Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients
Objectives HALT-IT was an international, randomised trial which assessed the effects of tranexamic acid (TXA) in 12 009 patients with gastrointestinal (GI) bleeding. The results found no evidence that TXA reduces death. It is widely accepted that results of trials should be interpreted in the contex...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2023-02-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/13/2/e059982.full |
| _version_ | 1797895439127674880 |
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| author | Ian Roberts Haleema Shakur-Still Danielle Beaumont Katharine Ker Raoul Mansukhani Monica Arribas |
| author_facet | Ian Roberts Haleema Shakur-Still Danielle Beaumont Katharine Ker Raoul Mansukhani Monica Arribas |
| author_sort | Ian Roberts |
| collection | DOAJ |
| description | Objectives HALT-IT was an international, randomised trial which assessed the effects of tranexamic acid (TXA) in 12 009 patients with gastrointestinal (GI) bleeding. The results found no evidence that TXA reduces death. It is widely accepted that results of trials should be interpreted in the context of other relevant evidence. We conducted a systematic review and individual patient data (IPD) meta-analysis to assess if the results of HALT-IT are compatible with evidence for TXA in other bleeding conditions.Design Systematic review and IPD meta-analysis of randomised trials involving ≥5000 patients assessing TXA for bleeding. We searched our Antifibrinolytics Trials Register on 1 November 2022. Two authors extracted data and assessed risk of bias.Data synthesis We used a one-stage model to analyse IPD in a regression model stratified by trial. We assessed heterogeneity of the effect of TXA on death within 24 hours and vascular occlusive events (VOEs).Results We included IPD for 64 724 patients from four trials involving patients with traumatic, obstetric and GI bleeding. Risk of bias was low. There was no evidence for heterogeneity between trials for the effect of TXA on death or for the effect of TXA on VOEs. TXA reduced the odds of death by 16% (OR=0.84, 95% CI: 0.78 to 0.91, p<0.0001; p-heterogeneity=0.40). In patients treated within 3 hours of bleeding onset, TXA reduced the odds of death by 20% (0.80, 0.73 to 0.88, p<0.0001; p-heterogeneity=0.16). TXA did not increase the odds of VOEs (0.94, 0.81 to 1.08, p for effect=0.36; p-heterogeneity=0.27).Conclusions There is no evidence for statistical heterogeneity between trials assessing the effect of TXA on death or VOEs in different bleeding conditions. When the HALT-IT results are considered in the context of other evidence, a reduction in the risk of death cannot be discounted.Trial registration number PROSPERO CRD42019128260.Cite Now |
| first_indexed | 2024-04-10T07:26:51Z |
| format | Article |
| id | doaj.art-d9461c43fc2d41269f1fd404b578dc31 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-04-10T07:26:51Z |
| publishDate | 2023-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-d9461c43fc2d41269f1fd404b578dc312023-02-24T06:00:09ZengBMJ Publishing GroupBMJ Open2044-60552023-02-0113210.1136/bmjopen-2021-059982Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patientsIan Roberts0Haleema Shakur-Still1Danielle Beaumont2Katharine Ker3Raoul Mansukhani4Monica Arribas5Global Health Trials Group, Clinical Trials Unit, LSHTM, London, UKGlobal Health Trials Group, Clinical Trials Unit, LSHTM, London, UKGlobal Health Trials Group, Clinical Trials Unit, LSHTM, London, UKGlobal Health Trials Group, Clinical Trials Unit, LSHTM, London, UKGlobal Health Trials Group, Clinical Trials Unit, LSHTM, London, UKGlobal Health Trials Group, Clinical Trials Unit, LSHTM, London, UKObjectives HALT-IT was an international, randomised trial which assessed the effects of tranexamic acid (TXA) in 12 009 patients with gastrointestinal (GI) bleeding. The results found no evidence that TXA reduces death. It is widely accepted that results of trials should be interpreted in the context of other relevant evidence. We conducted a systematic review and individual patient data (IPD) meta-analysis to assess if the results of HALT-IT are compatible with evidence for TXA in other bleeding conditions.Design Systematic review and IPD meta-analysis of randomised trials involving ≥5000 patients assessing TXA for bleeding. We searched our Antifibrinolytics Trials Register on 1 November 2022. Two authors extracted data and assessed risk of bias.Data synthesis We used a one-stage model to analyse IPD in a regression model stratified by trial. We assessed heterogeneity of the effect of TXA on death within 24 hours and vascular occlusive events (VOEs).Results We included IPD for 64 724 patients from four trials involving patients with traumatic, obstetric and GI bleeding. Risk of bias was low. There was no evidence for heterogeneity between trials for the effect of TXA on death or for the effect of TXA on VOEs. TXA reduced the odds of death by 16% (OR=0.84, 95% CI: 0.78 to 0.91, p<0.0001; p-heterogeneity=0.40). In patients treated within 3 hours of bleeding onset, TXA reduced the odds of death by 20% (0.80, 0.73 to 0.88, p<0.0001; p-heterogeneity=0.16). TXA did not increase the odds of VOEs (0.94, 0.81 to 1.08, p for effect=0.36; p-heterogeneity=0.27).Conclusions There is no evidence for statistical heterogeneity between trials assessing the effect of TXA on death or VOEs in different bleeding conditions. When the HALT-IT results are considered in the context of other evidence, a reduction in the risk of death cannot be discounted.Trial registration number PROSPERO CRD42019128260.Cite Nowhttps://bmjopen.bmj.com/content/13/2/e059982.full |
| spellingShingle | Ian Roberts Haleema Shakur-Still Danielle Beaumont Katharine Ker Raoul Mansukhani Monica Arribas Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients BMJ Open |
| title | Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients |
| title_full | Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients |
| title_fullStr | Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients |
| title_full_unstemmed | Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients |
| title_short | Tranexamic acid for gastrointestinal bleeding: can a reduction in the risk of death be discounted? A systematic review and meta-analysis of individual patient data from 64 724 bleeding patients |
| title_sort | tranexamic acid for gastrointestinal bleeding can a reduction in the risk of death be discounted a systematic review and meta analysis of individual patient data from 64 724 bleeding patients |
| url | https://bmjopen.bmj.com/content/13/2/e059982.full |
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