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Safety and efficacy of direct oral anticoagulation in patients with and without radiofrequency ablation of non-valvular atrial fibrillation: a multicenter retrospective cohort study

Thrombosis Journal volume 21, Article number: 37 (2023) Cite this article

Abstract

Background

Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs.

Methods

This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death.

Results

After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P<0.001], thrombosis [OR 0.535 (95% CI, 0.316-0.908), P=0.020] and the composite endpoint [ OR 0.835 (95% CI, 0.710-0.982), P=0.029]. In the RFA PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. In the no RFA PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 ( 95% CI, 0.535-0.811), P<0.001].

Conclusion

Among patients with NVAF treated with DOACs, RFA was a negative correlate of major bleeding, thrombosis, and composite endpoints but was not associated with total bleeding or all-cause mortality.

Introduction

Atrial fibrillation (AF) is a common arrhythmia worldwide and is a major cause of cardiogenic ischemic stroke and systemic thrombosis (SE) [1, 2]. Patients with AF have a higher incidence of stroke and thromboembolic events than patients with sinus rhythm, significantly impacting morbidity and mortality [3]. Prevent thromboembolism, oral anticoagulants (OAC) are one of the preferred treatments for patients at risk of thromboembolism [4].

Catheter ablation (CA) is the most effective treatment to prevent the recurrence of AF [5], and it has made significant advances in safety and efficacy over the past decade [6,7,8,9,10]. However, CA is also at risk of thrombotic and bleeding events in the perioperative [11, 12]. In patients undergoing CA, perioperative complications are approximately 4%-14%, of which 2%-3% may be life-threatening [13]. A global survey on perioperative complications also showed that major complications occurred in 4.5% of patients treated with CA for AF (2.8% for major bleeding and 0.94% for thromboembolic events) [14]. Therefore, continued anticoagulation with OAC is recommended in the perioperative period of AF ablation [15, 16]. And several trials have shown that using uninterrupted perioperative anticoagulant warfarin or DOACs reduces the incidence of thromboembolic events without increasing the risk of major bleeding [17,18,19,20].

In addition, the 2020 European Society of Cardiology (ESC) guidelines recommend anticoagulation for at least 2 months after CA, which should be determined based on the patient's stroke risk profile [13]. Reducing the burden of AF with CA may help reduce ischemic stroke risk [21]. However, anticoagulation afterward requires attention to the adverse events associated with DOACs, including serious bleeding. Therefore the results of studies on the clinical benefits of continuous DOAC therapy need to be followed.

Based on the lack of available studies on the prognostic benefit of using DOACs after ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs.

Method

Study design

From January 2016 to December 2020, we conducted a multicenter retrospective registration at 15 centers in China (Supplementary Table 1). Supplementary Fig. 1 shows the distribution map of multicenter hospitals. The study registration number is ChiCTR2000031909. The inclusion criteria for this study were as follows: (1) age ≥18 years old; (2) diagnosis of NVAF; (3) treatment with DOACs; (4) patients with known ablation status and follow-up data during hospitalization at baseline. Exclusion criteria were: (1) patients with valvular AF; (2) taking warfarin or aspirin after discharge from the hospital. (3) Patients with incomplete basic data such as age and sex. Since apixaban has no indication for NVAF in China and edoxaban will only be available in China in 2019, the DOACs used in multicenter hospitals are rivaroxaban and dabigatran. A total of 6137 patients with NVAF treated with DOACs were eligible for this study after meeting the inclusion criteria. Of these, 2661 patients underwent radiofrequency ablation (RFA) during hospitalization, and 3476 did not undergo RFA.

Data collection and definition

Demographic information was collected through the hospital information system, and clinical events were obtained through follow-up visits to patients or their relatives. We collected basic statistics such as age, sex, height, weight, smoking and alcohol consumption, information on comorbid diseases such as hypertension, diabetes, coronary heart disease, vascular disease, liver and kidney insufficiency, and biochemical indices such as total bilirubin, glutathione, glutamic aminotransferase, and creatinine. Information on thrombotic and bleeding events and all-cause deaths after patients took DOACs was collected through follow-up. Based on the patient's clinical information, we performed the CHA2-VASC score [22] (congestive heart failure/left ventricular insufficiency, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, age 65-74 years and sex as female) and the HAS-BLED score [23] (hypertension, abnormal liver function, abnormal renal function, stroke, bleeding, age >65 years, drugs, alcohol).

