What Surgeons Should Know About Non-Vitamin K Oral Anticoagulants: A Review

JAMA Surg. 2018 Jun 1;153(6):577-585. doi: 10.1001/jamasurg.2018.0374.

Abstract

Importance: Non-vitamin K oral anticoagulants (NOACs) are increasingly prescribed for patients to treat or prevent arterial or venous thromboembolism. The following 4 NOAC agents are approved by the US Food and Drug Administration for clinical use: dabigatran etexilate, apixaban, edoxaban tosylate, and rivaroxaban. A good understanding of these agents' pharmacologic properties is important for surgeons given their marked differences compared with warfarin sodium. This review highlights key practical issues surrounding the use of NOACs in the perioperative setting.

Observations: The PubMed and Cochrane Library databases were searched for English-language studies from May 1, 2009, until May 1, 2017, for randomized clinical trials, meta-analyses, systematic reviews, observational studies, and clinical guidelines. From a systematic review of the published literature that included 70 articles and 166 404 patients, this study identified 5 key practical issues surrounding the use of NOACs in the perioperative setting. These include patient populations for which NOAC use is indicated and contraindicated, the timing of NOAC treatment cessation before invasive interventions, management of NOAC-treated patients requiring urgent interventions, the need for "bridging," and the timing of NOAC treatment's reinitiation after invasive interventions. Important findings are as follows: NOAC agents are not recommended for patients with mechanical heart valves or advanced kidney disease (creatinine clearance, <15 mL/min); minimal to no anticoagulant effect remains when therapy with a NOAC is withheld for 48 to 72 hours before surgery in the context of normal kidney function; a reversal agent is clinically available for dabigatran, while reversal agents for apixaban, edoxaban, and rivaroxaban are under regulatory review; and laboratory testing of the anticoagulant effects of NOACs are not routinely available. There is a paucity of high-quality data on the optimal timing of NOAC cessation and resumption in the perioperative period, particularly for patients who undergo procedures with high bleeding risk.

Conclusions and relevance: The anticoagulant effect of NOAC agents is predictable but not readily measurable in routine clinical practice. A number of uncertainties remain surrounding the use of these agents in the perioperative setting. Ongoing prospective studies and randomized clinical trials will provide greater clarity on these management issues in the near future.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Clinical Competence*
  • Humans
  • Surgeons / standards*
  • Thromboembolism / etiology
  • Thromboembolism / prevention & control*
  • Vitamin K

Substances

  • Anticoagulants
  • Vitamin K