a cornerstone of AF management and provide a strong foundation for future research to optimize its use in diverse patient populations. Declarations Funding/Support: This research did not receive a specific grant from any public, commercial, or not-for-profit funding agency. Financial disclosures: No financial disclosures Clinical trial number: Not applicable CRediT authorship contribution statement. Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing—original draft, Writing—review & editing, Visualization, Supervision, Project administration: J.J.B., F.D.P., C.D.S., M.S.A., M.J.A., J.M.M., A.H.L., O.R.-L. Guarantor: J.J.B. Corresponding author: J.J.B. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work. References Lip, G., Fauchier, L., Freedman, S., Gelder, I., Natale, A., Gianni, C., Nattel, S., Potpara, T., Rienstra, M., Tse, H., & Lane, D. (2016). Atrial fibrillation. Nature Reviews Disease Primers, 2. https://doi.org/10.1038/nrdp.2016.16. Wijesurendra, R., & Casadei, B. (2019). 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Ablation versus medical therapy for patients with atrial fibrillation: An updated meta-analysis. CLIN CARDIOL. 2024;47(2). doi:10.1002/clc.24184. Younes H, Sohns C, Akoum N, Feng H, Tsakiris E, Hajjar AHE, et al. Sex-specific outcomes and left atrial remodeling following catheter ablation of persistent atrial fibrillation: results from the DECAAF II trial. J Interv Card Electrophysiol. 2024;67(8):1843-50. doi:10.1007/s10840-024-01831-w. Rujirachun P, Wattanachayakul P, Taveeamornrat S, Ungprasert P, Tokavanich N, Jongnarangsin K. Atrial Fibrillation Recurrence Risk After Catheter Ablation in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Clin Cardiol. 2025;48(1):e70021. doi:10.1002/clc.70021. Ang R, Domenichini G, Finlay MC, Schilling RJ, Hunter RJ. The Hot and the Cold: Radiofrequency Versus Cryoballoon Ablation for Atrial Fibrillation. Curr Cardiol Rep. 2015;17(9). doi:10.1007/s11886-015-0631-7. Zhang Z, Letsas KP, Zhang N, Efremidis M, Xu G, Li G, et al. Linear Ablation Following Pulmonary Vein Isolation in Patients with Atrial Fibrillation: A Meta-Analysis. PACE Pacing Clin Electrophysiol. 2016;39(6):623-30. doi:10.1111/pace.12841 . Supplementary Files Supplementaltable.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 10 Dec, 2025 Reviewers invited by journal 10 Dec, 2025 Editor assigned by journal 30 Nov, 2025 First submitted to journal 09 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7820043","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":558410813,"identity":"d2796f27-93e7-4c02-a3c9-654c8fd9543f","order_by":0,"name":"Joshuan J. 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16:51:03","extension":"png","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":43981,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/4c4d9dd4456c4ed945afbca9.png"},{"id":98249949,"identity":"7c0e0974-6eb4-44ef-91b6-9a543c268c9a","added_by":"auto","created_at":"2025-12-15 16:44:58","extension":"png","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":56708,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/ed9e01dcfcb0d8dc0e4aba13.png"},{"id":98249943,"identity":"1c0dab3f-5025-41fe-a2b7-ca69ad223332","added_by":"auto","created_at":"2025-12-15 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16:44:57","extension":"png","order_by":30,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":57953,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure5.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/64144452d9ce8d4a79246752.png"},{"id":98433774,"identity":"64940dde-9456-4f66-903e-68f643bb36e4","added_by":"auto","created_at":"2025-12-17 16:51:06","extension":"png","order_by":31,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":79694,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure6.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/01b6aff233b7f4ea87e67f69.png"},{"id":98249950,"identity":"a2a5f9ee-fb52-44fd-b1f3-04d9edbda08b","added_by":"auto","created_at":"2025-12-15 16:44:58","extension":"png","order_by":32,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":87257,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure7.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/4f1a24462bacf350994e60ac.png"},{"id":98249948,"identity":"d011a7f8-0bb3-4f84-94bf-2e3b03015879","added_by":"auto","created_at":"2025-12-15 16:44:58","extension":"png","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":90381,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure8.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/be4ef558d17be70c2d4addb5.png"},{"id":98434953,"identity":"25cb16e7-b4f4-4033-81fd-f3f49b8d6ba7","added_by":"auto","created_at":"2025-12-17 16:52:49","extension":"png","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":113178,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure9.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/160b9206ae4952acf6d221a3.png"},{"id":98249951,"identity":"fcef83ca-1220-4231-be7b-e4339f76ca4a","added_by":"auto","created_at":"2025-12-15 16:44:58","extension":"xml","order_by":35,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":134085,"visible":true,"origin":"","legend":"","description":"","filename":"SYSRD25013760structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/9c36fb2cba49e5ac0b1df759.xml"},{"id":98249953,"identity":"75dd919d-cf27-4118-b306-4110e7bd1562","added_by":"auto","created_at":"2025-12-15 16:44:58","extension":"html","order_by":36,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":149257,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/39b34b408c01d9ac9ba71cdd.html"},{"id":98249908,"identity":"dddaf39f-6dce-4e9a-b991-6c2bcd5526e8","added_by":"auto","created_at":"2025-12-15 16:44:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":140659,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA 2020 flow diagram.\u003c/strong\u003e Identification, screening, eligibility and inclusion of studies comparing catheter ablation versus antiarrhythmic drug therapy (AAD). After removing 638 duplicates, 1,632 records were screened; 45 full texts were assessed for eligibility; 15 randomized controlled trials were included in the review. Abbreviations: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/ef2bc338a50b185084e9a702.png"},{"id":98249911,"identity":"ace67404-fa7e-468a-b883-3055e595affd","added_by":"auto","created_at":"2025-12-15 16:44:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":97564,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRisk of bias (RoB 2) traffic-light plot for the primary outcome.\u003c/strong\u003e Domain-level judgments and overall risk of bias for each included randomized trial reporting recurrence of any atrial tachyarrhythmia. Domains: D1 randomization process; D2 deviations from intended interventions; D3 missing outcome data; D4 measurement of the outcome; D5 selection of the reported result. Colors denote low risk (green), some concerns (yellow), and high risk (red).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/388824283407be8e6fefb3d1.png"},{"id":98434937,"identity":"ee57cdb1-82bc-4658-b056-4a6c366b0c3c","added_by":"auto","created_at":"2025-12-17 16:52:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":372447,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRecurrence of any atrial tachyarrhythmia after a 90-day blanking period.\u003c/strong\u003e Individual and pooled risk ratios comparing catheter ablation versus AAD therapy. Random-effects meta-analysis (Paule–Mandel τ², Hartung–Knapp adjustment) shows a lower risk of recurrence with ablation (summary RR 0.57, 95% CI 0.51–0.63; I²=9%; prediction interval 0.50–0.64). Abbreviations: RR, risk ratio; CI, confidence interval; I², inconsistency; τ², between-study variance.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/b71b5ae2bc8da6bd8ae29f07.png"},{"id":98433107,"identity":"333f01a2-de37-4b2a-a3a8-338bd729f13b","added_by":"auto","created_at":"2025-12-17 16:50:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":264808,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFreedom from atrial tachyarrhythmia at 24 months.\u003c/strong\u003e Individual and pooled risk ratios for the proportion of patients without recurrence at two years. Random-effects model (Paule–Mandel τ², Hartung–Knapp) suggests a direction favoring ablation but with very high heterogeneity (summary RR 1.59, 95% CI 0.94–2.69; I²=92%; prediction interval 0.37–6.84). Interpretation should consider substantial between-study variability. Abbreviations as above.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/13f81df225a78c806a840ff6.png"},{"id":98249914,"identity":"f555b970-ea70-4bb9-b310-33ab9b56f341","added_by":"auto","created_at":"2025-12-15 16:44:57","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":230118,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProgression to persistent atrial fibrillation.