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Reviews in Cardiovascular Medicine  2020, Vol. 21 Issue (3): 419-432     DOI: 10.31083/j.rcm.2020.03.60
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Meta-analysis of medical management versus catheter ablation for atrial fibrillation
Yin-jun Mao1, Hang Wang1, Jian-xing Chen2, Pin-fang Huang1, *()
1Department of Pharmacy, First Affiliated Hospital of Fujian Medical University, Chazhong Road NO.20, Fuzhou, 350000, Fujian, P. R. China
2Department of Anesthesiology, First Affiliated Hospital of Fujian Medical University, Chazhong Road NO.20, Fuzhou, 350000, Fujian, P. R. China
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Abstract:

Several observational studies have shown a survival benefit for patients with atrial fibrillation (AF) who are treated with catheter ablation (CA) rather than medical management (MM). However, data from randomized controlled trials (RCTs) are uncertain. Therefore, we performed a meta-analysis of RCTs that compared the benefits of CA and MM in treatment of AF. We searched the Cochrane Library, PubMed, and EMBASE databases for RCTs that compared AF ablation with MM from the time of database establishment up to January 2020. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure treatment effect. Twenty-six RCTs that enrolled a total of 5788 patients were included in the meta-analysis. In this meta-analysis, the effect of AF ablation depended on the baseline level of left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. AF ablation appears to be of benefit to patients with a lesser degree of advanced HF and better LVEF by reducing mortality. Meanwhile, this mortality advantage was manifested in long-term follow-up. CA increased the risk for hospitalization when it was used as first-line therapy and decreased the risk when used as second-line therapy. CA reduced recurrence of atrial arrhythmia for different types of AF (paroxysmal or persistent AF) and CA-related complications were non-negligible. There was no convincing evidence for a reduction in long-term stroke risk after AF ablation, and additional high quality RCTs are needed to address that issue.

Key words:  Atrial fibrillation      medical management      catheter ablation      stroke      mortality     
Submitted:  14 April 2020      Revised:  25 June 2020      Accepted:  09 July 2020      Published:  30 September 2020     
*Corresponding Author(s):  Pin-fang Huang     E-mail:  huangpinfang@fjmu.edu.cn

Cite this article: 

Yin-jun Mao, Hang Wang, Jian-xing Chen, Pin-fang Huang. Meta-analysis of medical management versus catheter ablation for atrial fibrillation. Reviews in Cardiovascular Medicine, 2020, 21(3): 419-432.

URL: 

https://rcm.imrpress.com/EN/10.31083/j.rcm.2020.03.60     OR     https://rcm.imrpress.com/EN/Y2020/V21/I3/419

Fig. 1.  Flow diagram showing the study selection process for the meta-analysis. The number of studies shown at the bottom of the flow chart represents studies that were ultimately considered eligible for inclusion in this meta-analysis.