Study outcomes

The primary outcomes of this study were major bleeding, total bleeding, thrombosis, all-cause death, and the composite endpoint of total bleeding, thrombosis, and all-cause death. The International Society on Thrombosis and Haemostasis (ISTH) defines hemorrhage as bleeding leading to death, occurring in a critical organ (intracranial, intra-spinal, intra-ocular, retroperitoneal, intra-articular or intra-pericardial, intra-muscular with fascial compartment syndrome) or with a decrease in hemoglobin level of at least 2 g/dl or transfusion of at least 2 units of red blood cells [24]. Total bleeding includes all bleeding events, including major and minor bleeding. Thrombotic events include stroke, venous thromboembolism, and other sites of thrombosis. Venous thromboembolism was defined as any symptomatic or incidental finding of lower or upper extremity proximal deep vein thrombosis, any non-fatal symptomatic or incidental pulmonary embolism, and death associated with pulmonary embolism [25].

Statistical analysis

Descriptive statistics are expressed as mean ± standard deviation (SD) for continuous variables and as counts or percentages for discrete variables. Continuous variables were tested for normality, t-tests were used to compare the differences in continuous variables between the two groups of patients if they conformed to a normal distribution; if they did not conform to a normal distribution, non-parametric statistical tests were used. The chi-square test was used to compare the distribution of categorical variables. Logistic regression was used to analyze potential confounders affecting major bleeding, total bleeding, thrombosis, all-cause mortality, and composite endpoints, and covariates included: age, sex, body mass index (BMI), smoking, alcohol consumption, hypertension, diabetes mellitus, heart failure, coronary artery disease, renal insufficiency, hepatic insufficiency, vascular disease, Total Bilirubin (TBIL), Aspartate transaminase (AST), Aspartate transaminase (ALT), creatinine, Platelet count (PLT), Hemoglobin (Hb), antiplatelet agents, Proton pump inhibitor (PPI), H2-blockers, statin, amiodarone, Proton pump inhibitor (ACEI), Angiotensin receptor blockers (ARB), β-receptor antagonists, Calcium Calcium Entry Blockers (CCB), diltiazem, and digoxin.

For further analysis, logistic regression of the variables in Supplementary table 2 was performed to obtain propensity score matching (PSM) to create comparable no-RFA and RFA cohorts in a 1:1 ratio. Nearest neighbor matching was performed using a caliper of 0.02 on the propensity score scale [26]. Since the propensity-matched dataset is a resampling from a sample representing the total, it is a sample within a sample. Whereas the hypothesis test corresponds to the aggregate in which the sample is located, the reduced sample size of the data after PSM would have resulted in a larger p-value. Therefore, standardized differences rather than statistical tests were used to assess the balance of covariates within the matched cohort. Standardized differences less than or equal to 0.1 indicate an adequate balance between groups [27]. If a covariate is unbalanced, we will check whether including it in the regression will affect the results.

Statistical analyses were performed using SPSS Statistics v. 22 (IBM Corporation, Armonk, NY, USA) and plotted using R software (R (4.1.1, R Core Team (2021)). Two-sided P values <0.05 were considered statistically significant.

Result

Baseline characteristics

A total of 6137 patients with NVAF [3619 (58.9%) male; mean age 63.7 ± 11.6] were included in this study, of whom 2661 patients [1734 (65.2) male; mean age 59.3 ± 10.5] underwent RFA at baseline and 3476 patients without RFA [1885 male (54.2); mean age 67.1 ± 11.3]. The inclusion flow chart is shown in Fig. 1.

Fig. 1
figure 1

Selection of the study population

Full size image

Table 1 shows the baseline information table of the patients. Compared with patients who did not receive RFA for NVAF, the group receiving RFA was younger, had more male patients, a slightly higher BMI, a lower burden of comorbid hypertension, diabetes, heart failure, coronary artery disease, hepatic and renal insufficiency, and vascular disease, and lower TIBL, AST, and creatinine values. Patients who underwent RFA had a lower risk of thrombosis and major bleeding than those who did not undergo RFA of NVAF [CHA2DS2-VASc mean 1.9 ± 1.2, HAS-BLED mean 1.3± 0.9]. Regarding combined medications, patients in the RFA group received more PPIs, amiodarone, and ACEIs and fewer antiplatelet agents, statins, ARBs, beta-blockers, diltiazem, and digoxin.

Table 1 Patient characteristics at baseline
Full size table

Outcomes

During a mean follow-up of 10 months, there were 670 bleeding events (10.9%), including 113 major bleeding events (1.8%), 83 thrombotic events (1.4%), 251 all-cause deaths (4.1%), and a composite endpoint of 979 (16.0%). The specific outcomes for the RFA and no RFA groups are shown in Table 2.