\u003c/strong\u003e Individual and pooled risk ratios comparing ablation versus AAD therapy. Random-effects model (Paule–Mandel τ², Hartung–Knapp) indicates lower progression with ablation (summary RR 0.14, 95% CI 0.08–0.25; I²=0%). The very wide prediction interval reflects sparse data across few studies. Abbreviations as above.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/cffa3d3f582be5fa5777bf12.png"},{"id":98433098,"identity":"19b0dbfc-c473-42f9-8d74-14805083e843","added_by":"auto","created_at":"2025-12-17 16:50:15","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":323325,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSerious adverse events (SAE).\u003c/strong\u003e Individual and pooled risk ratios for SAE during follow-up. Random-effects meta-analysis (Paule–Mandel τ², Hartung–Knapp) shows no clear difference between ablation and AAD therapy (summary RR 0.91, 95% CI 0.72–1.15; I²=0%). Abbreviations: SAE, serious adverse events.\u003c/p\u003e","description":"","filename":"Figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/41697d60a92945ef52de27e6.png"},{"id":98434855,"identity":"503ddc55-722a-4952-833c-7339a77bfb40","added_by":"auto","created_at":"2025-12-17 16:52:41","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":359351,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReintervention after initial treatment assignment.\u003c/strong\u003e Individual and pooled risk ratios for repeat procedures. Events occurred only in the ablation arm; a continuity correction was applied to studies with zero events in the control arm. The random-effects model (Paule–Mandel τ², Hartung–Knapp) yields a high relative estimate (summary RR 24.72, 95% CI 11.47–53.26; I²=0%). This comparison should be interpreted cautiously because “reintervention” is not conceptually applicable to the AAD arm. Abbreviations as above.\u003c/p\u003e","description":"","filename":"Figure7.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/1ecab2df9c9c6412d0fd14c2.png"},{"id":98249920,"identity":"e4f2e949-40e7-42ff-84dc-73349639e009","added_by":"auto","created_at":"2025-12-15 16:44:57","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":382320,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSide effects attributable to antiarrhythmic drugs.\u003c/strong\u003e Individual and pooled risk ratios for AAD-related adverse effects. Events occurred only in the AAD arm; a continuity correction was applied to studies with zero events in the ablation arm. Random-effects model (Paule–Mandel τ², Hartung–Knapp) shows markedly fewer drug-related side effects in the ablation group (summary RR 0.04, 95% CI 0.01–0.10; I²=0%). Abbreviations as above.\u003c/p\u003e","description":"","filename":"Figure8.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/387faafe68b040b49cc91e10.png"},{"id":98434455,"identity":"4b32a934-ae30-46c8-a059-04f06fc07778","added_by":"auto","created_at":"2025-12-17 16:52:08","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":471365,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProcedure-related complications.\u003c/strong\u003e Individual and pooled risk ratios for complications directly related to the ablation procedure versus control. Random-effects model (Paule–Mandel τ², Hartung–Knapp) indicates a higher risk with ablation (summary RR 8.52, 95% CI 3.12–23.27; I²=54%; prediction interval 0.89–81.67). Results reflect low absolute event rates but a consistent relative increase associated with the invasive procedure. Abbreviations as above.\u003c/p\u003e","description":"","filename":"Figure9.png","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/fd7d4a56366f41ac2247b441.png"},{"id":98445144,"identity":"5f6dc3b3-8b72-4b3d-b97b-06f0c0188f43","added_by":"auto","created_at":"2025-12-17 17:19:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3739692,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/e4179f0e-d58b-4bf1-a280-f38ed66d44ae.pdf"},{"id":98249933,"identity":"9e1c0f68-3dc4-468b-ace4-5185e4a7a00e","added_by":"auto","created_at":"2025-12-15 16:44:57","extension":"docx","order_by":15,"title":"","display":"","copyAsset":false,"role":"supplement","size":27113,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaltable.docx","url":"https://assets-eu.researchsquare.com/files/rs-7820043/v1/4ab08176cdd1c7ecbc4d0e48.docx"}],"financialInterests":"","formattedTitle":"Catheter Ablation vs Antiarrhythmic Agents in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAtrial fibrillation (AF), as the most frequent sustained cardiac dysrhythmia in the adult population, is characterized by rapid and disorganized atrial activation, which, if not diagnosed in time, can lead to serious complications such as stroke and heart failure, including death (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Its prevalence is increasing, affecting millions of adults, and the various clinical complications affect the quality of life not only at the personal level, but also at the family and social levels (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOver the years, multiple management strategies have been developed for this type of supraventricular arrhythmia, including pharmacological therapy and surgical interventions such as catheter ablation, which offer both benefits and risks for the health of sufferers (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, the choice between pharmacological therapy vs. catheter ablation therapy is under discussion, because for years, pharmacological therapy has been the first management option before considering ablation (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite this, in recent years several randomized clinical trials have been carried out, which directly compare pharmacological therapy vs catheter ablation, demonstrating that the latter generates a reduction in the recurrence of arrhythmias, thus improving the quality of life of individuals, providing greater cost/benefit with a lower rate of adverse events and a lower rate of treatment abandonment (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt should be noted that it is not only about controlling the disease and its recurrences, but also about generating impact on the quality of life, how a pharmacological strategy vs. ablation affects the reduction of the burden of atrial fibrillation, as well as to see how it impacts on other comorbidities, if these improve or worsen with the implementation of specific management (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Therefore, atrial fibrillation negatively affects the quality of life of the population, also shortening their years of life, so the option of rhythm control vs. heart rate control can generate a reduction in the burden of atrial fibrillation, and thus improve the quality of life (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe present systematic review and meta-analysis aim to analyze the most updated and contrasted evidence on the efficacy and safety of catheter ablation compared to antiarrhythmic therapy (different drugs will be analyzed: beta-blockers, amiodarone, propafenone, among others) in patients with Atrial Fibrillation. Studies such as clinical trials and systematic reviews with meta-analysis are included to provide a detailed analysis of the advantages and limitations of each therapeutic strategy, as well as the evaluation of changes in quality of life, adverse side effects, and mortality cases.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis study was a systematic review with meta-analysis. The reference elements for systematic reviews and meta-analyses (PRISMA-2020) informed this review. This protocol was registered in PROSPERO database (CRD42025635074).\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eSearches\u003c/h2\u003e\n \u003cp\u003eThis research used PubMed, Scopus, the Web of Science, and Embase databases. The searches were carried out starting September 29, 2024. Keywords, MeSH terms (PubMed), and Entree thesaurus terms (Scopus, Embase) were included in this review.\u003c/p\u003e\n \u003cp\u003eSubsequently, a search strategy was applied to each database (Supplemental Table\u0026nbsp;1). The primary phrases used in the search were (\u0026quot;Atrial Fibrillation\u0026quot;), (\u0026quot;Ablation, Catheter\u0026quot;), AND (Agent, Anti-Arrhythmia). There were no restrictions on language or year of publication. Additionally, all relevant study reference lists and review articles included in other potentially eligible clinical trials were manually searched.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eAll studies included had to meet the following requirements: Phase 2 or Phase 3 randomized controlled trials evaluating patients older than 18 who were diagnosed with atrial fibrillation (paroxysmal or persistent) and were allocated to catheter ablation (cryoablation or radiofrequency) as an intervention or antiarrhythmic agents for the treatment of the arrhythmia.\u003c/p\u003e\n\u003cp\u003eRandomized clinical trials that included patients with an implanted cardiac defibrillator, post hoc analyses of a randomized clinical trial, conference abstracts, systematic reviews, narrative reviews, case report series, and letters to the editor were excluded.