1.
Exclusion criteria and adverse events in perioperative trials of tranexamic acid in cardiac surgery: a systematic review and meta-analysis
Khair S, Perelman I, Yates J, Taylor J, Lampron J, Tinmouth A, Saidenberg E
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2019
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.
2.
Risks of harms using antifibrinolytics in cardiac surgery: systematic review and network meta-analysis of randomised and observational studies
Hutton B, Joseph L, Fergusson D, Mazer CD, Shapiro S, Tinmouth A
Bmj.. 2012;345:e5798.
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Abstract
OBJECTIVE To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the suspension of aprotinin from the market in 2008 for safety reasons and its recent reintroduction in Europe and Canada. DESIGN Systematic review and network meta-analysis. DATA SOURCES A Cochrane review of antifibrinolytic treatments was chosen as the starting point for this systematic review. Medline, Embase, and the Cochrane register of trials were searched with no date restrictions for observational evidence. STUDY SELECTION Propensity matched or adjusted observational studies with two or more of the interventions of interest (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and no treatment) that were carried out in patients undergoing cardiac surgery. DATA ANALYSIS Network meta-analysis was used to compare treatments, and odds ratios with 95% credible intervals were estimated. Meta-analyses were carried out for randomised controlled trials alone and for randomised controlled trials with observational studies. RESULTS 106 randomised controlled trials and 11 observational studies (43 270 patients) were included. Based on the results from analysis of randomised controlled trials, tranexamic acid was associated on average with a reduced risk of death compared with aprotinin (odds ratio 0.64, 95% credible interval 0.41 to 0.99). When observational data were incorporated, comparisons showed an increased risk of mortality with aprotinin on average relative to tranexamic acid (odds ratio 0.71, 95% credible interval 0.50 to 0.98) and epsilon-aminocaproic acid (0.60, 0.43 to 0.87), and an increased risk of renal failure or dysfunction on average relative to all comparators: odds ratio 0.66 (95% credible interval 0.45 to 0.88) compared with no treatment, 0.66 (0.48 to 0.91) versus tranexamic acid, and 0.65 (0.45 to 0.88) versus epsilon-aminocaproic acid. CONCLUSION Although meta-analyses of randomised controlled trials were largely inconclusive, inclusion of observational data suggest concerns remain about the safety of aprotinin. Tranexamic and epsilon-aminocaproic acid are effective alternatives that may be safer for patients.