The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative
cardiac surgery atrial fibrillation is limited and mostly founded on clinical trials
that excluded this patient population. We performed a systematic review and meta-analysis
of clinical trials and observational studies to evaluate the hypothesis that DOACs
are safe compared to warfarin for the anticoagulation of patients with post-operative
cardiac surgery atrial fibrillation. We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov,
and the Cochrane Library for clinical trials and observational studies comparing DOAC
with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation.
Primary outcomes included stroke, systemic embolization, bleeding, and mortality.
We performed a random-effects meta-analysis of all outcomes. The meta-analysis for
the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies,
7143 patients, RR 0.64; 95% CI 0.50–0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization
(4 studies, 7289 patients, RR 0.64, 95% CI 0.41–1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95%
CI 0.74–1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI
0.74–1.37, I2: 26.5%). Current evidence suggests that DOACs, compared to warfarin, in the management
of atrial fibrillation after cardiac surgery is associated with lower risk of stroke
and a strong trend for lower risk of systemic embolization, and no evidence of increased
risk for hospital readmission, bleeding and mortality.
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Graphical Abstract
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REFERENCES
- Dabigatran versus warfarin in patients with atrial fibrillation [published correction appears in N Engl J Med. 2010 Nov 4;363(19):1877].N Engl J Med. 2009; 361: 1139-1151https://doi.org/10.1056/NEJMoa0905561
- Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.N Engl J Med. 2011; 365: 883-891https://doi.org/10.1056/NEJMoa1009638
- Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med. 2011; 365: 981-992https://doi.org/10.1056/NEJMoa1107039
- 2018 focused update of the canadian cardiovascular society guidelines for the management of atrial fibrillation.Can J Cardiol. 2018; 34: 1371-1392https://doi.org/10.1016/j.cjca.2018.08.026
- Clinical risk factors for postoperative atrial fibrillation among patients after cardiac surgery.Thorac Cardiovasc Surg. 2019; 67: 107-116https://doi.org/10.1055/s-0038-1667065
- Mechanisms, prevention, and treatment of atrial fibrillation after cardiac surgery.J Am Coll Cardiol. 2008; 51: 793-801https://doi.org/10.1016/j.jacc.2007.10.043
- Anticoagulation: american college of chest physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery.Chest. 2005; 128: 24S-27Shttps://doi.org/10.1378/chest.128.2_suppl.24s
- The management of atrial fibrillation after cardiac surgery.Heart. 2009; 95: 422-429https://doi.org/10.1136/hrt.2007.132795
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLOS Med. 2009; 6e1000097https://doi.org/10.1371/journal.pmed.1000097
- Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.JAMA. 2000; 283: 2008-2012https://doi.org/10.1001/jama.283.15.2008
- The society of thoracic surgeons 2018 adult cardiac surgery risk models: part 1-background, design considerations, and model development.Ann Thorac Surg. 2018; 105: 1411-1418https://doi.org/10.1016/j.athoracsur.2018.03.002
- The society of thoracic surgeons 2018 adult cardiac surgery risk models: part 2-statistical methods and results.Ann Thorac Surg. 2018; 105: 1419-1428https://doi.org/10.1016/j.athoracsur.2018.03.003
- Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC).Eur Heart J. 2010; 31: 2369-2429https://doi.org/10.1093/eurheartj/ehq278
- The HAS-BLED score for predicting major bleeding risk in anticoagulated patients with atrial fibrillation: a systematic review and meta-analysis.Clin Cardiol. 2015; 38: 555-561https://doi.org/10.1002/clc.22435
Higgins J.P.T., Altman D.G., Sterne J.A.C. Chapter 8: Assessing risk of bias in included studies. In: Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0.; 2011.
Wells G., Shea B., O'Connell D., Peterson J. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, ON: Ottawa Hospital Research Institute. Available from: URL: http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm. [cited 2021 June 23].