Table 1.  Baseline characteristics of the included trials.
Study/Year Patients (n) Mean age (years) Male (%) LAD (mm) LVEF (%) PEE (n) CAD (n) DM (n) HTN (n) Crossover to CA(%) Follow up (months)
Natale et al., 2000 31/30 67 ± 8/66 ± 11 65/73 NR 49.4 ± 5/49.6 ± 3 NR 12/11 NR NR NR 33
Krittayaphong et al., 2003 15/15 55 ± 11/49 ± 15 73/53 39.6 ± 7.7/39.2 ± 7.1 63.7 ± 10/61.8 ± 9 0/0 NR NR NR NR 12
Wazni et al., 2005 33/37 53 ± 8/54 ± 8 NR 41 ± 8/42 ± 7 53 ± 5/54 ± 6 NR NR NR 8/10 NR 12
Da Costa et al., 2006 52/51 78.5 ± 5/78 ± 5 79/82 43 ± 7/43 ± 6 56 ± 14/54 ± 14 NR NR 10/11 36/34 NR 13
Oral et al., 2006 77/69 55 ± 9/58 ± 8 67/62 45 ± 6/45 ± 5 55 ± 7/56 ± 7 0/0 3/4 NR NR 77 12
Stabile et al., 2006 68/69 62 ± 9/62 ± 11 54/64 46 ± 5/45.4 ± 5.5 59.1 ± 6.7/57.9 ± 5.8 NR NR NR 36/34 52 12
Pappone et al., 2006 99/99 55 ± 10/57 ± 10 70/65 40 ± 6/38 ± 6 60 ± 8/61 ± 6 NR 2/2 5/4 56/57 42 12
Jais et al., 2008 53/59 50 ± 11/52 ± 11 85/83 39.5 ± 6/40 ± 6 63 ± 11/66 ± 7 1/7 NR 1/2 11/18 63 12
Forleo et al., 2009 35/35 63 ± 9/65 ± 7 57/65 44 ± 6/45.2 ± 5 54.6 ± 7/52.6 ± 9 5/3 7/7 35/35 22/24 NR 12
Wilber et al., 2010 106/61 56 ± 9/56 ± 13 69/62 40 ± 1.1/40 ± 1.5 62.3 ± 2/62.7 ± 2 2/2 NR 10/7 51/30 59 9
MacDonald et al., 2011 22/19 62 ± 7/64 ± 8 77/79 NR 16.1 ± 7.1/19.6 ± 5.5 2/2 11/9 7/4 14/11 0 6
Nielsen et al., 2012 146/148 56 ± 9/54 ± 10 68/72 40 ± 6/40 ± 5 >60/>60 6/5 6/2 6/10 43/53 36 24
Packer et al., 2013 163/82 57 ± 9/56 ± 9 77/78 40 ± 5/41 ± 6 60 ± 6/61 ± 6 0/0 13/8 11/7 67/37 79 12
Pokushalov et al., 2013 77/77 56 ± 7/57 ± 7 73/77 45 ± 7/46 ± 5 57 ± 6/58 ± 5 5/6 8/10 9/7 24/29 56 36
Jones et al., 2013 26/26 64 ± 10/62 ± 9 81/92 50 ± 6/46 ± 7 22 ± 8/25 ± 7 NR 11/13 NR NR 3.8 12
Zhang et al., 2014 101/100 60 ± 11/58 ± 10 70/67 45.8 ± 6/45.7 ± 6 57.9 ± 6/57.5 ± 7 10/6 11/13 19/20 52/48 24 24
Mont et al., 2014 98/48 55 ± 9/55 ± 9 78/77 41 ± 5/42 ± 5 61 ± 8/60 ± 9 4/2 NR NR 46/19 48 12
Hummel et al., 2014 138/72 60 ± 8/61 ± 8 83/83 45 ± 5/46 ± 5 54 ± 7/55 ± 6 0/0 28/12 22/8 84/40 60 6
Hunter et al., 2014 26/24 55 ± 12/60 ± 10 96/96 52 ± 11/50 ± 10 31.8 ± 7.7/33.7 ± 12 NR NR NR 8/8 0 6
Morillo et al., 2014 66/61 56 ± 9/54 ± 12 77/74 40 ± 5/43 ± 5 61.4 ± 5/60.8 ± 7 3/4 6/2 1/4 28/25 43 24
Sohara et al., 2016 100/43 59 ± 10/61 ± 10 80/81 38.3 ± 6/38.3 ± 5 66.7 ± 6/66.5 ± 7 NR 3/2 3/4 51/24 79 9
Di Biase et al., 2016 102/101 62 ± 10/60 ± 11 75/73 47 ± 4.2/48 ± 4.9 29 ± 5/30 ± 8 NR 63/66 22/24 46/48 NR 24
Prabhu et al., 2017 33/33 59 ± 11/62 ± 9 94/88 48 ± 5.5/47 ± 8.2 32 ± 9/34 ± 8 2/0 0/0 4/5 13/12 9 6
Marrouche et al., 2018 179/184 64 ± 3/64 ± 3 87/84 48 ± 1.5/49.5 ± 8.3 31.5 ± 1.7/32.5 ± 2.2 21/21 72/96 43/67 129/136 15.6 38
Packer et al., 2019 1108/1096 68 ± 5/67 ± 5 63/63 NR NR 117/103 201/216 280/281 876/900 27.5 48
Kuck et al., 2019 100/95 65 ± 8/65 ± 8 88/92 50 ± 6/51 ± 5 28 ± 9.5/24 ± 8.8 NR 30/40 24/22 56/55 4 12
Data are presented as patients receiving CA/patients receiving MM. Age is given as mean ± SD. CA: catheter ablation; CAD: coronary artery disease; DM: diabetes mellitus; HTN: hypertension; LAD: left atrial diameter; LVEF: left ventricular ejection fraction; MM: medical management; NR: not reported; PEE: previous embolic events.
Table 2.  Risks of bias in the included trials according to the Cochrane risk of bias assessment tool.
Author/Study(year) Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personnel (performance bias) Blinding of outcome assessment (detection bias) Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Other bias
Natale et al., 2000 Unlcear Low High High Low Low Unlcear
Krittayaphong et al., 2003 Unclear Unclear Unclear Unclear Unclear Unclear Unclear
Wazni et al., 2005 Low High Unclear Unclear Low Low Unclear
Da Costa et al., 2006 Unclear Unclear Unclear Unclear Unclear Unclear Unclear
Oral et al., 2006 Low Unclear Unclear Unclear Low Unclear High
Stabile et al., 2006 Low Unclear High Low Low Low High
Pappone et al., 2006 Unclear Unclear High Low Low Low Unclear
Jais et al., 2008 Low Unclear Low Unlcear Low Low High
Forleo et al., 2009 Low High Unclear Unlcear Low Low Unlcear
Wilber et al., 2010 Low Low High Unlcear Low Low High
MacDonald et al., 2011 Low Low High High Low Low Unclear
Nielsen et al., 2012 Low Low High Low Low Low Unclear
Packer et al., 2013 Unlcear Low High Unclear High Low High
Pokushalov et al., 2013 Low Low High Low Low Low High
Jones et al., 2013 Low High High Low Low Low Unclear
Zhang et al., 2014 Low High High Low Low Low Unclear
Mont et al., 2014 Low High High Unclear Low Low Unclear
Hummel et al., 2014 Unclear Unclear Unclear Unclear Low Unclear High
Hunter et al., 2014 Low Low High High Low Low Unclear
Morillo et al., 2014 Low Unclear Unclear Low Low Low Unclear
Sohara et al., 2016 Unlcear Unclear High Low High Low High
Di Biase et al., 2016 Low Low High High High Low Unlcear
Prabhu et al., 2017 Low Low High High Low Low Unlcear
Marrouche et al., 2018 Low Low High Unclear High Low Unlcear
Packer et al., 2019 Low Low High Low Low Low Unlcear
Kuck et al., 2019 Low Low High Low High Low Unlcear
Fig. 2.  The pooled outcome of all-cause mortality. A forest plot illustrating the all-cause mortality during follow-up among AF patients randomized to CA versus MM. Packer-(Non-HF), Packer-(HF), and Marrouche-(AHF) used composite endpoints.