Table 2 Clinical Outcomes of RFA vs. no RFA in NVAF patients taking DOACs
Full size table

Bleeding events

The incidence of total bleeding was 9.9%, and major bleeding was 0.6% in the RFA group, and the incidence of total bleeding was 11.7%, and major bleeding was 2.8% in the no RFA group. The incidence of total bleeding [OR 0.839 (95% CI, 0.712-0.988), P<0.001] and major bleeding [OR 0.195 (95% CI, 0.113-0.337), P=0.035] was significantly lower in the RFA group compared with the no RFA group. After adjusting for confounding factors, the risk of total bleeding in patients with RFA was not significantly different from the no RFA group [OR 0.901 (95% CI, 0.746-1.087), P=0.275], but the risk of major bleeding remained significantly lower than in the no RFA group [OR 0.278 (95% CI, 0.150-0.515), P< 0.001]. The effects of RFA and potential risk factors on total bleeding in patients with NVAF are shown in Supplementary Fig. 2. Patients with combined coronary artery disease and higher creatinine are risk factors for total bleeding in NVAF patients, and combined use of β-blockers and CCB are protective factors. Supplementary Fig. 3 shows the effect of RFA and potential risk factors on major bleeding in patients with NVAF. Greater age, alcohol, combined diabetes mellitus, higher creatinine, and combined use of antiplatelet agents were risk factors for major bleeding in patients with NVAF. Protective factors were RFA, higher BMI, combined vascular disease, higher AST, combined PPI, H2-blockers, statins, ARB, β-blockers, and CCB.

Thrombosis events

The incidence of thrombosis was 0.9% in the RFA group and 1.7% in the no RFA. The incidence of thrombosis [OR 0.559 (95% CI, 0.349-0.896), P=0.014] was significantly lower in the RFA group compared with the no RFA group. After adjusting for confounding factors, the risk of thrombosis remained significantly lower in patients with RFA of NVAF than in the no RFA group [OR 0.535 (95% CI, 0.316-0.908), P=0.020]. The effects of RFA and potential risk factors on thrombosis in patients with NVAF are shown in Supplementary Fig. 4. Alcohol consumption was a risk factor for thrombosis in NVAF patients, and RFA was a protective factor.

All-cause death

The incidence of all-cause death [OR 0.523 (95% CI, 0.396-0.690), P<0.001] was significantly lower in the RFA group compared with the no RFA group. After adjusting for confounding factors, the risk of all-cause death in patients with RFA of NVAF was not significantly different from the no RFA group [OR 0.842 (95% CI, 0.611-1.160), P=0.293]. The effects of RFA and potential risk factors on all-cause death in patients with NVAF are shown in Supplementary Fig. 5. Male, greater age, combined diabetes mellitus, vascular disease, higher TBIL, and combined use of statin were risk factors for all-cause death in patients with NVAF, and higher BMI was a protective factor.

Composite outcome

The incidence of the composite endpoint [OR 0.704 (95% CI, 0.611-0.810), P<0.001] was significantly lower in the RFA group compared with the no RFA group. After adjusting for confounding factors, the risk of the composite endpoint remained significantly lower in patients with RFA of NVAF than in the no RFA group [OR 0.835 (95% CI, 0.710-0.982), P=0.029]. The effects of RFA and potential risk factors on the composite endpoint in patients with NVAF are shown in Supplementary Fig. 6. Comorbid heart failure and vascular disease are risk factors for the composite endpoint in patients with NVAF. RFA, higher BMI, and combined use of ARB, β-blockers, and CCB were protective factors.

PSM Cohort

We used PSM to identify 1700 patients with comparable baseline characteristics in both groups (Supplementary Table 2). In the PSM cohort, RFA was associated with a reduced risk of major bleeding [OR 0.290 (95% CI, 0.143-0.589), P<0.001], thrombosis [OR 0.509 (95% CI, 0.287-0.902), P=0.019] and composite endpoint [OR 0.818 (95% CI, 0.675-0.991), P= 0.040] (Table 3). There were no significant differences between the two groups regarding total bleeding and all-cause death.

Table 3 Clinical Outcomes of RFA vs. no RFA in NVAF patients taking DOACs after propensity score matching
Full size table

Subgroup analysis

We performed a subgroup analysis of the clinical outcomes of patients taking different DOACs (dabigatran, rivaroxaban) in the RFA group and no RFA group, respectively.