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188https://doi.org/10.1016/0197-2456(86)90046-2
- Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629LP-62634https://doi.org/10.1136/bmj.315.7109.629
- Oral anticoagulation post transcatheter aortic valve replacement in patients with atrial fibrillation.Circulation. 2017; 136 (Published 9 Jun 2018): A16378
- Novel oral anticoagulants vs warfarin for the management of postoperative atrial fibrillation: Clinical outcomes and cost analysis.Amer J Surg. 2015; 210: 1095-1103
- Non-vitamin K oral anticoagulant use after cardiac surgery is rapidly increasing.J Thorac and Cardiovasc Surg. 2019; 160: 1222-1231
- Vitamin K antagonists versus direct oral anticoagulants after transcatheter aortic valve implantation in atrial fibrillation.Eur Heart J Cardiovasc Pharmacother. 2019; https://doi.org/10.1093/ehjcvp/pvz064
- Edoxaban for the prevention of thromboembolism in patients with bioprosthetic valves in engage AF-TIMI 48.Circulation. 2017; 135: 1273-1275
- Dabigatran versus warfarin after bioprosthesis valve replacement for the management of atrial fibrillation postoperatively: DAWA pilot study.Drugs R D. 2016; 16: 149-154https://doi.org/10.1007/s40268-016-0124-1
- NOAC monotherapy in patients with concomitant indications for oral anticoagulation undergoing transcatheter aortic valve implantation.Clin Res Cardiol. 2018; 107: 799-806
- Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: Insights from the ARISTOTLE trial.Clin Cardiol. 2019; 42: 568-571
- Oral anticoagulant type and outcomes after transcatheter aortic valve replacement.J Amer Coll Cardiol: Cardiovasc Intervent. 2019; 12: 1566-1576
- Comparison of warfarin versus DOACs in patients with concomitant indication for oral anticoagulation undergoing TAVI; results from the ATLAS registry.J Thromb Thrombolysis. 2019; https://doi.org/10.1007/s11239-019-01968-w
- Anticoagulation choice after cardiac surgery: Are novel oral anticoagulants safe?.Circulation. 2018; 138: A10675
- Continued versus interrupted oral anticoagulation during transfemoral transcatheter aortic valve implantation and impact of postoperative anticoagulant management on outcome in patients with atrial fibrillation.Amer J Card. 2019; 123: 1134-1141
- Rivaroxaban vs warfarin for stroke prevention in patients with atrial fibrillation undergoing TAVR.Catheter Cardiovasc Interv. 2019; 93: S209-S210
- Clinical benefit of direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and bioprosthetic heart valves.Clin Ther. 2019; 41: 2549-2557https://doi.org/10.1016/j.clinthera.2019.10.008
- Apixaban in patients with atrial fibrillation after transfemoral aortic valve replacement.J Amer Coll Card - Cardiovascul Intervent. 2017; 10: 66-74
- Impact of novel oral anticoagulants vs warfarin on effusions after coronary artery bypass grafting.J Card Surg. 2019; 34: 419-423https://doi.org/10.1111/jocs.14054
Schünemann H., Brożek J., Guyatt G., Oxman A., editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013
- Atrial fibrillation after cardiac surgery: where are we now?.Indian Pacing Electrophysiol J. 2008; 8: 281-291
- Prevention, and treatment of atrial fibrillation after cardiac surgery.J Am Coll Cardiol. 2008; 51: 793-801https://doi.org/10.1016/j.jacc.2007.10.043
Part 10 prevention and treatment of atrial fibrillation following cardiac surgery. Accessed May 5, 2020. https://www.ccs.ca/eguidelines/Content/Topics/AtrialFib/Part%2010%20Prevention%20and%20Treatment%20of%20Atrial%20Fibrillation%20following%20Cardiac%20Surgery.htm
- Atrial fibrillation following cardiac surgery: risk analysis and long-term survival.J Cardiothorac Surg. 2012; 7: 87https://doi.org/10.1186/1749-8090-7-87
- Postoperative atrial fibrillation following cardiac surgery: a persistent complication.Eur J Cardiothorac Surg. 2017; 52: 665-672https://doi.org/10.1093/ejcts/ezx039
- Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med. 2011; 365: 981-992https://doi.org/10.1056/NEJMoa1107039
- Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009; 361: 1139-1151https://doi.org/10.1056/NEJMoa0905561
- Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.N Engl J Med. 2011; 365: 883-891https://doi.org/10.1056/NEJMoa1009638
- The systemic inflammatory response to cardiac surgery implications for the anesthesiologist.Anesthesiology. 2002; 97: 215-252
- Acute kidney injury following cardiac surgery: current understanding and future directions.Crit Care. 2016; 20https://doi.org/10.1186/s13054-016-1352-z
- Platelet counts, acute kidney injury, and mortality after coronary artery bypass grafting surgery.Anesthesiology. 2016; 124: 339-352https://doi.org/10.1097/ALN.0000000000000959
- Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive.J Thromb Haemost. 2010; 8: 30-36https://doi.org/10.1111/j.1538-7836.2009.03626.x
Article info
Publication history
Published online: June 07, 2021
Footnotes
Funding: No outside funding was used for this work.
Disclosures: MWC has received Speakers honoraria from Medtronic, Edwards Lifesciences and Terumo Aortic outside the submitted work.
Conflicts of Interest: None. Given the nature of our study, Institutional Research Board (IRB) waived the need for Informed Written Consent for Publication.
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- Commentary: Considering Treating Postoperative Atrial Fibrillation With Direct Oral AnticoagulantsSeminars in Thoracic and Cardiovascular SurgeryVol. 34Issue 3
- PreviewPostoperative atrial fibrillation (POAF) signifies often arrhythmia with ineffective blood circulation, which increases the risk of platelet adherence and thrombogenicity causing emboli. A pragmatic solution is to prescribe warfarin, though it requires constant laboratory monitoring. Direct oral anticoagulants (DOACs) enable a uniform dosing, though there is no evident means to control reversal of the anticoagulation effect.
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- Commentary: Moving the Dial on DOAC use Early After Cardiac SurgerySeminars in Thoracic and Cardiovascular SurgeryVol. 34Issue 3
- PreviewAtrial fibrillation remains an unsolved complication after cardiac surgery with published rates in the 20-50%.1,2 As outlined in a recent STS database analysis,3 over 60% of US surgeons still use warfarin rather than switching to direct oral anticoagulants (DOACs) for stroke prophylaxis in this clinical scenario. This trend persists despite the limitations associated with warfarin use, including prolonged and often turbulent early titration in new patients, dietary restrictions, strict monitoring requirements and extensive medication interactions.
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