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Exclusion criteria and adverse events in perioperative trials of tranexamic acid in cardiac surgery: a systematic review and meta-analysis

  • Simonne Khair
  • Iris Perelman
  • Jeffrey Yates
  • Joshua Taylor
  • Jacinthe Lampron
  • Alan Tinmouth
  • Elianna SaidenbergEmail author
Review Article/Brief Review

Abstract

Purpose

Tranexamic acid (TXA) reduces perioperative blood loss and transfusion requirement following cardiac surgery. Nevertheless, TXA remains underutilized because of concerns regarding development of adverse events. We conducted a systematic review to determine which patients are commonly excluded from TXA cardiac surgery clinical trials to determine if there are patient groups lacking safety data on TXA.

Methods

The databases Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until September 2017. Eligible studies were randomized-controlled trials (RCTs) administering systemic TXA perioperatively to patients undergoing any cardiac surgery. Our primary outcome was the exclusion criteria for each RCT, and the secondary endpoint was TXA safety. A descriptive synthesis was performed to analyze the exclusion criteria. TXA safety was assessed with meta-analysis.

Principal findings

Seventy eligible RCTs were included. The most common reasons for excluding patients from TXA cardiac surgery trials were major hepatic, renal, or cardiac comorbidities (76% of studies). Meta-analysis showed that TXA did not increase the risk of adverse events compared with placebo or no intervention (risk ratio, 0.97; 95% confidence interval, 0.88 to 1.07), including thrombosis and seizure.

Conclusion

We found that systemic TXA is safe to use in cardiac surgery. Certain patient groups are frequently excluded from TXA cardiac surgery trials, and may consequently have limited efficacy and safety data on TXA. Further research in these patient groups may be needed; nevertheless, for many patient populations there are sufficient data to inform evidence-based guidelines for TXA use in cardiac surgery.

Trial registration

PROSPERO (CRD42017060971); registered 4 April, 2017.

Critères d’exclusion et événements indésirables dans les études périopératoires sur l’utilisation d’acide tranexamique en chirurgie cardiaque : revue systématique et méta-analyse

Résumé

Objectif

L’acide tranexamique (ATX) réduit les pertes sanguines périopératoires et les besoins transfusionnels après une chirurgie cardiaque. L’ATX demeure toutefois sous-utilisé en raison de craintes quant à la survenue d’événements indésirables. Nous avons réalisé une revue systématique afin d’identifier les patients le plus fréquemment exclus des études cliniques sur l’utilisation d’ATX en chirurgie cardiaque pour déterminer si les données d’innocuité de l’ATX sont insuffisantes pour certains groupes de patients.

Méthode

Des recherches ont été effectuées dans les bases de données Medline, EMBASE et dans le Cochrane Central Register of Controlled Trials pour en tirer les études publiées jusqu’en septembre 2017. Pour être éligibles, les études devaient être des études randomisées contrôlées (ERC) examinant l’administration systémique d’ATX en période périopératoire à des patients subissant une chirurgie cardiaque, quelle qu’elle soit. Le critère d’évaluation principal de notre étude s’intéressait aux critères d’exclusion de chaque ERC, et le critère d’évaluation secondaire à l’innocuité de l’ATX. Une synthèse descriptive a été réalisée afin d’analyser les critères d’exclusion. L’innocuité de l’ATX a été évaluée par une méta-analyse.

Constatations principales

Soixante-dix ERC éligibles ont été incluses dans notre revue. Les raisons les plus fréquentes d’exclusion de patients des études d’ATX en chirurgie cardiaque étaient des comorbidités hépatiques, rénales ou cardiaques majeures (76 % des études). La méta-analyse a démontré que l’ATX n’augmentait pas le risque d’événements indésirables par rapport au placebo ou à toute autre intervention (risque relatif, 0,97; intervalle de confiance 95 %, 0,88 à 1,07), y compris le risque de thrombose ou de convulsion.

Conclusion

Nous avons observé que l’ATX par voie systémique peut être utilisé en toute sécurité en chirurgie cardiaque. Certains groupes de patients sont fréquemment exclus des études portant sur l’ATX en chirurgie cardiaque, et les données sur l’efficacité et l’innocuité de l’ATX dans ces populations pourraient par conséquent être limitées. Des recherches supplémentaires dans ces groupes pourraient être nécessaires; toutefois, les données pour plusieurs populations de patients sont suffisantes pour établir des directives fondées sur les données probantes concernant l’utilisation d’ATX en chirurgie cardiaque.

Enregistrement de l’étude

PROSPERO (CRD42017060971); enregistrée le 4 avril 2017.

Notes

Acknowledgements

We thank Dr. Benjamin Sohmer and Dr. Sean Dickie for their advice and expertise in the field of cardiac surgical anesthesia.

Conflicts of interest

Dr. Tinmouth is a consultant for Canadian Blood Services. The remaining authors have no conflicts of interest to disclose.

Editorial responsibility

This submission was handled by Dr. Philip M. Jones, Associate Editor, Canadian Journal of Anesthesia.

Author contributions

Elianna Saidenberg, Alan Tinmouth, Jacinthe Lampron, and Jeffrey Yates conceived the idea and design for this systematic review and meta-analysis. Jeffrey Yates, Iris Perelman, Simonne Khair, and Joshua Taylor performed all aspects of article selection and data abstraction. Jeffrey Yates and Iris Perelman conducted data analysis. Simonne Khair and Iris Perelman drafted the manuscript, with contributions and critical review from all other authors.

Funding

This work did not receive any funding.

Supplementary material

12630_2019_1393_MOESM1_ESM.pdf (137 kb)
Supplementary material 1 (PDF 137 kb)

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Copyright information

© Canadian Anesthesiologists' Society 2019

Authors and Affiliations

  1. 1.Faculty of MedicineUniversity of OttawaOttawaCanada
  2. 2.Clinical EpidemiologyOttawa Hospital Research InstituteOttawaCanada
  3. 3.Ottawa HospitalOttawaCanada

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