RFA group

Supplementary Table 3 is baseline information on the administration of rivaroxaban and dabigatran in patients with NVAF in the RFA group. We identified 773 patients in each group with comparable baseline characteristics with PSM. In the PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. There were no significant differences between rivaroxaban and dabigatran for major bleeding, total bleeding, thrombosis, and composite endpoints (Supplementary Table 4).

No RFA group

Supplementary Table 5 is baseline information for NVAF patients taking rivaroxaban and dabigatran in the no RFA group. We identified 1301 patients in each group with comparable baseline characteristics with PSM. In the PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 (95% CI, 0.535-0.811), P<0.001]. There was no significant difference between rivaroxaban and dabigatran regarding thrombosis and all-cause death (Supplementary Table 6).

Discussion

Our study is a multicenter retrospective cohort study based on 15 hospitals in China to investigate the difference in predictive outcomes between patients undergoing RFA and patients without RFA taking DOACs. Our study had the following findings: (1) During a mean follow-up of 10 months, RFA significantly affected major bleeding, thrombosis, and composite endpoints in NVAF patients taking DOACs. (2) Patients who underwent RFA had a reduced risk of major bleeding, thrombosis, and composite endpoints compared to patients without RFA. (3) Patients taking rivaroxaban versus dabigatran for RFA did not affect prognostic outcomes. (4) The risk of total bleeding, major bleeding, and composite endpoints was lower in patients without RFA taking rivaroxaban than on dabigatran.

Inconsistent results have been found in different studies regarding the benefits of ablation in patients with AF. In a Meta-analysis of 11 randomized controlled trials, CA of AF was found to reduce AF recurrence and improve quality of life compared with antiarrhythmic drug therapy but failed to change the risk of all-cause death, stroke, or TIA [28]. In contrast, a Meta-analysis of 9 studies by Saglietto et al. [29] found that CA reduced the risk of death, stroke, and hospitalization for heart failure compared to drug therapy alone. However, the benefits of ablation for patients with AF have been reported in several national observational studies in recent years. Mansour et al. [30] analyzed claims data and found a lower risk of thromboembolic events and cardiovascular hospitalization in patients with AF treated with CA compared with patients taking antiarrhythmic drugs. Srivatsa et al. [31] found that ablation was associated with lower mortality, ischemic stroke, and hemorrhagic stroke in a US population-based study of hospitalized patients with NVAF. A propensity-matched study by Saliba et al. [32] using a computerized database of the largest health maintenance organization in Israel, found that CA of AF was associated with reduced stroke/TIA and mortality in patients with higher CHA2DS2-Vasc scores. A study by Kim et al. [33] using the Korean National Health Insurance (NHIS) database showed that CA significantly reduced the risk of ischemic stroke and major bleeding compared with drug therapy.

However, the benefit of RFA for NVAF patients taking DOACs is currently poorly reported. Ding et al. [34] analyzed phase II/III data from the GLORIA-AF (GLORIA-AF is a prospective, observational, global registry programme of patients from 935 centers across 38 participating countries in Asia, Europe, North America, Latin America, and Africa/Middle East.) found that early AF ablation was associated with all-cause death and the composite endpoints of stroke, major bleeding, and all-cause death in patients treated with NOAC compared with drug therapy alone. In contrast to the previous study, we investigated the difference in outcomes of DOACs in NVAF patients who underwent RFA and those without RFA in 15 centers in China. We found that RFA was significantly associated with a reduction in the composite endpoint of bleeding, thrombosis. Still, we found that RFA was significantly associated with a reduction in major bleeding and thrombosis. The discrepancy may be due to the small number of patients with NVAF who underwent ablation, 445, including Ding et al. [34], and nearly 30% of these patients did not receive NOAC treatment. It may also be because Ding et al. included patients with generally higher age, BMI, and CHA2DS2-VASc scores, which may have had a greater impact on the results. In addition, the covariates included in the analysis in this study differ from those in Ding's study [34], which may impact the results after adjusting for confounding factors. RFA reduces the incidence of thrombosis possibly by restoring and maintaining sinus rhythm (SR) in patients with NVAF, thereby restoring atrial contraction, which may facilitate a reduction in the prothrombotic state, leading to a reduced risk of thrombosis [35]. In addition, the reduced thrombotic risk in NVAF patients receiving RFA may be accompanied by a reduction in DOAC use, which consequently reduces the risk of major bleeding and the occurrence of composite endpoints.