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcomes considered were the recurrence of any atrial tachyarrhythmia (presence of atrial fibrillation, atrial flutter, or atrial tachycardia of 30 seconds or more duration after the 90-day blanking period, measured in frequencies and relative risk) and the proportion of patients free of recurrence (number of patients without any atrial tachyarrhythmia after 24 months of randomization, measured in frequencies and relative risk).\u003c/p\u003e\n\u003cp\u003eSecondary outcomes included serious adverse events (e.g., cardiac tamponade, hematomas, venous stenosis, major hemorrhagic complications, perimyocarditis, stroke, TIA, death, measured through frequencies with relative risks), catheter ablation reintervention rate (patients requiring a second or third catheter ablation procedure after the blanking period), improvement of LVEF or functional capacity (VO2 max, NYHA functional class, measured in frequencies with relative risk), procedure-related complications (any reported complication from catheter ablation), and side effects of antiarrhythmic drugs (any reported reaction caused by antiarrhythmic drug administration at any dose).\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eThe results were compressed into a library after the electronic search for studies based on the search strategies. EndNote 21 was used to eliminate duplicates. Subsequently, the screening phase was carried out independently and blindly by evaluating titles and abstracts, applying each article\u0026rsquo;s inclusion and exclusion criteria. This phase was conducted using the Rayyan platform.\u003c/p\u003e\n\u003cp\u003eThe studies included in this phase were analyzed in their full text. A second screening process was conducted to confirm the inclusion and exclusion criteria. Finally, the included studies were added to the systematic review, and data extraction began. In cases of disagreement, a third reviewing author was consulted.\u003c/p\u003e\n\u003cp\u003eA previously prepared form was used in Excel for data extraction. Data extraction for each study was conducted individually and masked. The Excel data table included the following variables: authors, year of publication, country, type of study, number of participants per intervention and control arm, selection criteria, description of the intervention and control, and primary and secondary outcomes.\u003c/p\u003e\n\u003ch3\u003eRisk of Bias Assessment\u003c/h3\u003e\n\u003cp\u003eThe risk of bias (RoB) was independently assessed using the RoB 2.0 tool. Disagreements were resolved through discussion with a third author (JJB). RoB for each domain and study was described as low, with some concerns, or high for RCTs.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eData Synthesis\u003c/h2\u003e\n \u003cp\u003eRandom-effects models with the inverse variance method were used for all meta-analyses of the effects of catheter ablation (cryoballoon or radiofrequency) compared to antiarrhythmic therapy (amiodarone, propafenone, beta-blockers, flecainide, among others) on primary and secondary outcomes. The Paule-Mandel method was used to calculate the tau\u0026sup2; variance between studies. The effects of catheter ablation compared to drug therapy on dichotomous outcomes were described with relative risks (RR) and their 95% confidence intervals (CI). The continuity correction method made adjustments for null events in one or two arms of the RCT. If more than five studies were found for the meta-analysis, the Hartung-Knapp method was applied for adjustments. Statistical heterogeneity among RCTs was described by the I\u0026sup2; statistic, with values categorized as low (\u0026lt;\u0026thinsp;30%), moderate (30\u0026ndash;60%), or high (\u0026gt;\u0026thinsp;60%) levels of heterogeneity. For sensitivity analysis, fixed effects and the Mantel-Haenszel method were used. The metabin function of the R 3.5.1 meta-library (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.r-project.org\u003c/span\u003e\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e)\u003c/span\u003e was employed. Publication bias was assessed using a funnel plot and Egger\u0026rsquo;s test.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eGRADE Assessment\u003c/h3\u003e\n\u003cp\u003eThe GRADE methodology was used to assess the evidence\u0026rsquo;s certainty and the intervention\u0026rsquo;s degree of recommendation for all outcomes. GRADE was based on its domains, including the risk of bias, inconsistency, indirectness, imprecision, and publication bias. The certainty of the evidence was determined by the outcome and described in the summary of results (SoF) tables, which were created using the online software GRADEpro GDT.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSelection of studies\u003c/h2\u003e \u003cp\u003eAfter the search, 2270 studies were found, of which 638 were duplicates. Of the remaining 1632 studies, a total of 1587 studies were excluded by title and abstract. Of the remaining 45 evaluated in full text, 15 randomized controlled trials were included (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) (\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of included studies\u003c/h2\u003e \u003cp\u003eThe systematic review included 15 randomized controlled trials (RCTs) conducted across various countries and regions, including North America, Europe, Asia, and South America. The trials investigated the comparative efficacy and safety of catheter ablation versus antiarrhythmic drug therapy in patients with atrial fibrillation (AF). Study populations varied, with follow-up durations ranging from 9 to 60 months and sample sizes between 60 and 648 participants. The mean age of participants ranged from 49.7 to 72.1 years, with studies addressing paroxysmal, persistent, and long-standing persistent AF. Most studies enrolled both male and female participants, with a predominance of males in several trials. Catheter ablation techniques included cryoballoon ablation and radiofrequency ablation, utilizing advanced mapping systems and procedural modifications as required by the study protocols. The antiarrhythmic drugs evaluated included amiodarone, sotalol, propafenone, dronedarone, and flecainide, among others, administered either as first-line therapy or after prior treatment failure.\u003c/p\u003e \u003cp\u003eThe primary outcomes assessed across the studies included the recurrence of AF and atrial tachyarrhythmias, freedom from AF at long-term follow-up, and the delay in disease progression. Secondary outcomes encompassed serious adverse events, procedure-related adverse events, improvement in left ventricular ejection fraction (LVEF), functional capacity (NYHA classification), symptomatic relief, mortality, and reintervention rates. Several studies also evaluated safety outcomes, such as stroke, transient ischemic attacks, and other thromboembolic events. Notably, the trials employed rigorous methodologies, including randomization, allocation concealment, and blinded outcome assessments, although the level of reporting varied among studies. Clinical trial registration numbers were provided for most studies, ensuring transparency and adherence to international ethical standards. The heterogeneity in study designs, populations, and outcome definitions underscores the importance of synthesizing these findings to comprehensively evaluate the comparative benefits and risks of catheter ablation versus antiarrhythmic drugs in AF management (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy Identification\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCountry or Region\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical Trial Registration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFollow-Up Duration (Months)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSample Size (Ablation vs Drugs)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eType of AF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean Age\u003c/p\u003e \u003cp\u003eablation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMean Age control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePrimary Outcomes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAndrade JG et al. (2021)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT02825979\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e154 vs 149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal and persistent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e57.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e59.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eRecurrence of atrial tachyarrhythmia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDing J et al. (2022)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102 vs 102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e60.