Winning hearts and minds Tranexamic acid and life threatening bleeding

TXA reduces bleeding in surgery (Ker et al, 2012) TXA TXA betterTXA worse 0.62 ( ) RR (95% CI) Transfusion TXA RR (95% CI) TXA betterTXA worse ( ) Mortality TXA and bleeding 95 trials72 trials

10,096 allocated TXA10,115 allocated placebo 10,093 baseline data10,114 baseline data Followed up = 10,060 (99.7%) Followed up = 10,067 (99.5%) 20,211 randomised 1 consent withdrawn 47 lost to follow-up 33 lost to follow-up 3 consent withdrawn CRASH-2 trial profile

Any cause of death TXA worseTXA better RR (95% CI) TXA (n= 10,060) 1,463 (14.5%) Placebo (n= 10,067) 1,613 (16.0%) 0.91 (0.85–0.97) 2P=0.0035

Death due to bleeding TXA worseTXA better RR (95% CI) TXA (n= 10,060) 489 (4.9%) Placebo (n= 10,067) 574 (5.7%) 0.85 (0.76–0.96) 2P=0.0077

Effect of early TXA on death due to bleeding (by geographical region) EU, Australia, Canada48 Asia 114 Latin America 56 Africa 52 World RR (95% CI) P=0.70 TXA worse TXA better Hospitals 0.72 (0.63–0.83)

Fig 1 Deaths from all causes in patients with traumatic bleeding according to treatment with tranexamic acid (P=0.96 for heterogeneity). Roberts I et al. BMJ 2012;345:bmj.e5839 ©2012 by British Medical Journal Publishing Group

Fig 2 Death from bleeding in patients with traumatic bleeding according to treatment with tranexamic acid (P=0.98 for heterogeneity). Roberts I et al. BMJ 2012;345:bmj.e5839 ©2012 by British Medical Journal Publishing Group

Fig 4 Distribution of patients with traumatic bleeding in UK Trauma Audit and Research Network by baseline risk of death. Roberts I et al. BMJ 2012;345:bmj.e5839 ©2012 by British Medical Journal Publishing Group

Fig 5 Distribution of estimated premature deaths in patients with traumatic bleeding potentially averted with administration of tranexamic acid. Roberts I et al. BMJ 2012;345:bmj.e5839 ©2012 by British Medical Journal Publishing Group

2,161 reports 1,454(68%)commentaries 555 (25%)case reports 41 ( 2%)non-experimental 60 ( 3%)randomized trials 51 ( 2%) systematic reviews Financial affiliation with manufacturer: 3 times more likely to recommend use 4 times more likely to downplay side effects Novo-seven literature 2010