Fig. 3.  Sensitivity analysis for all-cause mortality. (A) Sensitivity analysis for all-cause mortality among patients without HF. (B) Sensitivity analysis for all-cause mortality among patients with HF. (C) Sensitivity analysis for all-cause mortality among patients with AHF.

Fig. 4.  The pooled outcome of hospitalization risk for patients treated with CA versus MM. A forest plot illustrating results of the subgroup analysis that was performed based on CA provided as first-line or second-line therapy (upper panel shows the pooled outcome for CA when used as first-line therapy; lower panel shows the pooled outcome for CA when used as second-line therapy).

Fig. 5.  The pooled outcome of hospitalization risk when CA was used as first-line therapy. A forest plot illustrating the risk of hospitalization when CA was performed as first-line treatment, after excluding the study by Wazni et al. (2005).

Fig. 6.  The pooled outcome of stroke/TIA risk associated with CA versus MM. The forest plot illustrates results of a subgroup analysis that was performed based on the source of stroke (upper panel shows the pooled outcome for stroke directly induced by AF itself; lower panel shows the pooled outcome for stroke caused by ablation procedure).

Fig. 7.  The pooled outcome of peri-procedural complications in the CA group versus the MM group. The forest plot illustrates results of the stratification analysis that was performed based on the types of complications (upper panel shows the pooled outcome for major bleeding, the middle panel shows the pooled outcome for pulmonary vein stenosis, and lower panel shows the pooled outcome for pericardial complications).