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePersistent atrial tachyarrhythmia occurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJa\u0026iuml;s P et al. (2008)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNorth America and Europe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT00540787\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53 vs 59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e49.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e52.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAF-free rate\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKuck KH et al. (2021)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAustria, Germany, etc.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT01570361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e128 vs 127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e67.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e67.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePersistent AF/AT occurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKunnis et al. (2021)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArgentina, Australia, etc.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT01803438\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e107 vs 111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e54.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAA recurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMartins L et al. (2024)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrazil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT04023461\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 vs 30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e71.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e72.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAF/AT recurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMont Ll et al. (2014)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT00863213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e98 vs 48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePersistent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAF/flutter recurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMorillo et al. (2014)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCanada, Germany, Czech Republic, etc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT00392054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66 vs 61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e54.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAA recurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNielsen et al. (2012)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDenmark, Finland, Sweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT00133211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e146 vs 148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAF burden\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePappone C et al. (2006)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT00340314\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e99 vs 99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFreedom from AT\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWazni O et al. (2005)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItaly and Germany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 vs 37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal and persistent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAF recurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eForleo G et al. (2009)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot Reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35 vs 35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal and persistent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eAF recurrence\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWazni O et al. (2021)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT03118518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e104 vs 99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e61.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTreatment success\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWilber D et al. (2010)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUSA, Europe, Canada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT00116428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e106 vs 61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParoxysmal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTreatment success\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWu G et al. (2021)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNCT01341353\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e327 vs 321\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePersistent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMorbidity\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGRADE summary of findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRelative effect (RR) [95% CI]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRisk with AAD (per 1,000)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRisk with ablation (per 1,000)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAbsolute difference (per 1,000)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eParticipants (studies)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRisk of bias\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eInconsistency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eIndirectness\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eImprecision\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePublication bias\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eCertainty (GRADE)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eComments\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRecurrence of any atrial tachyarrhythmia (\u0026ge;\u0026thinsp;90d blanking)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.57 [0.51; 0.63]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e673.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e383.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-289.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2127 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eundetected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eEffect consistent with low heterogeneity (I\u0026sup2;=9%); downgraded for risk of bias (open-label, cross-over, selective reporting).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFreedom from recurrence at 24 months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.59 [0.94; 2.69]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e416.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e661.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e245.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1129 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eundetected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVery low\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eVery high heterogeneity (I\u0026sup2;=92%) and wide CI crossing no effect; small number of studies.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProgression to persistent atrial fibrillation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.14 [0.08; 0.25]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-122.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e519 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eundetected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eSparse events; prediction interval wide; downgraded for risk of bias and imprecision.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSerious adverse events\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.91 [0.72; 1.15]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e113.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-11.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1559 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eundetected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCI includes appreciable harm and benefit; downgraded for imprecision and risk of bias.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReintervention after initial treatment (repeat procedure)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24.72 [11.47; 53.26]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eObserved risk\u0026thinsp;~\u0026thinsp;195.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNot comparable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1458 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003every serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eundetected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVery low\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eOutcome not conceptually applicable to the AAD arm (zero events); continuity corrections; indirectness and imprecision.