Cheap Drug Cuts Maternal Deaths Due to Postpartum Hemorrhage

Nicola M. Parry, DVM

April 26, 2017

Among women with postpartum hemorrhage, administration of tranexamic acid significantly reduces death due to bleeding, with no evidence of any adverse effects, results of a randomized controlled trial show.

The WOMAN (World Maternal Antifibrinolytic) Trial Collaborators published the results of their study online April 26 in The Lancet.

"When given soon after delivery, tranexamic acid reduces death due to bleeding by nearly one third," the collaborators write.

Lesley Regan, MD, DSc, from Imperial College London, United Kingdom, and president of the Royal College of Obstetricians and Gynaecologists, welcomed the results of the WOMAN trial.

These latest findings "show that early administration of a cheap, widely available, and heat-stable drug can reduce the number of maternal deaths from excessive bleeding after childbirth," Professor Regan said in a press statement.

Importantly, the results also provide "reassurance that there are no side effects from the drug for mothers or babies," she added.

Postpartum hemorrhage is the leading cause of maternal death, accounting for approximately 100,000 deaths globally each year. These deaths typically occur soon after delivery, and 99% occur in lower-income countries.

Fibrinolysis is known to be activated early after trauma and is associated with increased risk for death. The inexpensive antifibrinolytic drug tranexamic acid has been shown to reduce surgical blood loss and the need for reoperation to control bleeding, as well as deaths due to bleeding in trauma patients.

Fibrinolysis is also activated soon after childbirth, and the World Health Organization (WHO) recommends use of tranexamic acid in women with postpartum hemorrhage if uterotonics do not stop the bleeding, or if the bleeding is due to trauma.

Although this recommendation is based on results of clinical trials in tranexamic acid in surgery and trauma, data on its use in primary postpartum hemorrhage are lacking.

Therefore, researchers designed the international, randomized, double-blind, placebo-controlled WOMAN Trial to investigate the effect of early administration tranexamic acid for the treatment of postpartum hemorrhage.

The trial included women aged 16 years and older with a clinical diagnosis of postpartum hemorrhage after a vaginal birth or cesarean delivery. The primary analysis included data from 20,021 women who enrolled between March 2010 and April 2016 and who were randomly assigned to receive 1 g intravenous tranexamic acid or placebo by slow intravenous injection, in addition to usual care.

If bleeding continued after 30 minutes or stopped and restarted within 24 hours of receipt of treatment, participants could receive a second 1-g dose of tranexamic acid or placebo.

The primary outcome was a composite of death from all causes or hysterectomy within 42 days of randomization, and the main secondary outcome was death due to bleeding. All analyses were conducted on an intention-to-treat basis.

The results showed that treatment with tranexamic acid resulted in a significantly reduced risk for death due to bleeding compared with placebo (1.5% vs 1.9%; risk ratio [RR], 0.81; P = .045). The effect was greater among women who received treatment within 3 hours of delivery (1.2% vs 1.7%; RR, 0.69; P = .008).

Conversely, when women received treatment more than 3 hours after delivery, tranexamic acid did not significantly reduce the risk for death compared with placebo (2.6% vs 2.5%; RR, 1.07; P = .70).

However, the risk for death due to all other causes, including pulmonary embolism, organ failure, sepsis, and eclampsia, did not significantly differ between the two groups.

Similarly, treatment with tranexamic acid did not significantly reduce the risk for hysterectomy compared with placebo (3.6% vs 3.5%; RR, 1.02; P = .84), or the risk for death from all causes or hysterectomy (5.3% vs 5.5%; RR, 0.97; P = .65).

Adverse events did not differ significantly in the tranexamic acid vs placebo groups. Specifically, the risk for thromboembolic events was similar between the two groups (0.3% vs 0.3%; RR, 0.88; P = .603).

These findings support the inclusion of tranexamic acid in WHO treatment guidelines for primary postpartum hemorrhage but suggest that the drug should be administered as soon as possible after onset of bleeding.

The authors also recognize that in lower-income countries, many deaths from postpartum hemorrhage occur at home or in settings that preclude intravenous administration.

"Future research should assess the bioavailability of tranexamic acid after alternative (non-intravenous) routes of administration because this might facilitate its use in primary health-care settings," they conclude.

An accompanying editorial in The Lancet emphasizes that, despite progress in recent decades, "deaths during pregnancy and childbirth remain a serious (and largely preventable) risk for women in around 75 countries where 98% of maternal mortality occurs."

According to data from the United Nations (UN), the number of maternal deaths fell from 532,000 in 1990 to 303,000 by the end of the UN's Millennium Development Goal era in 2015. However, hemorrhage accounts for approximately 18% of these deaths.

The findings of the WOMAN Trial are therefore an important milestone in the quest to find new ways to prevent maternal death from bleeding, especially in lower-income countries, the editorial says.

This study was supported by grants from London School of Hygiene and Tropical Medicine, Pfizer, the UK Department of Health, the Wellcome Trust, and the Bill and Melinda Gates Foundation. The authors have disclosed no relevant financial relationships.

Lancet. Published online April 26, 2017.  Abstract, Editorial

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