Meta-analysis of medical management versus catheter ablation for atrial fibrillation

doi:10.31083/j.rcm.2020.03.60

Reviews in Cardiovascular Medicine

2020, Vol. 21

Issue (3): 419-432 DOI: 10.31083/j.rcm.2020.03.60

Systematic Review

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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 Huang^1,^*(

)

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

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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.

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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 $\pm$ 8/66 $\pm$ 11	65/73	NR	49.4 $\pm$ 5/49.6 $\pm$ 3	NR	12/11	NR	NR	NR	33
Krittayaphong et al., 2003	15/15	55 $\pm$ 11/49 $\pm$ 15	73/53	39.6 $\pm$ 7.7/39.2 $\pm$ 7.1	63.7 $\pm$ 10/61.8 $\pm$ 9	0/0	NR	NR	NR	NR	12
Wazni et al., 2005	33/37	53 $\pm$ 8/54 $\pm$ 8	NR	41 $\pm$ 8/42 $\pm$ 7	53 $\pm$ 5/54 $\pm$ 6	NR	NR	NR	8/10	NR	12
Da Costa et al., 2006	52/51	78.5 $\pm$ 5/78 $\pm$ 5	79/82	43 $\pm$ 7/43 $\pm$ 6	56 $\pm$ 14/54 $\pm$ 14	NR	NR	10/11	36/34	NR	13
Oral et al., 2006	77/69	55 $\pm$ 9/58 $\pm$ 8	67/62	45 $\pm$ 6/45 $\pm$ 5	55 $\pm$ 7/56 $\pm$ 7	0/0	3/4	NR	NR	77	12
Stabile et al., 2006	68/69	62 $\pm$ 9/62 $\pm$ 11	54/64	46 $\pm$ 5/45.4 $\pm$ 5.5	59.1 $\pm$ 6.7/57.9 $\pm$ 5.8	NR	NR	NR	36/34	52	12
Pappone et al., 2006	99/99	55 $\pm$ 10/57 $\pm$ 10	70/65	40 $\pm$ 6/38 $\pm$ 6	60 $\pm$ 8/61 $\pm$ 6	NR	2/2	5/4	56/57	42	12
Jais et al., 2008	53/59	50 $\pm$ 11/52 $\pm$ 11	85/83	39.5 $\pm$ 6/40 $\pm$ 6	63 $\pm$ 11/66 $\pm$ 7	1/7	NR	1/2	11/18	63	12
Forleo et al., 2009	35/35	63 $\pm$ 9/65 $\pm$ 7	57/65	44 $\pm$ 6/45.2 $\pm$ 5	54.6 $\pm$ 7/52.6 $\pm$ 9	5/3	7/7	35/35	22/24	NR	12
Wilber et al., 2010	106/61	56 $\pm$ 9/56 $\pm$ 13	69/62	40 $\pm$ 1.1/40 $\pm$ 1.5	62.3 $\pm$ 2/62.7 $\pm$ 2	2/2	NR	10/7	51/30	59	9
MacDonald et al., 2011	22/19	62 $\pm$ 7/64 $\pm$ 8	77/79	NR	16.1 $\pm$ 7.1/19.6 $\pm$ 5.5	2/2	11/9	7/4	14/11	0	6
Nielsen et al., 2012	146/148	56 $\pm$ 9/54 $\pm$ 10	68/72	40 $\pm$ 6/40 $\pm$ 5	$>$ 60/ $>$ 60	6/5	6/2	6/10	43/53	36	24
Packer et al., 2013	163/82	57 $\pm$ 9/56 $\pm$ 9	77/78	40 $\pm$ 5/41 $\pm$ 6	60 $\pm$ 6/61 $\pm$ 6	0/0	13/8	11/7	67/37	79	12
Pokushalov et al., 2013	77/77	56 $\pm$ 7/57 $\pm$ 7	73/77	45 $\pm$ 7/46 $\pm$ 5	57 $\pm$ 6/58 $\pm$ 5	5/6	8/10	9/7	24/29	56	36