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSide effects attributable to antiarrhythmic drugs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.04 [0.01; 0.10]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-99.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4031 (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eundetected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eEvents occurred almost exclusively in the AAD arm; effect precise and consistent; downgraded for risk of bias.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProcedure-related complications (ablation)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.52 [3.12; 23.27]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4626 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003enot serious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eserious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eundetected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eModerate heterogeneity (I\u0026sup2;=54%) and wide CI; absolute risks remain low; downgraded for risk of bias, inconsistency and imprecision.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias assessment\u003c/h2\u003e \u003cp\u003eRisk of bias was evaluated with the RoB 2 tool for the nine randomized trials contributing data to the primary outcome (recurrence of any atrial tachyarrhythmia; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Overall risk of bias was judged low in one trial, of some concern in two trials, and high in six trials. At the domain level, concerns most frequently arose from deviations from the intended interventions (five trials at high risk and one with some concerns), largely reflecting open-label designs with cross-over or protocol deviations that could differentially affect recurrence ascertainment. The randomization process was generally adequate but incompletely reported (seven trials with some concerns and two at low risk), mainly due to missing details on allocation concealment or baseline imbalances. Missing outcome data were uncommon (seven trials at low risk), although two trials were rated high risk because of attrition or incomplete rhythm follow-up that could bias recurrence estimates. Measurement of the outcome was consistently judged low risk across all trials, as recurrence was defined a priori and captured through objective electrocardiographic monitoring. Selective reporting contributed additional limitations (five trials at high risk and two with some concerns), driven by the absence of prespecified analytic plans or multiplicity of follow-up windows and definitions. Taken together, while detection bias is unlikely to account for the observed treatment effects, the predominance of high risk in domains related to intervention implementation and selective reporting warrants caution regarding the magnitude of benefit and justifies downgrading the certainty of evidence for risk of bias in GRADE (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eEffect of Catheter ablation on outcomes\u003c/h2\u003e \u003cp\u003eThe meta-analysis in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e evaluates the recurrence of atrial arrhythmia in patients with atrial fibrillation treated with catheter ablation compared to antiarrhythmic drug therapy. A total of nine randomized controlled trials were included, encompassing 1,120 patients in the catheter ablation group and 1,007 in the control group. The results demonstrate a significant reduction in the recurrence of atrial arrhythmia among patients undergoing catheter ablation, with a pooled relative risk (RR) of 0.57 (95% CI: 0.51\u0026ndash;0.63; CoE Moderate), indicating a 43% lower risk of arrhythmia recurrence compared to pharmacological therapy. The heterogeneity across studies was low (I\u0026sup2; = 9%, p\u0026thinsp;=\u0026thinsp;0.36), suggesting high consistency among the included trials. The studies by Wu et al. (2021) and Kuck et al. (2021) contributed the highest weights in the analysis, with RR values of 0.50 and 0.58, respectively, both favoring catheter ablation. The prediction interval (0.50\u0026ndash;0.64) reinforces these findings\u0026rsquo; robustness and applicability to future studies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFurthermore, the observed variability in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e underscores the importance of considering patient-specific factors when evaluating the long-term efficacy of catheter ablation. While the pooled estimate suggests a favorable trend towards ablation, the confidence interval crosses unity (RR: 1.59, 95% CI: 0.94\u0026ndash;2.69; CoE: Low), indicating that the overall effect remains inconclusive. The significant heterogeneity (I\u0026sup2; = 92%) suggests that differences in study protocols, operator expertise, and patient characteristics likely contribute to outcome discrepancies. Notably, the study by Wu et al. (2021) demonstrated the most substantial benefit (RR: 2.43, 95% CI: 2.02\u0026ndash;2.92), whereas Martins et al. (2024) reported a more modest effect (RR: 1.33, 95% CI: 0.95\u0026ndash;1.88), emphasizing the need for individualized treatment approaches. The wide prediction interval (0.37\u0026ndash;6.84) suggests that future studies may report a broad range of effect sizes, reinforcing the necessity for further high-quality randomized trials to clarify the durability of ablation benefits.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSimilarly, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e reinforces the potential benefit of catheter ablation in preventing disease progression, as evidenced by a substantial reduction in the risk of progression to persistent atrial fibrillation. The meta-analysis of three randomized controlled trials, including 519 patients, demonstrated a pooled relative risk of 0.14 (95% CI: 0.08\u0026ndash;0.25; CoE: Moderate), indicating an 86% reduction in the risk of atrial fibrillation progression in patients undergoing catheter ablation compared to antiarrhythmic drug therapy. Notably, the studies by Ding et al. (2022) and Kuck et al. (2021) yielded consistent results with relative risks of 0.12 (95% CI: 0.03\u0026ndash;0.50) and 0.13 (95% CI: 0.03\u0026ndash;0.57), respectively, both favoring ablation. However, Martins et al. (2024) reported a higher RR of 0.20 (95% CI: 0.02\u0026ndash;1.61), with a confidence interval crossing unity, suggesting a less definitive benefit. Importantly, heterogeneity was negligible (I\u0026sup2; = 0%, p\u0026thinsp;=\u0026thinsp;0.92), indicating a high level of consistency across studies and strengthening the reliability of the findings. While wide, the prediction interval (0.00\u0026ndash;52.73) suggests that future studies are likely to confirm a significant protective effect of ablation in preventing disease progression.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBuilding upon the findings regarding efficacy, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e evaluates the occurrence of serious adverse events in patients undergoing catheter ablation compared to antiarrhythmic drug therapy. The meta-analysis, which includes seven randomized controlled trials with a total of 1,559 patients, demonstrates a pooled relative risk of 0.91 (95% CI: 0.72\u0026ndash;1.15; CoE: Moderate), suggesting no statistically significant difference in the rate of serious adverse events between both treatment strategies. The individual study estimates show variability, with some studies, such as Kunnis et al. (2021), reporting a lower risk of adverse events with ablation (RR: 0.73, 95% CI: 0.48\u0026ndash;1.12), whereas Morillo et al. (2014) found a higher risk (RR: 1.85, 95% CI: 0.48\u0026ndash;7.07), though with wide confidence intervals. Importantly, heterogeneity across studies was negligible (I\u0026sup2; = 0%, p\u0026thinsp;=\u0026thinsp;0.79), indicating high consistency in the results and strengthening the reliability of the pooled estimate. The prediction interval (0.64\u0026ndash;1.28) suggests that future studies are unlikely to yield substantially different conclusions.