Conference Coverage

Ibuprofen appears safe with preeclampsia, study says


Key clinical point: Ibuprofen was as safe as acetaminophen in women with preeclampsia.

Major finding: The mean time to achieve postpartum blood pressure control was 35 hours in the ibuprofen group and 38 hours in the acetaminophen group.

Study details: The randomized study comprised 100 women.

Disclosures: The University of New Mexico sponsored the study. Dr. Blue reported having no financial disclosures.

Source: Blue N et al. The Pregnancy Meeting 2018 Abstract LB04.



– Compared to acetaminophen, ibuprofen does not prolong the time needed to control postpartum hypertension in women who experience preeclampsia with severe features, Nathan Blue MD, reported at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Ibuprofen did not exacerbate postpartum hypertension, as some studies have suggested, and women randomized to it for postpartum pain control reached their target blood pressure at a mean of 35 hours after delivery, similar to the 38 hours needed among women receiving acetaminophen.

Dr. Blue’s findings contradict the recommendation by the American College of Obstetricians and Gynecologists to avoid the use of ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) for pain control in women who experience preeclampsia or other hypertensive disorders of pregnancy.

“While our study was not meant to answer all questions about the potential problems of nonsteroidal anti-inflammatories [in this population], I would conclude from these results that providers and patients can make a decision together and feel good about the use of NSAIDs,” in the presence of postpartum hypertension, said Dr. Blue, a fellow at the University of New Mexico, Albuquerque.

Dr. Nathan Blue, a fellow at the University of New Mexico, Albuquerque Michele G. Sullivan/Frontline Medical News

Dr. Nathan Blue

The chronic use of these medications has been associated with hypertension in non-pregnant adults, Dr. Blue said. The mechanisms are not completely clear, but are hypothesized to include an inhibition of prostaglandin-dependent vasodilation; inhibition of aldosterone metabolism, leading to sodium retention; and an increase in arachidonic acid vasoactive metabolites via induction of the CYP450 pathway.

These concerns led ACOG to issue its recommendation in 2013 against the use of NSAIDs in pregnant women with hypertension.

“This is problematic, because NSAIDs are particularly well-suited to address obstetric pain,” Dr. Blue said at the meeting. “They have been shown to be better than acetaminophen for perineal injury and they are associated with a reduced use of opioids after cesarean section.”

To investigate the effect of ibuprofen on postpartum hypertension, Dr. Blue and his colleagues conducted a double-blind randomized controlled trial of 100 women with preeclampsia with severe features. The study population also included women who had chronic hypertension complicated by preeclampsia with severe features, and women with HELLP syndrome – a constellation of hemolysis, elevated liver enzymes, and low platelet count.

Women were randomized to either 600 mg ibuprofen or 650 mg acetaminophen every 6 hours, around the clock, with the first dose delivered within 6 hours of delivery. All patients received at least eight doses of their assigned medication. The primary endpoint was the time required to achieve blood pressure control. “We defined blood pressure control as the number of hours from delivery to the last reading of at least 160/110 mm Hg before discharge,” Dr. Blue said. “Our rationale here was that persistence of a blood pressure of that level would require a delay in discharge of at least 24 hours.”

The study had a number of secondary outcomes, including time from delivery to last blood pressure reading of at least 150/100 mm Hg; postpartum mean arterial pressure; any blood pressure reading of 160/110 mm Hg or higher; need for antihypertensive drugs at discharge; prolongation of hospital stay due to hypertension; and the need for postpartum opioids.

There was a 6-week follow-up assessment, at which time women reported any continued antihypertensive or opioid use, obstetrical triage visits after discharge, and hospital readmission.

The study cohort was well-balanced at baseline. Women were a mean of 30 years old; about a third were nulliparous, and half had a vaginal delivery. Chronic hypertension requiring medication was present in about 15%. The maximum blood pressure before delivery was about 180/107.

There was no significant difference between the ibuprofen group and the acetaminophen group in the primary endpoint of time to blood pressure of 160/110 mm Hg or below (35.3 vs. 38 hours). Nor were there significant differences in any of the secondary endpoints, including time to achieve a blood pressure of less than 150/100 mm Hg (58 vs. 57 hours), postpartum mean arterial pressure, maximum systolic and diastolic blood pressures, or the number of women who needed a short-acting antihypertensive (30 vs. 26) and who went home on an antihypertensive (33 vs. 31).

There were also no significant between-group differences in opioid use, either on postpartum days 0, 1, or 2. The total morphine equivalent dose for each group was likewise not significantly different (77 vs. 88 mg).

Dr. Blue was able to contact 77 women at 6 weeks’ postpartum. He found that 6-week outcomes were also similar. There were no significant differences in the number who required continuing antihypertensive or opioids, no difference in obstetric triage visits, and no difference in hospital readmission.

“Our study does not support the hypothesis that NSAIDs adversely affect blood pressure control in patients with preeclampsia,” he said. “Not only did we not find a difference in the primary outcome, we found not even a suggestion of difference in any measure of blood pressure control.”

The University of New Mexico sponsored the study. Dr. Blue reported having no financial disclosures.

SOURCE: Blue et al. The Pregnancy Meeting 2018 Abstract LB04.

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