Interrupted versus uninterrupted anticoagulation therapy for catheter ablation in adults with arrhythmias

Abstract

Background: The management of anticoagulation therapy around the time of catheter ablation (CA) procedure for adults with arrhythmia is critical and yet is variable in clinical practice. The ideal approach for safe and effective perioperative management should balance the risk of bleeding during uninterrupted anticoagulation while minimising the risk of thromboembolic events with interrupted therapy. Objectives: To compare the efficacy and harms of interrupted versus uninterrupted anticoagulation therapy for catheter ablation (CA) in adults with arrhythmias. Search methods: We searched CENTRAL, MEDLINE, Embase, and SCI-Expanded on the Web of Science for randomised controlled trials on 5 January 2021. We also searched three registers on 29 May 2021 to identify ongoing or unpublished trials. We performed backward and forward searches on reference lists of included trials and other systematic reviews and contacted experts in the field. We applied no restrictions on language or publication status. Selection criteria: We included randomised controlled trials comparing uninterrupted anticoagulation with any modality of interruption with or without heparin bridging for CA in adults aged 18 years or older with arrhythmia. Data collection and analysis: Two review authors conducted independent screening, data extraction, and assessment of risk of bias. A third review author resolved disagreements. We extracted data on study population, interruption strategy, ablation procedure, thromboembolic events (stroke or systemic embolism), major and minor bleeding, asymptomatic thromboembolic events, cardiovascular and all-cause mortality, quality of life (QoL), length of hospital stay, cost, and source of funding. We used GRADE to assess the certainty of the evidence. Main results: We identified 12 studies (4714 participants) that compared uninterrupted periprocedural anticoagulation with interrupted anticoagulation. Studies performed an interruption strategy by either a complete interruption (one study) or by a minimal interruption (11 studies), of which a single-dose skipped strategy was used (nine studies) or two-dose skipped strategy (two studies), with or without heparin bridging. Studies included participants with a mean age of 65 years or greater, with only two studies conducted in relatively younger individuals (mean age less than 60 years). Paroxysmal atrial fibrillation (AF) was the primary type of AF in all studies, and seven studies included other types of AF (persistent and long-standing persistent). Most participants had CHADS2 or CHADS2-VASc demonstrating a low–moderate risk of stroke, with almost all participants having normal or mildly reduced renal function. Ablation source using radiofrequency energy was the most common (seven studies). Ten studies (2835 participants) were conducted in East Asian countries (Japan, China, and South Korea), while the remaining two studies were conducted in the USA. Eight studies were conducted in a single centre. Postablation follow-up was variable among studies at less than 30 days (three studies), 30 days (six studies), and more than 30 days postablation (three studies). Overall, the meta-analysis showed high uncertainty of the effect between the interrupted strategy compared to uninterrupted strategy on the primary outcomes of thromboembolic events (risk ratio (RR) 1.76, 95% confidence interval (CI) 0.33 to 9.46; I2 = 59%; 6 studies, 3468 participants; very low-certainty evidence). However, subgroup analysis showed that uninterrupted vitamin A antagonist (VKA) is associated with a lower risk of thromboembolic events without increasing the risk of bleeding. There is also uncertainty on the outcome of major bleeding events (RR 1.10, 95% CI 0.59 to 2.05; I2= 6%; 10 studies, 4584 participants; low-certainty evidence). The uncertainty was also evident for the secondary outcomes of minor bleeding (RR 1.01, 95% CI 0.46 to 2.22; I2 = 87%; 9 studies, 3843 participants; very low-certainty evidence), all-cause mortality (RR 0.34, 95% CI 0.01 to 8.21; 442 participants; low-certainty evidence) and asymptomatic thromboembolic events (RR 1.45, 95% CI 0.85 to 2.47; I2 = 56%; 6 studies, 1268 participants; very low-certainty evidence). There was a lower risk of the composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality) in the interrupted compared to uninterrupted arm (RR 0.23, 95% CI 0.07 to 0.81; 1 study, 442 participants; low-certainty evidence). In general, the low event rates, different comparator anticoagulants, and use of different ablation procedures may be the cause of imprecision and heterogeneity observed. Authors' conclusions: This meta-analysis showed that the evidence is uncertain to inform the decision to either interrupt or continue anticoagulation therapy around CA procedure in adults with arrhythmia on outcomes of thromboembolic events, major and minor bleeding, all-cause mortality, asymptomatic thromboembolic events, and a composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality). Most studies in the review adopted a minimal interruption strategy which has the advantage of reducing the risk of bleeding while maintaining a lower level of anticoagulation to prevent periprocedural thromboembolism, hence low event rates on the primary outcomes of thromboembolism and bleeding. The one study that adopted a complete interruption of VKA showed that uninterrupted VKA reduces the risk of thromboembolism without increasing the risk of bleeding. Hence, future trials with larger samples, tailored to a more generalisable population and using homogeneous periprocedural anticoagulant therapy and ablation source are required to address the safety and efficacy of the optimal management of anticoagulant therapy prior to ablation.