Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 14;43(47):4899-4908.
doi: 10.1093/eurheartj/ehac587.

Bleeding and ischaemic events after first bleed in anticoagulated atrial fibrillation patients: risk and timing

Pascal B Meyre  1   2 , Steffen Blum  1   2 , Elisa Hennings  1   2 , Stefanie Aeschbacher  1   2 , Tobias Reichlin  3 , Nicolas Rodondi  4   5 , Jürg H Beer  6 , Annina Stauber  7 , Andreas Müller  7 , Tim Sinnecker  8   9 , Elisavet Moutzouri  4   5 , Rebecca E Paladini  1   2 , Giorgio Moschovitis  10 , Giulio Conte  11 , Angelo Auricchio  11 , Alexandra Ramadani  1   2 , Matthias Schwenkglenks  12   13 , Leo H Bonati  8 , Michael Kühne  1   2 , Stefan Osswald  1   2 , David Conen  14
Affiliations
Free article

Bleeding and ischaemic events after first bleed in anticoagulated atrial fibrillation patients: risk and timing

Pascal B Meyre et al. Eur Heart J. .
Free article

Abstract

Aims: To determine the risk of subsequent adverse clinical outcomes in anticoagulated patients with atrial fibrillation (AF) who experienced a new bleeding event.

Methods and results: Anticoagulated AF patients were followed in two prospective cohort studies. Information on incident bleeding was systematically collected during yearly follow-up visits and events were adjudicated as major bleeding or clinically relevant non-major bleeding (CRNMB) according to the International Society on Thrombosis and Haemostasis guidelines. The primary outcome was a composite of stroke, myocardial infarction (MI), or all-cause death. Time-updated multivariable Cox proportional-hazards models were used to compare outcomes in patients with and without incident bleeding. Median follow-up was 4.08 years [interquartile range (IQR): 2.93-5.98]. Of the 3277 patients included (mean age 72 years, 28.5% women), 646 (19.7%) developed a new bleeding, 297 (9.1%) a major bleeding and 418 (12.8%) a CRNMB. The incidence of the primary outcome was 7.08 and 4.04 per 100 patient-years in patients with and without any bleeding [adjusted hazard ratio (aHR): 1.36, 95% confidence interval (CI): 1.16-1.61; P < 0.001; median time between a new bleeding and a primary outcome 306 days (IQR: 23-832)]. Recurrent bleeding occurred in 126 patients [incidence, 8.65 per 100 patient-years (95% CI: 7.26-10.30)]. In patients with and without a major bleeding, the incidence of the primary outcome was 11.00 and 4.06 per 100 patient-years [aHR: 2.04, 95% CI: 1.69-2.46; P < 0.001; median time to a primary outcome 142 days (IQR: 9-518)], and 59 had recurrent bleeding [11.61 per 100 patient-years (95% CI: 8.99-14.98)]. The incidence of the primary outcome was 5.29 and 4.55 in patients with and without CRNMB [aHR: 0.94, 95% CI: 0.76-1.15; P = 0.53; median time to a composite outcome 505 days (IQR: 153-1079)], and 87 had recurrent bleeding [8.43 per 100 patient-years (95% CI: 6.83-10.40)]. Patients who had their oral anticoagulation (OAC) discontinued after their first bleeding episode had a higher incidence of the primary composite than those who continued OAC (63/89 vs. 159/557 patients; aHR: 4.46, 95% CI: 3.16-6.31; P < 0.001).

Conclusion: In anticoagulated AF patients, major bleeding but not CRNMB was associated with a high risk of adverse outcomes, part of which may be explained by OAC discontinuation. Most events occurred late after the bleeding episode, emphasizing the importance of long-term follow-up in these patients.

Keywords: Atrial fibrillation; bleeding; death; oral anticoagulation; outcomes; stroke.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: S.B. received funding from the Swiss National Science Foundation, the Mach-Gaensslen Foundation and the Bangerter-Rhyner Foundation outside the submitted work. T.R. reports research grants from the Swiss National Science Foundation, the Swiss Heart Foundation and the sitem insel support fund, all for work outside the submitted study; speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense Webster, Biotronik, Boston Scientific, Daiichi Sankyo, Medtronic, Pfizer-BMS and Roche, all for work outside the submitted study; support for his institution’s fellowship programme from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific and Medtronic for work outside the submitted study. A.M. reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical, and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St. Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, and consultant honoraria for Biosense Webster, Medtronic, Abbott/St. Jude Medcal, and Biotronik. M.S. reports grants via employment institution from Amgen, Bristol Myers & Squibb, Merck Sharp and Dohme, Novartis, Pfizer; personal fees from Amgen, Bristol Myers & Squibb, Sandoz, all outside of the current work. G.M. has received consultant fees for taking part to advisory boards from Novartis, Boehringer Ingelheim, Bayer, Astra Zeneca and Daiichi Sankyo, all outside of the current work. M.K. reports personal fees from Bayer, Böhringer Ingelheim, Pfizer-BMS, Daiichi Sankyo, Medtronic, Biotronik, Boston Scientific, Johnson&Johnson; grants from Bayer, Pfizer, Boston Scientific, BMS, Biotronik; grants from the Swiss National Science Foundation (Grant numbers 33CS30_148474, 33CS30_177520, 32473B_176178), the Swiss Heart Foundation, the Foundation for Cardiovascular Research Basel and the University of Basel. D.C. has received consultant fees from Roche Diagnostics; and speaker fees from Servier and BMS/Pfizer, all outside of the current work. The remaining authors have nothing to disclose.

Comment in

Publication types