We analyzed the factors influencing total bleeding, major bleeding, thrombosis, all-cause death, as well as composite endpoints and found that BMI was a protective factor for major bleeding, total bleeding, all-cause death, and composite endpoints, which is consistent with the results of our previous study [36]. Higher BMI was associated with lower major bleeding, total bleeding, and better survival. Our study identified combined heart failure and vascular disease risk factors for a composite endpoint in patients with NVAF. In contrast, Ding's study found a poorer prognosis in patients with greater age, decreased renal function, diabetes, coronary artery disease, heart failure, prior thromboembolism, prior bleeding, peripheral arterial disease, chronic obstructive pulmonary disease, and treatment with antiplatelet agents, digoxin, and diuretics. The inconsistent risk factors may be due to (1) the different populations included. Ding et al. [34] All patients newly diagnosed with AF (<3 months before the baseline visit) were from multiple countries. However, the present study is a multicenter retrospective study in China and does not define the time to diagnose NVAF. (2) Different confounding factors that may impact the analysis results were incorporated.

We performed separate subgroup analyses for patients in the RFA and no RFA groups. All-cause death among patients who underwent RFA was significantly lower in patients with dabigatran compared with rivaroxaban. In contrast, major bleeding, total bleeding, and composite endpoints were significantly lower in patients with rivaroxaban compared to dabigatran in the no RFA group. This suggests that in patients with NVAF undergoing RFA, postoperative use of dabigatran or rivaroxaban has similar efficacy, but there is a better survival benefit with dabigatran. However, patients with NVAF without RFA appear to benefit more from rivaroxaban. There is growing evidence that RFA is beneficial for the prognosis of patients with NVAF and that ablation should be considered early in AF, as success rates decrease with treatment delay [37].

Our study is the first multicenter retrospective cohort analysis in China with a large sample size exploring the differences between major bleeding, total bleeding, thrombosis, all-cause death, and the composite endpoints of bleeding, thrombosis, and all-cause death in patients with and without RFA of NVAF using DOACs, with a large patient base covering the full age range. Also, our study has several limitations: (1) Due to the retrospective nature of this study, information on the results may be incomplete. (2) Due to the majority of elderly patients, it is difficult to avoid unclear or confusing memory during follow-up. (3) Adherence to prescribed DOACs was not assessed.

Conclusion

In patients with NVAF treated with DOACs, RFA was negatively associated with the risk of major bleeding, thrombosis, and the composite endpoint of bleeding, thrombosis, and all-cause death but was not associated with total bleeding or all-cause death. Patients with RFA of NVAF have a better prognosis with DOACs than those with NVAF without RFA.

Availability of data and materials

All data relevant to the study are included in the article as supplementary information.

Reference

  1. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, et al. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019;139:e56–528.

    Article  PubMed  Google Scholar 

  2. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64:e1-76.

    Article  PubMed  Google Scholar 

  3. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983–8.

    Article  CAS  PubMed  Google Scholar 

  4. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962.

    Article  PubMed  Google Scholar 

  5. Arbelo E, Brugada J, Hindricks G, Maggioni A, Tavazzi L, Vardas P, Anselme F, Inama G, Jais P, Kalarus Z, et al. ESC-EURObservational Research Programme: The Atrial Fibrillation Ablation Pilot Study, conducted by the European Heart Rhythm Association. Europace. 2012;14:1094–103.

    Article  PubMed  Google Scholar 

  6. Reddy VY, Dukkipati SR, Neuzil P, Natale A, Albenque JP, Kautzner J, Shah D, Michaud G, Wharton M, Harari D, et al. Randomized, Controlled Trial of the Safety and Effectiveness of a Contact Force-Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation: Results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) Study. Circulation. 2015;132:907–15.

    Article  PubMed  Google Scholar 

  7. Stabile G, Scaglione M, del Greco M, De Ponti R, Bongiorni MG, Zoppo F, Soldati E, Marazzi R, Marini M, Gaita F, et al. Reduced fluoroscopy exposure during ablation of atrial fibrillation using a novel electroanatomical navigation system: A multicentre experience. Europace. 2012;14:60–5.

    Article  PubMed  Google Scholar 

  8. McLellan AJ, Ling LH, Azzopardi S, Lee GA, Lee G, Kumar S, Wong MC, Walters TE, Lee JM, Looi KL, et al. A minimal or maximal ablation strategy to achieve pulmonary vein isolation for paroxysmal atrial fibrillation: A prospective multi-centre randomized controlled trial (the Minimax study). Eur Heart J. 2015;36:1812–21.