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eExpanding on the safety considerations, Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e evaluates reintervention rates following catheter ablation compared to antiarrhythmic drug therapy. The meta-analysis of seven randomized controlled trials, comprising 1,458 patients, reveals a significantly higher likelihood of requiring reintervention in the catheter ablation group, with a pooled relative risk of 24.72 (95% CI: 11.47\u0026ndash;53.26; CoE: Moderate). This result underscores the procedural nature of ablation, where some patients may require additional interventions due to arrhythmia recurrence or incomplete initial success. Notably, the study by Pappone et al. (2006) reported the highest RR (140.90, 95% CI: 8.81\u0026ndash;2253.90), highlighting a potential variability in reintervention rates across different settings and techniques. Conversely, studies such as Morillo et al. (2014) reported a lower, yet still elevated, RR (8.37, 95% CI: 0.49\u0026ndash;142.04). Despite these variations, the overall heterogeneity was negligible (I\u0026sup2; = 0%, p\u0026thinsp;=\u0026thinsp;0.90), suggesting consistency across trial findings. The wide prediction interval (7.13\u0026ndash;85.66) indicates that future studies may observe a range of effect sizes but are unlikely to contradict the conclusion that reintervention is substantially more common in patients undergoing catheter ablation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn contrast to the increased reintervention rates observed with catheter ablation, Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e highlights a significant advantage of this approach regarding safety, particularly regarding the adverse effects of antiarrhythmic drug therapy. The meta-analysis, which includes nine randomized controlled trials with a total of 4,031 patients, demonstrates a markedly lower risk of side effects in the catheter ablation group, with a pooled relative risk of 0.04 (95% CI: 0.01\u0026ndash;0.10; CoE: High). This finding indicates a 96% reduction in the likelihood of experiencing adverse drug reactions among patients treated with catheter ablation compared to those receiving antiarrhythmic drugs. Notably, studies such as Packer et al. (2019) and Pappone et al. (2011) reported the most potent protective effects (RR: 0.01, 95% CI: 0.00\u0026ndash;0.18, and RR: 0.01, 95% CI: 0.00\u0026ndash;0.12, respectively), reinforcing the consistent benefit of ablation in reducing drug-related complications. Importantly, heterogeneity across studies was negligible (I\u0026sup2; = 0%, p\u0026thinsp;=\u0026thinsp;0.66), reflecting a high level of agreement among the included trials. The prediction interval (0.01\u0026ndash;0.11) suggests that future studies are unlikely to yield substantially different conclusions. These results further support the role of catheter ablation as a safer long-term strategy by minimizing the burden of pharmacological side effects, which can often lead to poor adherence and treatment discontinuation in patients with atrial fibrillation.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn contrast to the reduced risk of adverse effects associated with antiarrhythmic drugs, Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e highlights the increased risk of complications directly related to the catheter ablation procedure. The meta-analysis, which includes 11 randomized controlled trials with a total of 4,626 patients, demonstrates a significantly higher rate of procedure-related complications in the ablation group, with a pooled relative risk of 8.52 (95% CI: 3.12\u0026ndash;23.27; CoE: Moderate). This finding indicates that patients undergoing catheter ablation are over eight times more likely to experience procedural complications compared to those receiving antiarrhythmic drug therapy. Notably, studies such as Packer et al. (2019) reported an exceptionally high RR (138.25, 95% CI: 8.51\u0026ndash;2246.53), while other trials, such as Martins et al. (2024), showed a lower RR (0.50, 95% CI: 0.14\u0026ndash;1.82), reflecting variability in procedural risk across different settings. The heterogeneity of the analysis was moderate (I\u0026sup2; = 54%, p\u0026thinsp;=\u0026thinsp;0.01), suggesting differences in complication rates depending on factors such as operator expertise, ablation techniques, and patient characteristics. The wide prediction interval (0.89\u0026ndash;81.67) indicates that future studies may report varying degrees of risk but are unlikely to refute the overall finding of increased procedural complications ultimately.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eGRADE assessment\u003c/h2\u003e \u003cp\u003eUsing GRADE, the certainty of evidence was judged moderate for two key benefits of catheter ablation, low for two safety outcomes, and very low for outcomes with severe indirectness or imprecision. For the primary outcome\u0026mdash;recurrence of any atrial tachyarrhythmia after a 90-day blanking period (9 trials; n\u0026thinsp;=\u0026thinsp;2,127)\u0026mdash;catheter ablation probably reduces recurrence compared with antiarrhythmic drug therapy (RR 0.57, 95% CI 0.51\u0026ndash;0.63; moderate certainty). Based on an average control risk of 673 per 1,000, ablation corresponds to about 384 per 1,000 with recurrence, an absolute reduction of ~\u0026thinsp;290 fewer per 1,000. Certainty was downgraded for risk of bias (open-label designs, cross-over, and selective reporting), but inconsistency, indirectness, and imprecision were not serious.\u003c/p\u003e \u003cp\u003eFor freedom from recurrence at 24 months (4 trials; n\u0026thinsp;=\u0026thinsp;1,129), the direction of effect favored ablation (RR 1.59, 95% CI 0.94\u0026ndash;2.69), but the estimate was very imprecise and highly heterogeneous (I\u0026sup2;\u0026asymp;92%). Using a control risk of 416 per 1,000 free of recurrence, ablation could increase this to ~\u0026thinsp;662 per 1,000 (+\u0026thinsp;246 per 1,000), although the true effect is very uncertain; overall certainty was rated very low due to serious risk of bias, serious inconsistency, and serious imprecision\u003c/p\u003e \u003cp\u003eFor progression to persistent atrial fibrillation (3 trials; n\u0026thinsp;=\u0026thinsp;519), ablation probably reduces progression (RR 0.14, 95% CI 0.08\u0026ndash;0.25; moderate certainty). With a control risk of 143 per 1,000, the corresponding risk with ablation is ~\u0026thinsp;20 per 1,000, an absolute reduction of ~\u0026thinsp;123 per 1,000. The rating was downgraded for risk of bias and imprecision given sparse events, while inconsistency and indirectness were not serious.\u003c/p\u003e \u003cp\u003eFor serious adverse events (7 trials; n\u0026thinsp;=\u0026thinsp;1,559), there may be little to no difference between strategies (RR 0.91, 95% CI 0.72\u0026ndash;1.15; low certainty). Against a control risk of 125 per 1,000, ablation corresponds to ~\u0026thinsp;114 per 1,000 (11 fewer per 1,000), but the confidence interval includes both appreciable benefit and harm; certainty was downgraded for risk of bias and imprecision.\u003c/p\u003e \u003cp\u003eDrug-related side effects occurred almost exclusively in the antiarrhythmic arm. Across 9 trials (n\u0026thinsp;=\u0026thinsp;4,031), ablation probably results in far fewer drug-related adverse effects (RR 0.04, 95% CI 0.01\u0026ndash;0.10; moderate certainty). Given a control risk of 104 per 1,000, the risk with ablation is ~\u0026thinsp;4 per 1,000, an absolute reduction of ~\u0026thinsp;100 per 1,000. We downgraded for risk of bias but not for inconsistency, indirectness, or imprecision.\u003c/p\u003e \u003cp\u003eProcedure-related complications were uncommon but more frequent with ablation (11 trials; n\u0026thinsp;=\u0026thinsp;4,626). The pooled relative effect suggested an increase in complications with ablation (RR 8.52, 95% CI 3.12\u0026ndash;23.27; low certainty). With a control risk of ~\u0026thinsp;3.5 per 1,000, the corresponding risk with ablation is ~\u0026thinsp;29.8 per 1,000, an absolute increase of ~\u0026thinsp;26 per 1,000. Certainty was downgraded for risk of bias, inconsistency, and imprecision, reflecting low event rates, moderate heterogeneity, and wide confidence intervals.\u003c/p\u003e \u003cp\u003eReintervention (repeat procedure) was reported only in the ablation arm (7 trials; n\u0026thinsp;=\u0026thinsp;1,458), yielding a large relative estimate driven by continuity corrections (RR 24.72, 95% CI 11.47\u0026ndash;53.26). Because this outcome is not conceptually applicable to the antiarrhythmic-drug comparator, and event counts were sparse, the evidence was rated very low certainty due to very serious indirectness and serious imprecision; a comparative absolute effect is not meaningful.\u003c/p\u003e \u003cp\u003eTaken together, moderate-certainty evidence indicates that catheter ablation probably reduces arrhythmia recurrence and progression compared with antiarrhythmic drugs, with no clear difference in serious adverse events. However, ablation may increase procedure-related complications (low certainty), and the need for reintervention cannot be reliably compared across strategies (very low certainty). These findings support the clinical benefit of ablation for rhythm control while underscoring procedural risks and the limitations of the available randomized evidence.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis meta-analysis provides robust evidence supporting the efficacy of catheter ablation compared to antiarrhythmic drug (AAD) therapy in patients with atrial fibrillation (AF). The results demonstrate that catheter ablation significantly reduces atrial arrhythmia recurrence (RR: 0.57; 95% CI: 0.44\u0026ndash;0.73) and prevents progression to persistent AF (RR: 0.12; 95% CI: 0.06\u0026ndash;0.24), while showing comparable rates of serious adverse events (RR: 1.00; 95% CI: 0.84\u0026ndash;1.19). However, ablation was associated with an increased likelihood of reintervention (RR: 36.04; 95% CI: 16.10\u0026ndash;80.65) and procedural complications (RR: 8.52; 95% CI: 3.12\u0026ndash;23.27). These findings reinforce the role of catheter ablation as a disease-modifying strategy in managing AF, particularly in patients who fail to respond to or cannot tolerate AADs.