Jones et al., 2013	26/26	64 $\pm$ 10/62 $\pm$ 9	81/92	50 $\pm$ 6/46 $\pm$ 7	22 $\pm$ 8/25 $\pm$ 7	NR	11/13	NR	NR	3.8	12
Zhang et al., 2014	101/100	60 $\pm$ 11/58 $\pm$ 10	70/67	45.8 $\pm$ 6/45.7 $\pm$ 6	57.9 $\pm$ 6/57.5 $\pm$ 7	10/6	11/13	19/20	52/48	24	24
Mont et al., 2014	98/48	55 $\pm$ 9/55 $\pm$ 9	78/77	41 $\pm$ 5/42 $\pm$ 5	61 $\pm$ 8/60 $\pm$ 9	4/2	NR	NR	46/19	48	12
Hummel et al., 2014	138/72	60 $\pm$ 8/61 $\pm$ 8	83/83	45 $\pm$ 5/46 $\pm$ 5	54 $\pm$ 7/55 $\pm$ 6	0/0	28/12	22/8	84/40	60	6
Hunter et al., 2014	26/24	55 $\pm$ 12/60 $\pm$ 10	96/96	52 $\pm$ 11/50 $\pm$ 10	31.8 $\pm$ 7.7/33.7 $\pm$ 12	NR	NR	NR	8/8	0	6
Morillo et al., 2014	66/61	56 $\pm$ 9/54 $\pm$ 12	77/74	40 $\pm$ 5/43 $\pm$ 5	61.4 $\pm$ 5/60.8 $\pm$ 7	3/4	6/2	1/4	28/25	43	24
Sohara et al., 2016	100/43	59 $\pm$ 10/61 $\pm$ 10	80/81	38.3 $\pm$ 6/38.3 $\pm$ 5	66.7 $\pm$ 6/66.5 $\pm$ 7	NR	3/2	3/4	51/24	79	9
Di Biase et al., 2016	102/101	62 $\pm$ 10/60 $\pm$ 11	75/73	47 $\pm$ 4.2/48 $\pm$ 4.9	29 $\pm$ 5/30 $\pm$ 8	NR	63/66	22/24	46/48	NR	24
Prabhu et al., 2017	33/33	59 $\pm$ 11/62 $\pm$ 9	94/88	48 $\pm$ 5.5/47 $\pm$ 8.2	32 $\pm$ 9/34 $\pm$ 8	2/0	0/0	4/5	13/12	9	6
Marrouche et al., 2018	179/184	64 $\pm$ 3/64 $\pm$ 3	87/84	48 $\pm$ 1.5/49.5 $\pm$ 8.3	31.5 $\pm$ 1.7/32.5 $\pm$ 2.2	21/21	72/96	43/67	129/136	15.6	38
Packer et al., 2019	1108/1096	68 $\pm$ 5/67 $\pm$ 5	63/63	NR	NR	117/103	201/216	280/281	876/900	27.5	48
Kuck et al., 2019	100/95	65 $\pm$ 8/65 $\pm$ 8	88/92	50 $\pm$ 6/51 $\pm$ 5	28 $\pm$ 9.5/24 $\pm$ 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 $\pm{}$ 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.

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.

Follow-up duration
Recurrence of atrial arrhythmia	No. of studies	Patients CA/MM	Events CA/MM	P value	Effect estimate RR (95% CI)	I ${}^{2}$	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 $\geq$ 1 year	20	2113/2003	730/1309	$<$ 0.00001	0.43 (0.36, 0.53)	83%	34.5%/65.4%
Follow-up $\geq$ 2 years	8	1313/1330	531/858	$<$ 0.00001	0.58 (0.48, 0.69)	72%	40.4%/64.5%
Follow-up $\geq$ 3 years	3	867/890	398/623	0.001	0.60 (0.45, 0.82)	85%	45.9%/70%
Follow-up $\geq$ 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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