Duration of Anticoagulation Interruption Before Invasive Procedures and Outcomes in Patients with Atrial Fibrillation: Insights from the ARISTOTLE Trial

HomeCirculationVol. 146, No. 12Duration of Anticoagulation Interruption Before Invasive Procedures and Outcomes in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBDuration of Anticoagulation Interruption Before Invasive Procedures and Outcomes in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial Sana M. Al-Khatib, Daniel M. Wojdyla, Christopher B. Granger, Lars Wallentin, David A. Garcia, Ziad Hijazi, Claes Held, John H. Alexander, Dragos Vinereanu, Gregory C. Flaker, Elaine M. Hylek and Renato D. Lopes Sana M. Al-KhatibSana M. Al-Khatib Correspondence to: Sana M. Al-Khatib, MD, MHS, Duke Clinical Research Institute, 300 Morgan St, Durham, NC 27701. Email E-mail Address: [email protected] https://orcid.org/0000-0002-3561-0146 Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.M.Al-K., D.M.W., C.B.G., J.H.A., R.D.L.). , Daniel M. WojdylaDaniel M. Wojdyla Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.M.Al-K., D.M.W., C.B.G., J.H.A., R.D.L.). , Christopher B. GrangerChristopher B. Granger https://orcid.org/0000-0002-0045-3291 Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.M.Al-K., D.M.W., C.B.G., J.H.A., R.D.L.). , Lars WallentinLars Wallentin Uppsala Clinical Research Center and the Department of Medical Sciences, Cardiology, Uppsala University, Sweden (L.W., Z.H., C.H.). , David A. GarciaDavid A. Garcia Hematology Division, University of Washington, Seattle (D.A.G.). , Ziad HijaziZiad Hijazi https://orcid.org/0000-0002-7420-743X Uppsala Clinical Research Center and the Department of Medical Sciences, Cardiology, Uppsala University, Sweden (L.W., Z.H., C.H.). , Claes HeldClaes Held https://orcid.org/0000-0001-9402-7404 Uppsala Clinical Research Center and the Department of Medical Sciences, Cardiology, Uppsala University, Sweden (L.W., Z.H., C.H.). , John H. AlexanderJohn H. Alexander https://orcid.org/0000-0002-1444-2462 Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.M.Al-K., D.M.W., C.B.G., J.H.A., R.D.L.). , Dragos VinereanuDragos Vinereanu https://orcid.org/0000-0002-9054-8779 University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania (D.V.). , Gregory C. FlakerGregory C. Flaker Division of Cardiology, University of Missouri, Columbia, MO (G.C.F.). , Elaine M. HylekElaine M. Hylek Boston University School of Medicine, Boston, MA (E.M.H.). and Renato D. LopesRenato D. Lopes https://orcid.org/0000-0003-2999-4961 Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.M.Al-K., D.M.W., C.B.G., J.H.A., R.D.L.). Originally published19 Sep 2022https://doi.org/10.1161/CIRCULATIONAHA.122.059438Circulation. 2022;146:958–960Factor Xa inhibitors are the predominant type of oral anticoagulant for stroke prevention in atrial fibrillation.1 Although recommendations exist on holding these medications before procedures with a low, intermediate, or high bleeding risk, whether and for how long to interrupt these medications around the time of a procedure continue to be debated.2In a previous analysis of the ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation), the 30-day postprocedure risk of stroke and major bleeding was similarly low in apixaban- and warfarin-treated patients, regardless of whether or not anticoagulation was interrupted at the time of a procedure.3 Despite these results, many clinicians remain concerned about the risk of stroke when anticoagulation is held and the risk of bleeding when anticoagulation is not held before an invasive procedure. We conducted this subanalysis to examine how the duration of anticoagulation interruption before an invasive procedure in patients with atrial fibrillation is associated with 30-day outcomes.This post hoc descriptive analysis included patients in ARISTOTLE who underwent an invasive procedure with a known procedure date (n=10 674).4 Procedures were not included if study medication was intermittently stopped and restarted in the 7 days before a procedure (n=204) or if no doses of study medication were taken for >7 days before a procedure (n=1210), because such interruptions were assumed not to be related to the procedure. We classified each procedure as "no interruption" (no interruption of study drug or if it was interrupted on the day of the procedure) or "interruption" (interruption 1–7 days before the procedure). Outcomes examined in this analysis include 30-day stroke or systemic embolism, myocardial infarction, all-cause death, major bleeding, a composite of major or clinically relevant nonmajor