Lead Investigator: Akira Kimata, University of Tsukuba
Title of Research Proposal: Optimal interruption time of dabigatran per OS to Ablation (O-A time) in patients with atrial fibrillation Integrated analysis of 2 randomized controlled clinical trials.
Vivli Data Request: 4036
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Catheter ablation of atrial fibrillation (AF) is a well-established treatment. The most important complications associated with ablation of AF are thromboembolic events (stroke or transient ischemic attack) and bleeding events. Systemic anticoagulation before, during, and after ablation is important for the reduction of these risks. Recently, instead of conventional anticoagulants such as warfarin, direct oral anticoagulants (DOACs) have been used for the prevention of thromboembolic events in patients with AF. However, data assessing the safety and efficacy of anticoagulation therapy with DOACs during ablation of AF are limited.
RE-CIRCUIT (listed in Vivli database, NCT02348723) and ABRIDGE-J (our data, UMIN000013129) are recently published clinical studies showing that anticoagulation therapy with dabigatran (a DOAC) was associated with fewer complications compared with warfarin therapy. The dabigatran administration protocols prior to ablation were slightly different in the 2 studies. Therefore, the aim of this study was to clarify the optimal administration protocol of dabigatran prior to ablation by integrated analysis of the 2 studies.
Statistical Analysis Plan:
We selected the 2 studies because that RE-CIRCUIT and ABRIDGE-J are the only 2 prospective, randomized, open-label, multicenter, controlled studies that evaluated the safety and efficacy of dabigatran during the perioperative period of AF ablation. Included patients were aged ≥18 years (RE-CIRCUIT) or 20 to 85 years (ABRIDGE-J); diagnosed with paroxysmal or persistent non-valvular AF, planned ablation of AF, and were eligible for treatment with dabigatran according to local prescribing information. With regards to evaluation of the O-A time, only 8 participants are missing the data of administration time of dabigatran, according to RE-CIRCUIT study. With regards to major bleeding, the primary endpoint of this integrated analysis, the same ISTH definition was used in both studies.
We will perform an integrated summary of effectiveness (ISE) using the 2 studies, which is also called as an individual patient data (IPD) meta-analysis. Primary and secondary endpoints will be compared between groups. For each endpoint, the incidence of the event for each group and its odds ratios and 95% CI will be calculated. The chi-square test (>5 events) and Fisher exact test (<5 events) will be performed for intergroup comparison of the incidence. Time-to-event analysis will be performed using the Kaplan-Meier estimate, and the log-rank test will be used to determine between-group differences. A 2-sided p value of <0.05 will be considered statistically significant.
Sponsor: Boehringer Ingelheim
Study ID: NCT02348723
Sponsor ID: 1160.204
The title is “Safety and efficacy of minimally interrupted dabigatran vs uninterrupted warfarin therapy in adults undergoing atrial fibrillation catheter ablation: A randomized clinical trial (ABRIDGE-J)” This study showed that minimally interrupted dabigatran (1-2 doses were put on hold before ablation) was associated with a significantly lower rate of major bleeding events compared with uninterrupted warfarin, and did not increase thromboembolic events (n = 220 in the dabigatran group and n = 222 in the warfarin group). Published: April 19, 2019. Doi:10.1001/jamanetworkopen.2019.1994 Corresponding author: KazutakaAonuma, MD, PhD, Department of Cardiology, Faculty of Medicine, University of Tsukuba. Funding/Support: The study was supported by grants from Boehringer Ingelheim.
Study ID: umin.ac.jp Identifier: UMIN000013129
- Circulation. Late-Breaking Science Abstracts and Featured Science Abstracts From the American Heart Association’s Scientific Sessions 2019 and Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2019, Volume: 140, Issue: 25, Pages: e965-e1011, DOI: (10.1161/CIR.0000000000000742) https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000742
- Akira Kimata, Akihiko Nogami, Hiro Yamasaki, Tomohiro Ohigashi, Masahiko Gosho, Miyako Igarashi, Yukio Sekiguchi, Masaki Ieda, Hugh Calkins, Kazutaka Aonuma, Optimal interruption time of dabigatran oral administration to ablation (O-A time) in patients with atrial fibrillation: Integrated analysis of 2 randomized controlled clinical trials, Journal of Cardiology, 2021, ISSN 0914-5087, doi: 10.1016/j.jjcc.2020.12.010.