\u003c/p\u003e \u003cp\u003eThe findings of this meta-analysis align with the results of prior large-scale randomized controlled trials (RCTs) and meta-analyses. For instance, Kheshti et al. (2024) reported a 53% reduction in AF recurrence (RR: 0.47; 95% CI: 0.36\u0026ndash;0.61) and an 89% reduction in AF progression (RR: 0.11; 95% CI: 0.02\u0026ndash;0.65) among patients undergoing catheter ablation compared to AAD therapy. This remarkable efficacy highlights the advantage of ablation as a rhythm control strategy over pharmacological treatment. Moreover, their study demonstrated an improvement in left ventricular ejection fraction (LVEF) by a mean difference (MD) of 6.84%, consistent with the findings of Zhang et al. (2024), which revealed significant improvements in LVEF and quality of life metrics in patients with AF and heart failure (HF) undergoing ablation (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn contrast, some studies have highlighted the challenges associated with catheter ablation. The DECAAF II trial, which explored sex-specific differences, showed that female patients had worse outcomes, including higher recurrence rates (53.3% vs. 40.2%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and lower quality of life improvements post-ablation compared to males. These findings underscore the need for personalized approaches, particularly in patient subgroups with differing baseline characteristics or comorbidities (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe study by Rujirachun et al. (2025) also provided insights into the impact of rheumatoid arthritis (RA) on ablation outcomes, revealing a higher risk of recurrence among RA patients (RR: 1.59; 95% CI: 1.10\u0026ndash;2.29). This suggests systemic inflammatory conditions may influence ablation success, warranting further research into optimizing outcomes in these populations (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). The significant reduction in recurrence and progression rates observed in this meta-analysis can be attributed to catheter ablation\u0026rsquo;s superior ability to achieve and maintain sinus rhythm by targeting the electrophysiological mechanisms underlying AF. Pulmonary vein isolation (PVI), the cornerstone of ablation, effectively interrupts arrhythmogenic foci, which AADs do not address adequately. Additionally, advancements in ablation techniques, such as high-density mapping and contact force sensing, have improved procedural efficacy and safety (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, the increased risk of reintervention and procedural complications associated with ablation is a critical consideration. Complications such as cardiac tamponade, vascular injury, and pulmonary vein stenosis remain concerns despite procedural advancements. These risks highlight the need for careful patient selection and procedural standardization. Studies like Zhang et al. (2024) have emphasized that the safety profile of ablation is comparable to that of medical therapy when performed by experienced operators (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eInterestingly, the comparable rates of serious adverse events between ablation and AAD therapy (RR: 1.00; 95% CI: 0.84\u0026ndash;1.19) suggest that the long-term benefits of rhythm control offset procedural risks. Furthermore, the significantly lower incidence of side effects in the ablation group compared to AAD therapy (RR: 0.04; 95% CI: 0.01\u0026ndash;0.10) highlights a significant advantage of ablation, particularly for patients intolerant to AAD-related adverse effects (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLimitations\u003c/p\u003e \u003cp\u003e The strengths of this meta-analysis include its rigorous methodology, adherence to PRISMA guidelines, and inclusion of high-quality RCTs with large sample sizes. The use of random-effects models ensures robust estimates despite heterogeneity among studies. However, several limitations warrant consideration. High heterogeneity in some outcomes, such as recurrence rates (I\u0026sup2; = 83.8%), reflects variability in patient populations, ablation protocols, and follow-up durations. Additionally, the exclusion of non-English studies may introduce publication bias. The lack of uniformity in reporting procedural complications and reintervention criteria across studies further limits comparability.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis meta-analysis demonstrates that catheter ablation is a highly effective strategy for managing AF, offering significant reductions in arrhythmia recurrence and disease progression with comparable safety to AAD therapy. However, the increased risk of reintervention and procedural complications underscores the importance of individualized patient selection and shared decision-making. These findings reinforce the role of catheter ablation as a cornerstone of AF management and provide a strong foundation for future research to optimize its use in diverse patient populations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding/Support:\u0026nbsp;\u003c/strong\u003eThis research did not receive a specific grant from any public,\u0026nbsp;commercial, or not-for-profit funding agency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosures:\u0026nbsp;\u003c/strong\u003eNo financial disclosures\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement.\u003c/strong\u003e Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing\u0026mdash;original draft, Writing\u0026mdash;review \u0026amp; editing, Visualization, Supervision, Project administration: J.J.B., F.D.P., C.D.S., M.S.A., M.J.A., J.M.M., A.H.L., O.R.-L. Guarantor: J.J.B. Corresponding author: J.J.B. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLip, G., Fauchier, L., Freedman, S., Gelder, I., Natale, A., Gianni, C., Nattel, S., Potpara, T., Rienstra, M., Tse, H., \u0026amp; Lane, D. (2016). Atrial fibrillation. Nature Reviews Disease Primers, 2. https://doi.org/10.1038/nrdp.2016.16.\u003c/li\u003e\n\u003cli\u003eWijesurendra, R., \u0026amp; Casadei, B. (2019). Mechanisms of atrial fibrillation. Heart, 105, 1860 - 1867. https://doi.org/10.1136/heartjnl-2018-314267.\u003c/li\u003e\n\u003cli\u003eKornej, J., B\u0026ouml;rschel, C., Benjamin, E., \u0026amp; Schnabel, R. (2020). Epidemiology of Atrial Fibrillation in the 21st Century. 127, 20 - 4. https://doi.org/10.1161/CIRCRESAHA.120.316340.\u003c/li\u003e\n\u003cli\u003eRavens, U. (2010). Antiarrhythmic therapy in atrial fibrillation.. Pharmacology \u0026amp; therapeutics, 128 1, 129-45. https://doi.org/10.1016/j.pharmthera.2010.06.004.\u003c/li\u003e\n\u003cli\u003eGanz, L., \u0026amp; Antman, E. (1997). Antiarrhythmic Drug Therapy in the Management of Atrial Fibrillation. Journal of Cardiovascular Electrophysiology, 8. https://doi.org/10.1111/j.1540-8167.1997.tb01005.x.\u003c/li\u003e\n\u003cli\u003eTuragam, M., Musikantow, D., Whang, W., Koruth, J., Miller, M., Langan, M., Sofi, A., Choudry, S., Dukkipati, S., \u0026amp; Reddy, V. (2021). Assessment of Catheter Ablation or Antiarrhythmic Drugs for First-line Therapy of Atrial Fibrillation: A Meta-analysis of Randomized Clinical Trials.. JAMA cardiology. https://doi.org/10.1001/jamacardio.2021.0852.\u003c/li\u003e\n\u003cli\u003eStabile, G., Bertaglia, E., Senatore, G., De Simone, A., Zoppo, F., Donnici, G., Turco, P., Pascotto, P., Fazzari, M., \u0026amp; Vitale, D. (2006). Catheter ablation treatment in patients with drug-refractory atrial fibrillation: a prospective, multi-centre, randomized, controlled study (Catheter Ablation For The Cure Of Atrial Fibrillation Study).. European heart journal, 27 2, 216-21 . https://doi.org/10.1093/EURHEARTJ/EHI583.\u003c/li\u003e\n\u003cli\u003eSamuel, M., Khairy, P., Champagne, J., Deyell, M., Macle, L., Leong‐Sit, P., Novak, P., Badra-Verdu, M., Sapp, J., Tardif, J., \u0026amp; Andrade, J. (2021). Association of Atrial Fibrillation Burden With Health-Related Quality of Life After Atrial Fibrillation Ablation: Substudy of the Cryoballoon vs Contact-Force Atrial Fibrillation Ablation (CIRCA-DOSE) Randomized Clinical Trial.. JAMA cardiology. https://doi.org/10.1001/jamacardio.2021.3063.\u003c/li\u003e\n\u003cli\u003eJenkins, L., Brodsky, M., Schron, E., Chung, M., Rocco, T., Lader, E., Constantine, M., Sheppard, R., Holmes, D., Mateski, D., Floden, L., Prasun, M., Greene, H., \u0026amp; Shemanski, L. (2005). Quality of life in atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.. American heart journal, 149 1, 112-20 . https://doi.org/10.1016/J.AHJ.2004.03.065.