bleeding (per International Society on Thrombosis and Haemostasis criteria), and a net benefit end point of stroke, systemic embolism, or major bleeding. The study was approved by institutional review committees, and all patients provided informed consent.4 The data that support the findings of this study are available from the corresponding author on reasonable request.Of 18 201 patients enrolled in ARISTOTLE, 5439 (29.9%) had a procedure that met the criteria for this analysis, and 9260 procedures (3468 with no interruption and 5792 with interruption) were identified. Of these, 8994 were nonemergency procedures and 266 were emergency procedures. The most prevalent procedures were tooth extraction/oral surgery (14.6%), colonoscopy (9.9%), eye surgery (8.0%), upper gastrointestinal endoscopy (7.6%), and pacemaker implantation (3.5%). In 11.7% of the procedures, bridging with a parenteral anticoagulant was undertaken either before or after the procedure. In patients who interrupted study drug (n=5792), 38.1% were on study drug 1 day after the procedure, 57.8% were on it 2 days after the procedure, and 17.1% did not restart study drug within 8 days after the procedure. The number of patients stopping study drug 5 to 7 days before the procedure was slightly higher in the warfarin (25.1%) than in the apixaban group (19.1%), the remaining rates were similar between the 2 groups. The rates of stroke/systemic embolism, myocardial infarction, death and major bleeding were <0.5% for patients on study drug 1 or 2 days after the procedure. However, for patients who did not start study drug within 8 days from the procedure, the rates of stroke, myocardial infarction, death, and major bleeding were 1%, 0.8%, 1.3%, and 5.1%, respectively. The death rate ranged from 0.26% for a 3-day interruption to 3.94% for a 1-day interruption. The main results are shown in the Figure.Download figureDownload PowerPointFigure. Associations between the duration of apixaban and warfarin interruption before an invasive procedure in patients with atrial fibrillation and 30-day outcomes.The net benefit end point includes stroke/SE or major bleeding. CRNM indicates clinically relevant nonmajor; and SE, systemic embolism.In this analysis, the risk of stroke or systemic embolism was very low (2/2314; 0.086%) when anticoagulation (with apixaban or warfarin) was interrupted for up to 3 days before a procedure, a finding that is consistent with results from the PAUSE study (Perioperative Anticoagulation Use for Surgery Evaluation).5 The risk of stroke or systemic embolism in the present study increased to 0.61% if anticoagulation was interrupted for 5 days. Major bleeding varied from 1.10% for a 3-day interruption to 2.27% for a 1-day interruption. Although the numbers for 6-day and 7-day interruptions were small, the relatively higher rates of major bleeding in those subgroups likely reflect greater morbidity and higher use of bridging. The higher rate of death in the 1-day interruption group likely conveys the need for urgent procedures on acutely ill patients and major periprocedural bleeding.Our study's strengths include a large sample size and prospective and rigorous data. Key limitations are that the day of interruption before a procedure was not randomized, the number of patients in certain subgroups was too small to allow meaningful inferences, and with how data were collected, we could not discern if the study drug was interrupted for ≤2 consecutive doses. Also, decisions regarding interruption of anticoagulation in clinical practice where the type of anticoagulant is known are different from those made in the context of a double-blind, double-dummy clinical trial like ARISTOTLE.In conclusion, in the context of the ARISTOTLE trial, a 2- to 3-day interruption of apixaban appeared to be associated with the most favorable efficacy and safety profiles, including a low risk of stroke or systemic embolism and a low risk of major bleeding. This observation should be examined in future studies for further validation.Article InformationRegistration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00412984.Sources of FundingThe ARISTOTLE study (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) was funded by Bristol-Myers Squibb and Pfizer, Inc. Dr Al-Khatib has received research grants from the National Institutes of Health. Dr Granger received research grants from the Food and Drug Administration and consulting/speaker fees from the National Institutes of Health. Dr Hijazi received research support from the Swedish Society for Medical Research (S17-0133) and the Swedish