    Article  PubMed  Google Scholar 

  9. Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Weerasooriya R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015;372:1812–22.

    Article  PubMed  Google Scholar 

  10. Nery PB, Belliveau D, Nair GM, Bernick J, Redpath CJ, Szczotka A, Sadek MM, Green MS, Wells G, Birnie DH. Relationship Between Pulmonary V ein Reconnection and Atrial Fibrillation Recurrence: A Systematic Review and Meta-Analysis. JACC Clin Electrophysiol. 2016;2:474–83.

    Article  PubMed  Google Scholar 

  11. Knight BP. Anticoagulation for atrial fibrillation ablation – what is the optimal strategy? J Am Coll Cardiol. 2012;59:1175–7.

    Article  PubMed  Google Scholar 

  12. Heeger CH, Rillig A, Geisler D, Wohlmuth P, Fink T, Mathew S, et al. Left atrial appendage isolation in patients not responding to pulmonary vein isolation. Circulation. 2019;139(5):712–5.

    Article  PubMed  Google Scholar 

  13. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021;42:373–498.

    Article  PubMed  Google Scholar 

  14. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3:32–8.

    Article  PubMed  Google Scholar 

  15. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non- vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39:1330–93.

    Article  CAS  PubMed  Google Scholar 

  16. Nakamura R, Okishige K, Shigeta T, Nishimura T, Kurabayashi M, Yamauchi Y, et al. Clinical comparative study regarding interrupted and uninterrupted dabigatran therapy during perioperative periods of cryoballoon ablation for paroxysmal atrial fibrillation. J Cardiol. 2019;74:150–5.

    Article  PubMed  Google Scholar 

  17. Di Biase L, Burkhardt JD, Santangeli P, Mohanty P, Sanchez JE, Horton R, et al. Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the role of coumadin in preventing thromboembolism in atrial fibrillation (AF) patients undergoing catheter ablation (COMPARE) randomized trial. Circulation. 2014;129(25):2638–44.

    Article  PubMed  Google Scholar 

  18. Lakkireddy D, Reddy YM, Di Biase L, Vallakati A, Mansour MC, Santangeli P, et al. Feasibility and safety of uninterrupted rivaroxaban for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol. 2014;63(10):982–8.

    Article  CAS  PubMed  Google Scholar 

  19. Di Biase L, Lakkireddy D, Trivedi C, Deneke T, Martinek M, Mohanty S, et al. Feasibility and safety of uninterrupted periprocedural apixaban administration in patients undergoing radiofrequency catheter ablation for atrial fibrillation: results from a multicenter study. Heart Rhythm. 2015;12:1162–8.

    Article  PubMed  Google Scholar 

  20. Lakkireddy D, Reddy YM, Di Biase L, Vanga SR, Santangeli P, Swarup V, et al. Feasibility and safety of dabigatran versus warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol. 2012;59(13):1168–74.

    Article  CAS  PubMed  Google Scholar 

  21. Inoue K, Hirao K, Kumagai K, Kimura M, Miyauchi Y, Tsushima E, Ohishi M, Kimura K, Yasaka M, Yamaji H, Okawa K, Fujimoto M, Morishima I, Mine T, Shimizu W, Ohe M, Okumura K, JACRE Investigators. Long-term efficacy and safety of anticoagulation after atrial fibrillation ablation: data from the JACRE registry. J Cardiol. 2021;77(3):263–70.

    Article  PubMed  Google Scholar 

  22. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263–72.

    Article  PubMed  Google Scholar 

  23. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093–100. https://doi.org/10.1378/chest.10-0134. Epub 2010 Mar 18 PMID: 20299623.

    Article  PubMed  Google Scholar 

  24. Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in nonsurgical patients. J Thromb Haemost. 2005;3:692–4.

    Article  CAS  PubMed  Google Scholar 

  25. Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T, Streiff MB, Garcia DA, Liebman HA, Belani CP, O’Reilly EM, Patel JN, Yimer HA, Wildgoose P, Burton P, Vijapurkar U, Kaul S, Eikelboom J, McBane R, Bauer KA, Kuderer NM, Lyman GH, CASSINI Investigators. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med. 2019;380(8):720–8.

    Article  CAS  PubMed  Google Scholar 

  26. Wang SV, Schneeweiss S, Rassen JA. Optimal matching ratios in drug safety surveillance. Epidemiology. 2014;25(5):772–3.

