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Safety of Anticoagulation Interruption in Patients Undergoing Surgery or Invasive Procedures: A Systematic Review and Meta-analyses of Randomized Controlled Trials and Non-randomized Studies

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Abstract

Background

The safety of anticoagulation interruption in patients requiring surgical or invasive procedures remains unclear. We thus performed a systematic review and meta-analyses of randomized controlled trials (RCTs) and non-randomized studies (NRS).

Methods

MEDLINE, Embase and Central databases were searched to March 2017 without date or language restrictions. We considered RCTs and NRS comparing anticoagulation interruption with any anticoagulation (continuation or heparin bridging) in adult surgical patients taking oral anticoagulation. Data were independently extracted. The quality of the evidence was assessed following recommendations from the Cochrane collaboration (GRADE approach). Risk ratios were calculated for 30-day events: thromboembolic (TE) events, major bleeding and mortality. Additional analyses explored the effects of different anticoagulation strategies.

Results

Twelve reports were included: 4 RCTs (2190 participants) and 8 NRS (18993 participants). Trials included mostly participants with atrial fibrillation. Interrupting anticoagulation did not seem to increase TE events (RR 0.65, 95% CI [0.33, 1.30]—4 studies, 2190 participants) and resulted in less bleeding (RR 0.41, 95% CI [0.22, 0.78]—3 studies, 2126 participants) compared to anticoagulation continuation or heparin bridging. The GRADE assessment was moderate. Similar results were found in non-randomized studies, but the quality of the evidence was low. Possible strategy-specific effects were identified: forgoing heparin bridging seemed beneficial, but these effects were less clear with other strategies.

Conclusion

Interrupting anticoagulation in patients requiring invasive procedures did not seem to result in harm and protected against major bleeding. Uncertainty remains regarding the safety of this strategy in indications other than atrial fibrillation and in moderate- to high-risk surgery.

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Acknowledgements

This work was supported by institutional funds, Institute of Anesthesiology, University of Zurich and University Hospital of Zurich, Switzerland. The funding organization had no role in the design and conduct of the study; in the collection, management, analysis or interpretation of the data; or in the preparation, review or approval of the manuscript.

Author contributions

Hovaguimian and Spahn conceived and designed the study; Hovaguimian, Köppel and Spahn acquired, analyzed and interpreted the data; Hovaguimian drafted the manuscript; Hovaguimian, Köppel and Spahn critically revised the manuscript for important intellectual content; Hovaguimian performed statistical analysis; Spahn obtained the funding for the study; Hovaguimian provided administrative, technical and material support; Spahn supervised the study; Dr Hovaguimian had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Spahn affirms that this manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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Authors and Affiliations

  1. Institute of Anesthesiology, University of Zurich and University Hospital of Zurich, 8091, Zurich, Switzerland

    Frédérique Hovaguimian, Sabrina Köppel & Donat R. Spahn

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  1. Frédérique Hovaguimian
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  2. Sabrina Köppel
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  3. Donat R. Spahn
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Correspondence to Frédérique Hovaguimian.

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This article does not contain any studies with human participants performed by any of the authors.

Declaration of interest

Dr FH and Dr SK were supported by institutional funds during the realization of this work (institutional funds, Institute of Anesthesiology, University of Zurich and University Hospital of Zurich, Switzerland); Dr DRS reports that his academic department is/has been receiving grant support from the Swiss National Science Foundation, Berne, Switzerland, the Ministry of Health (Gesundheitsdirektion) of the Canton of Zurich, Switzerland, for Highly Specialized Medicine, the Swiss Society of Anesthesiology and Reanimation (SGAR), Berne, Switzerland, the Swiss Foundation for Anesthesia Research, Zurich, Switzerland, Bundesprogramm Chancengleichheit, Berne, Switzerland, CSL Behring, Berne, Switzerland, Vifor SA, Villars-sur-Glane, Switzerland. Prof DRS was the chair of the ABC Faculty and is the co-chair of the ABC-Trauma Faculty, which both are managed by Physicians World Europe GmbH, Mannheim, Germany, and sponsored by unrestricted educational grants from Novo Nordisk Health Care AG, Zurich, Switzerland, CSL Behring GmbH, Marburg, Germany, and LFB Biomedicaments, Courtaboeuf Cedex, France. In the past 5 years, Dr DRS has received honoraria or travel support for consulting or lecturing from the following companies: Abbott AG, Baar, Switzerland, AMGEN GmbH, Munich, Germany, AstraZeneca AG, Zug, Switzerland, Baxter AG, Volketswil, Switzerland, Baxter S.p.A., Roma, Italy, Bayer (Schweiz) AG, Zurich, Switzerland, Bayer Pharma AG, Berlin, Germany, B. Braun Melsungen AG, Melsungen, Germany, Boehringer lngelheim (Schweiz) GmbH, Basel, Switzerland, Bristol-Myers-Squibb, Rueil-Malmaison Cedex, France, and Baar, Switzerland, CSL Behring GmbH, Hattersheim am Main, Germany, and Berne, Switzerland, Curacyte AG, Munich, Germany, Daiichi Sankyo (Schweiz) AG, Thalwil, Switzerland, Ethicon Biosurgery, Sommerville, New Jersey, USA, Fresenius SE, Bad Homburg v.d.H., Germany, Galenica AG, Bern, Switzerland (including Vifor SA, Villars-sur-Glane, Switzerland), GlaxoSmithKline GmbH & Co. KG, Hamburg, Germany, Janssen-Cilag AG, Baar, Switzerland, Janssen-Cilag EMEA, Beerse, Belgium, LFB Biomedicaments, Courtaboeuf Cedex, France, Merck Sharp & Dahme AG, Luzern, Switzerland, Novo Nordisk A/S, Bagsvard, Denmark, Octapharma AG, Lachen, Switzerland, Organon AG, Pfaffikon/SZ, Switzerland, Oxygen Biotherapeutics, Costa Mesa, CA, PAION Deutschland GmbH, Aachen, Germany, Pharmacosmos A/S, Holbaek, Denmark, Photonics Healthcare B.V., Utrecht, Netherlands, ratiopharm Arzneimittel Vertriebs GmbH, Vienna, Austria, Roche Diagnostics International Ltd, Reinach, Switzerland, Roche Pharma (Schweiz) AG, Reinach, Switzerland, Sarstedt AG & Co., Sevelen, Switzerland, and Numbrecht, Germany, Schering-Plough International, Inc., Kenilworth, New Jersey, USA, Tern International GmbH, Munich, Germany, Verum Diagnostica GmbH, Munich, Germany, Vifor Pharma Deutschland GmbH, Munich, Germany, Vifor Pharma Osterreich GmbH, Vienna, Austria, Vifor (International) AG, St. Gallen, Switzerland.

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Hovaguimian, F., Köppel, S. & Spahn, D.R. Safety of Anticoagulation Interruption in Patients Undergoing Surgery or Invasive Procedures: A Systematic Review and Meta-analyses of Randomized Controlled Trials and Non-randomized Studies. World J Surg 41, 2444–2456 (2017). https://doi.org/10.1007/s00268-017-4072-x

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