Heart-Lung Foundation (20200722). Dr Held received research grants from Swedish Heart and Lung foundation. Dr Alexander received research grants from the Food and Drug Administration and the National Institutes of Health.Disclosures Dr Al-Khatib received research funding from Abbott, Medtronic and Boston Scientific. Dr Granger received research grants and consulting/speaker fees from Boehringer Ingelheim, Bristol-Myers Squibb, Janssen Pharmaceuticals, Pfizer, AstraZeneca, and Novartis; research grants from Daichii-Sankyo, AKROS, Apple, GlaxoSmithKline; and consulting/speaker fees from Bayer Corp, Boston Scientific Corp, Abbvie, Espero BioPharma, Medscape, Merck, NovoNordisk, Roche Diagnostics, Rho Diagnostics, Sirtex, and Verseon. Dr Wallentin received institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, Roche Diagnostics, Merck & Co; consulting fees from Abbott; holds 2 patents involving GDF-15 licensed to Roche Diagnostics (EP2047275B1 and US8951742B2). Dr Hijazi received research support from Uppsala University Hospital, Sweden; lecture and consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Roche Diagnostics. Dr Held: received institutional research grants from Pfizer; consulting fees from AstraZeneca, Boehringer Ingelheim, Bayer, and Coala Life. Dr Alexander received research grants from Bayer, Bristol-Myers Squibb, CryoLife, CSL Behring, Ferring, GlaxoSmithKline, Humacyte, XaTek; and consulting fees from AbbVie, Akros, Atricure, Bristol Myers Squibb, CryoLife, Ferring, Janssen, Pfizer, Portola Pharmaceuticals, VA Cooperative Studies. Dr Vinereanu received research grants and consulting/ speaker fees from Pfizer, Boehringer Ingelheim, Bayer, Novartis, and Amgen. Dr Hylek received research support from Abbott, Anthos Therapeutics, Bristol-Myers Squibb, CryoLife, Janssen, Medtronic; consulting fees from Bayer, Boston Scientific, Medtronic; and speaker fees from Boehringer Ingelheim and Pfizer. Dr Lopes received institutional research grants and consulting fees from Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and consulting fees from Amgen, Bayer, and Boehringer Ingelheim. The other authors report no conflicts.FootnotesCirculation is available at www.ahajournals.org/journal/circThis manuscript was sent to Paul Gurbel, Guest Editor, for review by expert referees, editorial decision, and final disposition.For Sources of Funding and Disclosures, see page 960.Correspondence to: Sana M. Al-Khatib, MD, MHS, Duke Clinical Research Institute, 300 Morgan St, Durham, NC 27701. Email [email protected]duke.eduReferences1. Luo N, Xu H, Jneid H, Fonarow GC, Lopes RD, Piccini JP, Curtis AB, Russo AM, Lewis WR, Matsouaka RA, et al. Use of oral anticoagulation in eligible patients discharged with heart failure and atrial fibrillation.Circ Heart Fail. 2018; 11:e005356. doi: 10.1161/CIRCHEARTFAILURE.118.005356LinkGoogle Scholar2. Doherty JU, Gluckman TJ, Hucker WJ, JanuzziOrtel JLTL, Saxonhouse SJ, Spinler SA. 2017 ACC expert consensus decision pathway for periprocedural management of anticoagulation in patients with nonvalvular atrial fibrillation: a report of the American College of Cardiology Clinical Expert Consensus Document Task Force.J Am Coll Cardiol. 2017; 69:871–898. doi: 10.1016/j.jacc.2016.11.024CrossrefMedlineGoogle Scholar3. Garcia D, Alexander JH, Wallentin L, Wojdyla DM, Thomas L, Hanna M, Al-Khatib SM, Dorian P, Ansell J, Commerford P, et al. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures.Blood. 2014; 124:3692–3698. doi: 10.1182/blood-2014-08-595496CrossrefMedlineGoogle Scholar4. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med. 2011; 365:981–992. doi: 10.1056/NEJMoa1107039CrossrefMedlineGoogle Scholar5. Douketis JD, Spyropoulos AC, Duncan J, Carrier M, Le Gal G, Tafur AJ, Vanassche T, Verhamme P, Shivakumar S, Gross PL, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant.JAMA Intern Med. 2019; 179:1469–1478. doi: 10.1001/jamainternmed.2019.2431CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Wang L, Zhang Y, Zhou W, Chen J, Li Y, Tang Q, Chen B, Zhang H, Zellmer L, Chen J, Chen Z, Li W, Liu X and Zhou H (2023) Relationship between left atrial appendage peak flow velocity and nonvalvular atrial fibrillation recurrence after cryoablation, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2023.1053102, 10 September 20, 2022Vol 146, Issue 12 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.122.059438PMID: 36121911 Originally publishedSeptember 19, 2022 Keywordsatrial fibrillationembolism, paradoxicalstrokehemorrhageapixabananticoagulantsPDF download Advertisement SubjectsAtrial Fibrillation