Table 3.  Complications related to CA.
Death, N (%) Stroke/ TIA, N (%) Major bleeding, N (%) Pulmonary vein stenosis, N (%) Pericardial complications, N (%)
Natale (N = 31) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Krittayaphong (N = 15) 0 (0.0%) 1 (6.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Wazni (N = 33) 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (6.1%) 0 (0.0%)
Da Costa (N = 52) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Oral (N = 77) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Stabile (N = 68) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (1.5%)
Pappone (N = 99) 0 (0.0%) 1 (1.0%) 0 (0.0%) 0 (0.0%) 1 (1.0%)
Jais (N = 53) 0 (0.0%) 0 (0.0%) 2 (3.8%) 1 (1.9%) 2 (3.8%)
Forleo (N = 35) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Wilber (N = 106) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.9%)
MacDonald (N = 22) 0 (0.0%) 0 (0.0%) 2 (9.1%) 0 (0.0%) 2 (9.1%)
Nielsen (N = 146) 1 (0.7%) 1 (0.7%) 0 (0.0%) 1 (0.7%) 3 (2.1%)
Packer (2013) (N = 163) 0 (0.0%) 1 (0.6%) 3 (1.8%) 5 (3.1%) 1 (0.6%)
Pokushalov (N = 77) 0 (0.0%) 0 (0.0%) 2 (2.6%) 0 (0.0%) 2 (2.6%)
Jones (N = 25) 0 (0.0%) 0 (0.0%) 1 (4.0%) 0 (0.0%) 1 (4.0%)
Zhang (N = 101) 0 (0.0%) 2 (2.0%) 1 (1.0%) 0 (0.0%) 1 (1.0%)
Mont (N = 98) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (1.0%) 3 (3.1%)
Hummel (N = 138) 0 (0.0%) 4 (2.9%) 0 (0.0%) 5 (3.6%) 5 (3.6%)
Hunter (N = 26) 0 (0.0%) 1 (3.8%) 1 (3.8%) 0 (0.0%) 1 (3.8%)
Morillo (N = 66) 0 (0.0%) 0 (0.0%) 4 (6.0%) 1 (1.5%) 4 (6.1%)
Sohara (N = 100) 0 (0.0%) 2 (2.0%) 0 (0.0%) 7 (7.0%) 0 (0.0%)
Di Biase (N = 102) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (1.0%)
Prabhu (N = 33) 0 (0.0%) 0 (0.0%) 2 (6.0%) 0 (0.0%) 0 (0.0%)
Marrouche (N = 179) 0 (0.0%) 0 (0.0%) 4 (2.2%) 1 (0.6%) 3 (1.7%)
Packer (2019) (N = 1108) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 (0.09%) 8 (0.7%)
Kuck (N = 98) 1 (1.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 2 (2.0%)
Total (N = 3051) 2 (0.06%) 13 (0.4%) 22 (0.7%) 25 (0.8%) 42 (1.4%)
Table 4.  Outcome for recurrence of atrial arrhythmia in AF patients with normal or reduced LVEF who underwent CA or MM in the included trials.
Recurrence of atrial arrhythmia No. of studies Patients CA/MM Events CA/MM P value Effect estimate RR (95% CI) I2 Incidence after CA/MM
Overall 26 2533/2249 882/1525 < 0.00001 0.43 (0.37, 0.51) 82% 34.8%/67.8%
Follow-up duration
Follow-up 1 year 20 2113/2003 730/1309 < 0.00001 0.43 (0.36, 0.53) 83% 34.5%/65.4%
Follow-up 2 years 8 1313/1330 531/858 < 0.00001 0.58 (0.48, 0.69) 72% 40.4%/64.5%
Follow-up 3 years 3 867/890 398/623 0.001 0.60 (0.45, 0.82) 85% 45.9%/70%
Follow-up 4 years 1 611/629 305/437 < 0.00001 0.72 (0.65, 0.79) 49.9%/69.5%
Type of MM
CA vs. rhythm control 14 992/863 291/617 < 0.00001 0.38 (0.30, 0.49) 76% 29.3%/71.5%
CA vs. rate control 4 104/101 18/99 0.008 0.17 (0.05, 0.63) 88% 17.3%/98%
Number of ablation
Single ablation 12 756/606 311/481 < 0.00001 0.51 (0.45, 0.58) 46% 41.1%/79%
Multiple ablations 19 2330/2102 804/1401 < 0.00001 0.45 (0.38, 0.54) 83% 34.5%/66.7%
Type of AF
Paroxysmal AF 7 864/799 287/527 0.0001 0.43 (0.29, 0.66) 93% 33.2%/66%
Persistent AF 8 803/743 308/475 < 0.00001 0.54 (0.44, 0.68) 66% 38.4%/63.9%
Level of LVEF
Normal LVEF 19 1966/1675 696/1116 < 0.00001 0.44 (0.37, 0.54) 83% 35.4%/66.6%
Reduced LVEF 8 567/566 186/409 < 0.00001 0.42 (0.30, 0.60) 81% 32.8%/72.2%
AF: atrial fibrillation; CA: catheter ablation; CI: confidence interval; LVEF: left ventricular ejection fraction; MM: medical management; RR: risk ratio.
Fig. 8.  A Begg’s funnel plot of all studies included in the meta-analysis. The absence of asymmetry indicates that there was no publication bias.

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