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Meta-Analysis
. 2019 Oct 10:367:l5476.
doi: 10.1136/bmj.l5476.

Antithrombotic treatment after coronary artery bypass graft surgery: systematic review and network meta-analysis

Karla Solo  1   2 , Shahar Lavi  3 , Conrad Kabali  4 , Glenn N Levine  5 , Alexander Kulik  6 , Ava A John-Baptiste  1   7   8 , Stephen E Fremes  9   10 , Janet Martin  1   7 , John W Eikelboom  11 , Marc Ruel  12 , Ashlay A Huitema  3 , Tawfiq Choudhury  3 , Deepak L Bhatt  13 , Nikolaos Tzemos  3 , Mamas A Mamas  14 , Rodrigo Bagur  15   3   14
Affiliations
Meta-Analysis

Antithrombotic treatment after coronary artery bypass graft surgery: systematic review and network meta-analysis

Karla Solo et al. BMJ. .

Abstract

Objective: To assess the effects of different oral antithrombotic drugs that prevent saphenous vein graft failure in patients undergoing coronary artery bypass graft surgery.

Design: Systematic review and network meta-analysis.

Data sources: Medline, Embase, Web of Science, CINAHL, and the Cochrane Library from inception to 25 January 2019. ELIGIBILITY CRITERIA: for selecting studies Randomised controlled trials of participants (aged ≥18) who received oral antithrombotic drugs (antiplatelets or anticoagulants) to prevent saphenous vein graft failure after coronary artery bypass graft surgery.

Main outcome measures: The primary efficacy endpoint was saphenous vein graft failure and the primary safety endpoint was major bleeding. Secondary endpoints were myocardial infarction and death.

Results: This review identified 3266 citations, and 21 articles that related to 20 randomised controlled trials were included in the network meta-analysis. These 20 trials comprised 4803 participants and investigated nine different interventions (eight active and one placebo). Moderate certainty evidence supports the use of dual antiplatelet therapy with either aspirin plus ticagrelor (odds ratio 0.50, 95% confidence interval 0.31 to 0.79, number needed to treat 10) or aspirin plus clopidogrel (0.60, 0.42 to 0.86, 19) to reduce saphenous vein graft failure when compared with aspirin monotherapy. The study found no strong evidence of differences in major bleeding, myocardial infarction, and death among different antithrombotic therapies. The possibility of intransitivity could not be ruled out; however, between-trial heterogeneity and incoherence were low in all included analyses. Sensitivity analysis using per graft data did not change the effect estimates.

Conclusions: The results of this network meta-analysis suggest an important absolute benefit of adding ticagrelor or clopidogrel to aspirin to prevent saphenous vein graft failure after coronary artery bypass graft surgery. Dual antiplatelet therapy after surgery should be tailored to the patient by balancing the safety and efficacy profile of the drug intervention against important patient outcomes.

Study registration: PROSPERO registration number CRD42017065678.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work. AK receives research support for the Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET) study (ClinicalTrials.gov: NCT02053909) from AstraZeneca, outside the submitted work; JWE has received honoraria and research support from Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Glaxo Smith Kline, Janssen, Sanofi Aventis and Eli Lilly, as well as a personnel award from the Heart and Stroke Foundation of Canada, outside the submitted work; DLB reports grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company, Roche, Pfizer, Forest Laboratories/AstraZeneca, Ischemix, Amgen, Lilly, Chiesi, Ironwood, Abbott, Regeneron, Idorsia, Synaptic, Afimmune; other from FlowCo, PLx Pharma, Takeda, Medscape Cardiology, Regado Biosciences, Boston VA Research Institute, Clinical Cardiology, VA, St Jude Medical (now Abbott), Biotronik, Cardax, Boston Scientific, Svelte, Merck, Novo Nordisk, CSL Behring, Fractyl; personal fees from Duke Clinical Research Institute, Mayo Clinic, Population Health Research Institute, Belvoir Publications, Slack Publications, WebMD, Elsevier, HMP Global, Harvard Clinical Research Institute (now Baim Institute for Clinical Research), Journal of the American College of Cardiology, Cleveland Clinic, Mount Sinai School of Medicine, TobeSoft, Bayer, Medtelligence/ReachMD, Cereno Scientific, Ferring Pharmaceuticals; personal fees, non-financial support, and other from American College of Cardiology; personal fees and non-financial support from Society of Cardiovascular Patient Care; non-financial support from American Heart Association; grants and other from PhaseBio; personal fees and other from Boehringer Ingelheim, outside the submitted work. The remaining authors have nothing to disclose.

Figures

Fig 1
Fig 1
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram
Fig 2
Fig 2
Network of treatment comparisons for saphenous vein graft failure (primary efficacy outcome) and major bleeding (primary safety outcome). Each node represents different active interventions or placebo. Size of nodes is proportional to number of studies comparing respective nodes. Increasing thickness of lines between nodes is proportional to number of randomly assigned patients contributing to direct comparisons. Vit K A=vitamin K antagonist
Fig 3
Fig 3
Network meta-analysis and certainty of evidence for saphenous vein graft failure (primary efficacy outcome) and major bleeding (primary safety outcome). Results are odds ratios (95% confidence intervals) from the network meta-analysis between the column defining intervention and row defining intervention. Significant results are in bold. Certainty of evidence is also given: green=moderate certainty evidence, yellow=low certainty evidence, red=very low certainty evidence
Fig 4
Fig 4
Network of treatment comparisons for secondary outcomes all cause mortality and myocardial infarction. Each node represents different active interventions or placebo. Size of nodes is proportional to number of studies comparing respective nodes. Increasing thickness of lines between nodes is proportional to number of randomly assigned patients contributing to direct comparisons. Vit K A=vitamin K antagonist
Fig 5
Fig 5
Network meta-analysis and certainty of evidence for secondary outcomes all cause mortality and myocardial infarction. Results are odds ratios (95% confidence intervals) from the network meta-analysis between the column defining intervention and the row defining intervention. Certainty of evidence is also given: green=moderate certainty evidence, yellow=low certainty evidence, red=very low certainty evidence
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