    Article  PubMed  Google Scholar 

  27. Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33(7):1242–58.

    Article  PubMed  Google Scholar 

  28. Shi L-Z, Heng R, Liu S-M, Leng F-Y. Effect of catheter ablation versus antiarrhythmic drugs on atrial fibrillation: a meta-analysis of randomized controlled trials. Exp Ther Med. 2015;10:816–22.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Saglietto A, De Ponti R, Di Biase L, et al. Impact of atrial fibrillation catheter ablation on mortality, stroke, and heart failure hospitalizations: a meta-analysis. J Cardiovasc Electrophysiol. 2020;31:1040–7.

    Article  PubMed  Google Scholar 

  30. Mansour M, Heist EK, Agarwal R, Bunch TJ, Karst E, Ruskin JN, Mahapatra S. Stroke and Cardiovascular Events After Ablation or Antiarrhythmic Drugs for Treatment of Patients With Atrial Fibrillation. Am J Cardiol. 2018;121(10):1192–9.

    Article  PubMed  Google Scholar 

  31. Srivatsa UN, Danielsen B, Amsterdam EA, Pezeshkian N, Yang Y, Nordsieck E, Fan D, Chiamvimonvat N, White RH. CAABL-AF (California Study of Ablation for Atrial Fibrillation): Mortality and Stroke, 2005 to 2013. Circ Arrhythm Electrophysiol. 2018;11(6):e005739.

    Article  PubMed  Google Scholar 

  32. Saliba W, Schliamser JE, Lavi I, et al. Catheter ablation of atrial fibrillation is associated with reduced risk of stroke and mortality: a propensity score-matched analysis. Hear Rhythm. 2017;14:635–42.

    Article  Google Scholar 

  33. Kim M, Yu HT, Kim J, Kim TH, Uhm JS, Joung B, Lee MH, Pak HN. Atrial fibrillation and the risk of ischaemic strokes or intracranial haemorrhages: comparisons of the catheter ablation, medical therapy, and non-atrial fibrillation population. Europace. 2021;23(4):529–38.

    Article  PubMed  Google Scholar 

  34. Ding WY, Calvert P, Gupta D, Huisman MV, Lip GYH, GLORIA-AF Investigators. Impact of early ablation of atrial fibrillation on long-term outcomes: results from phase II/III of the GLORIA-AF registry. Clin Res Cardiol. 2022;111(9):1057–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Niespialowska-Steuden M, Markides V, Farag M, et al. Catheter ablation for AF improves global thrombotic profile and enhances fibrinolysis. J Thromb Thrombolysis. 2017;44(4):413–26.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wu S, Huang N, Chen X, Jiang S, Zhang W, Hu W, Su J, Dai H, Gu P, Huang X, Du X, Li R, Zheng Q, Lin X, Zhang Y, Zou L, Liu Y, Zhang M, Liu X, Zhu Z, Sun J, Hong S, She W, Zhang J. Association between Body Mass Index and Clinical Outcomes in Patients with Non-valvular Atrial Fibrillation Receiving Direct Oral Anticoagulants: A New Piece of Evidence on the Obesity Paradox from China. Cardiovasc Drugs Ther. 2022 Apr 8.

  37. Chew DS, Black-Maier E, Loring Z, et al. Diagnosis-to-ablation time and recurrence of atrial fibrillation following catheter ablation: a systematic review and meta-analysis of observational studies. Circ Arrhythm Electrophysiol. 2020;13:e008128.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

All the authors are grateful to Meina Lv, Shaojun Jiang and Tingting Wu for their contribution to the data collation.

Funding

No specific funding was necessary for the conduct of this study.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, #18 Daoshan Road, Fuzhou, 350001, China

    Shuyi Wu, Chengfu Guan, Wenlin Xu & Jinhua Zhang

  2. Department of Cardiology, Fujian Medical University Union Hospital, Fujian, 350001, China

    Feilong Zhang

  3. Department of Pharmacy, Taikang Tongji(Wuhan) Hospital, Wuhan, 430000, China

    Nianxu Huang

  4. Department of Pharmacy, Fuling Hospital of Chongqing University, Chongqing, 408099, China

    Xia Chen

  5. Department of Pharmacy, The First People’s Hospital of Changde City, Hunan, 415000, China

    Wang Zhang

  6. Department of Pharmacy, Xinyang Central Hospital, Xinyang Hospital Affiliated to Zhengzhou University, Henan, 464000, China