\u003c/li\u003e\n\u003cli\u003eThrall, G., Lane, D., Carroll, D., \u0026amp; Lip, G. (2006). Quality of life in patients with atrial fibrillation: a systematic review.. The American journal of medicine, 119 5, 448.e1-19 . https://doi.org/10.1016/J.AMJMED.2005.10.057.\u003c/li\u003e\n\u003cli\u003eAndrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, et al. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. N Engl J Med. 2021;384(4):305-15. doi:10.1056/NEJMoa2029980.\u003c/li\u003e\n\u003cli\u003eDing J, Cheng A, Li P, Yan Y, Shi Y, Xue Z, et al. Cryoballoon catheter ablation or drug therapy to delay progression of atrial fibrillation: A single-center randomized trial. Front Cardiovasc Med. 2022;9. doi:10.3389/fcvm.2022.1003305.\u003c/li\u003e\n\u003cli\u003eJa\u0026iuml;s P, Cauchemez B, Macle L, Daoud E, Khairy P, Subbiah R, et al. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation: the A4 study. Circulation. 2008;118(24):2498-505. doi:10.1161/circulationaha.108.772582.\u003c/li\u003e\n\u003cli\u003eKuck KH, Lebedev DS, Mikhaylov EN, Romanov A, Gell\u0026eacute;r L, Kalējs O, et al. Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST). Europace. 2021;23(3):362-9. doi:10.1093/europace/euaa298.\u003c/li\u003e\n\u003cli\u003eKuniss M, Pavlovic N, Velagic V, Hermida JS, Healey S, Arena G, et al. Cryoballoon ablation vs. antiarrhythmic drugs: First-line therapy for patients with paroxysmal atrial fibrillation. Europace. 2021;23(7):1033-41. doi:10.1093/europace/euab029.\u003c/li\u003e\n\u003cli\u003eMartins LCB, Pisani CF, Dorfman FK, Darrieux FCC, Wu TC, Ferraz AP, et al. Randomized Study Comparing Radiofrequency Ablation with the PVAC Gold System vs. Antiarrhythmic Drugs in Elderly Patients with Symptomatic Atrial Fibrillation. Arq Bras Cardiol. 2024;121(6). doi:10.36660/abc.20230684.\u003c/li\u003e\n\u003cli\u003eMont L, Bisbal F, Hern\u0026aacute;ndez-Madrid A, P\u0026eacute;rez-Castellano N, Vi\u0026ntilde;olas X, Arenal A, et al. Catheter ablation vs. antiarrhythmic drug treatment of persistent atrial fibrillation: a multicentre, randomized, controlled trial (SARA study). Eur Heart J. 2014;35(8):501-7. doi:10.1093/eurheartj/eht457.\u003c/li\u003e\n\u003cli\u003eMorillo CA, Verma A, Connolly SJ, Kuck KH, Nair GM, Champagne J, et al. Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation (RAAFT-2) A Randomized Trial. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. 2014;311(7):692-9. doi:10.1001/jama.2014.467.\u003c/li\u003e\n\u003cli\u003eNielsen JC, Johannessen A, Raatikainen P, Hindricks G, Walfridsson H, Kongstad O, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. New England Journal of Medicine. 2012;367(17):1587-95. doi:10.1056/NEJMoa1113566.\u003c/li\u003e\n\u003cli\u003ePappone C, Augello G, Sala S, Gugliotta F, Vicedomini G, Gulletta S, et al. A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll Cardiol. 2006;48(11):2340-7. doi:10.1016/j.jacc.2006.08.037.\u003c/li\u003e\n\u003cli\u003eWazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. Jama. 2005;293(21):2634-40. doi:10.1001/jama.293.21.2634.\u003c/li\u003e\n\u003cli\u003eForleo GB, Mantica M, De Luca L, Leo R, Santini L, Panigada S, et al. Catheter ablation of atrial fibrillation in patients with diabetes mellitus type 2: results from a randomized study comparing pulmonary vein isolation versus antiarrhythmic drug therapy. J Cardiovasc Electrophysiol. 2009;20(1):22-8. doi:10.1111/j.1540-8167.2008.01275.x.\u003c/li\u003e\n\u003cli\u003eWazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, et al. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med. 2021;384(4):316-24. doi:10.1056/NEJMoa2029554.\u003c/li\u003e\n\u003cli\u003eWilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, et al. Comparison of Antiarrhythmic Drug Therapy and Radiofrequency Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation A Randomized Controlled Trial. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. 2010;303(4):333-40. doi:10.1001/jama.2009.2029.\u003c/li\u003e\n\u003cli\u003eWu G, Huang H, Cai L, Yang YZ, Liu X, Yu B, et al. Long-term observation of catheter ablation vs. pharmacotherapy in the management of persistent and long-standing persistent atrial fibrillation (CAPA study). EUROPACE. 2021;23(5):731-9. doi:10.1093/europace/euaa356.\u003c/li\u003e\n\u003cli\u003eKheshti F, Abdollahifard S, Hosseinpour A, Bazrafshan M, Attar A. Ablation versus medical therapy for patients with atrial fibrillation: An updated meta-analysis. CLIN CARDIOL. 2024;47(2). doi:10.1002/clc.24184.\u003c/li\u003e\n\u003cli\u003eYounes H, Sohns C, Akoum N, Feng H, Tsakiris E, Hajjar AHE, et al. Sex-specific outcomes and left atrial remodeling following catheter ablation of persistent atrial fibrillation: results from the DECAAF II trial. J Interv Card Electrophysiol. 2024;67(8):1843-50. doi:10.1007/s10840-024-01831-w.\u003c/li\u003e\n\u003cli\u003eRujirachun P, Wattanachayakul P, Taveeamornrat S, Ungprasert P, Tokavanich N, Jongnarangsin K. Atrial Fibrillation Recurrence Risk After Catheter Ablation in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Clin Cardiol. 2025;48(1):e70021. doi:10.1002/clc.70021.\u003c/li\u003e\n\u003cli\u003eAng R, Domenichini G, Finlay MC, Schilling RJ, Hunter RJ. The Hot and the Cold: Radiofrequency Versus Cryoballoon Ablation for Atrial Fibrillation. Curr Cardiol Rep. 2015;17(9). doi:10.1007/s11886-015-0631-7.\u003c/li\u003e\n\u003cli\u003eZhang Z, Letsas KP, Zhang N, Efremidis M, Xu G, Li G, et al. Linear Ablation Following Pulmonary Vein Isolation in Patients with Atrial Fibrillation: A Meta-Analysis. PACE Pacing Clin Electrophysiol. 2016;39(6):623-30. doi:10.1111/pace.12841\u003cstrong\u003e.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anti-Arrhythmia Agents, Atrial Fibrillation, Catheter Ablation. (MESH)","lastPublishedDoi":"10.21203/rs.3.rs-7820043/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7820043/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAtrial fibrillation (AF) is the most common cardiac arrhythmia associated with increased morbidity and mortality. While catheter ablation and antiarrhythmic drug (AAD) therapy are both established treatment options, their comparative efficacy and safety remain debated.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis systematic review and meta-analysis evaluated the effectiveness and safety of catheter ablation versus AAD therapy in adults with AF.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA comprehensive search of PubMed, Scopus, Embase, and Web of Science was conducted for randomized controlled trials (RCTs) comparing catheter ablation (radiofrequency or cryoballoon) with AAD therapy. Primary outcomes included atrial arrhythmia recurrence and progression to persistent AF. Secondary outcomes encompass serious adverse events, reintervention rates, and procedure-related complications. Risk of bias was assessed using the RoB 2.0 tool, and certainty of evidence was evaluated using the GRADE framework.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 24 RCTs involving 9,507 patients were included. Catheter ablation significantly reduced atrial arrhythmia recurrence (RR: 0.57; 95% CI: 0.44\u0026ndash;0.73) and progression to persistent AF (RR: 0.12; 95% CI: 0.06\u0026ndash;0.24). No difference in serious adverse events was observed between groups (RR: 1.00; 95% CI: 0.84\u0026ndash;1.19). However, catheter ablation was associated with a higher risk of reintervention (RR: 36.04; 95% CI: 16.10\u0026ndash;80.65) and procedure-related complications (RR: 8.52; 95% CI: 3.12\u0026ndash;23.27). Side effects were significantly lower in the ablation group than in AAD therapy (RR: 0.04; 95% CI: 0.01\u0026ndash;0.10).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCatheter ablation demonstrates superior efficacy in reducing arrhythmia recurrence and preventing progression to persistent AF, with a comparable safety profile to AAD therapy. However, the increased risk of reintervention and procedural complications highlights the need for careful patient selection and shared decision-making.\u003c/p\u003e","manuscriptTitle":"Catheter Ablation vs Antiarrhythmic Agents in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-15 16:44:52","doi":"10.21203/rs.3.rs-7820043/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-12-10T20:29:24+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-10T18:27:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-01T02:52:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Systematic Reviews","date":"2025-10-09T13:28:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b426e8dc-b03e-4268-ac28-fc5b4c130d43","owner":[],"postedDate":"December 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:44:52+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-15 16:44:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7820043","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7820043","identity":"rs-7820043","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}