    Wei Hu

  7. Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Anhui, 233004, China

    Jun Su

  8. Department of Pharmacy, Affiliated Fuzhou First Hospital of Fujian Medical University, Fujian, 350009, China

    Hengfen Dai

  9. Department of Pharmacy, Suining Central Hospital, Suining, 629000, Sichuan, China

    Ping Gu

  10. Department of Pharmacy, Zhangzhou Affiliated Hospital of Fujian Medical University, Fujian, 363000, China

    Xiaohong Huang

  11. Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Xiaoming Du

  12. Department of Pharmacy, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Shanxi, 030032, China

    Ruijuan Li

  13. Department of Pharmacy, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Qiaowei Zheng

  14. Department of Pharmacy, Pingtan County General Laboratory Area Hospital, Fujian, 350400, China

    Xiangsheng Lin

  15. Department of Pharmacy, The First Affiliated Hospital of Jiamusi University, Heilongjiang, 154002, China

    Yanxia Zhang

  16. Department of Pharmacy, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, China

    Lang Zou

  17. Department of Pharmacy, Huaihe Hospital of Henan University, Henan, 475000, China

    Yuxin Liu

  18. Department of Pharmacy, Affiliated Qingdao Third People’s Hospital, Qingdao University, Shandong, 266041, China

    Min Zhang

  19. Department of Pharmacy, of People’s Hospital He’nan University of Chinese Medicine (People’s Hospital of Zhengzhou), Zhengzhou, 450003, China

    Xiumei Liu

  20. Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Jiangsu, 215004, China

    Zhu Zhu

  21. Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, Inner Mongolia, China

    Jianjun Sun

  22. Department of Pharmacy, Quanzhou First Hospital, Fujian, 362000, China

    Shanshan Hong

  23. Department of Medical Administration, Dongguan Kanghua Hospital, Guangdong, 523000, China

    Weibin She

Authors
  1. Shuyi Wu
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  2. Chengfu Guan
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  3. Wenlin Xu
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  4. Feilong Zhang
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  5. Nianxu Huang
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  6. Xia Chen
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  7. Wang Zhang
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  9. Jun Su
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  18. Lang Zou
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  20. Min Zhang
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  25. Weibin She
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  26. Jinhua Zhang
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Contributions

JZ initiated the study. JZ, FZ, XC, NH, HD, WZ, XH, PG, XL, XD, QZ, YL, XL, RL, MZ, and ZZ collected and entered the data. CG and WX performed data collation. SW and JZ performed data extraction and analyses. SW drafted the first version of the manuscript. JZ ,SW, CG, WX, NH and FZ critically reviewed the manuscript and revised it. SW, FZ, JS, and YZ worked on data validation. LZ, JS, SH, WS performed the graphical revisions. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jinhua Zhang.

Ethics declarations

Ethics approval and consent to participate

The study complies with the Declaration of Helsinki and was authorized by The Ethics Committee of Fujian Medical University Union Hospital.

Consent for publication

The requirement for patient consent was waived due to its retrospective nature.

Competing interests

The authors declare no competing interests.

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Supplementary Information

Additional file1:

Table 1. List of 15 multi-center hospitals, Table 2. Baseline characteristics after propensity score matching, Table 3. Baseline characteristics of patients with NVAF in the RFA group taking rivaroxaban and dabigatran before and after matching, Table 4. Clinical Outcomes of DOACs in NVAF patients with RFA after propensity score matching, Table 5. Baseline characteristics of patients with NVAF in the no RFA group taking rivaroxaban and dabigatran before and after matching, Table 6. Clinical Outcomes of DOACs in NVAF patients with no RFA after propensity score matching, Fig. 1. Sub-center Distribution Map, Fig. 2. Association of the RFA and Potential Risk Factors with Total Bleeding in NVAF Patients, Fig. 3. Association of the RFA and Potential Risk Factors with Major Bleeding in NVAF Patients, Fig. 4. Association of the RFA and Potential Risk Factors with Thrombosis in NVAF Patients, Fig. 5. Association of the RFA and Potential Risk Factors with All-caused Deaths in NVAF Patients, Fig. 6. Association of the RFA and Potential Risk Factors with Composite outcome in NVAF Patients.

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Wu, S., Guan, C., Xu, W. et al. Safety and efficacy of direct oral anticoagulation in patients with and without radiofrequency ablation of non-valvular atrial fibrillation: a multicenter retrospective cohort study. Thrombosis J 21, 37 (2023). https://doi.org/10.1186/s12959-023-00483-6

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Keywords

Thrombosis Journal

ISSN: 1477-9560

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