Effect of Ibuprofen versus acetaminophen on postpartum hypertension in preeclampsia with severe features: a double-masked, randomized controlled trial

BACKGROUND: Nonsteroidal antiinflammatory drug use has been shown to increase blood pressure in nonpregnant adults. Because of this, the American College of Obstetricians and Gynecologists suggests avoiding their use in women with postpartum hypertension; however, evidence to support this recommendation is lacking. OBJECTIVE: Our goal was to test the hypothesis that nonsteroidal antiinflammatory drugs, such as ibuprofen, adversely affect postpartum blood pressure control in women with preeclampsia with severe features. STUDY DESIGN: At delivery, we randomized women with preeclampsia with severe features to receive around-the-clock oral dosing with either 600 mg of ibuprofen or 650 mg of acetaminophen every 6 hours. Dosing began within 6 hours after delivery and continued until discharge, with opioid analgesics available as needed for breakthrough pain. Study drugs were encapsulated in identical capsules such that patients, nurses, and physicians were masked to study allocation. Exclusion criteria were serum aspartate aminotransferase or alanine aminotransferase >200 mg/dL, serum creatinine >1.0 mg/dL, infectious hepatitis, gastroesophageal reflux disease, age <18 years, or current incarceration. Our primary outcome was the duration of severe-range hypertension, defined as the time (in hours) from delivery to the last blood pressure >= 160/110 mm Hg. Secondary outcomes were time from delivery to last blood pressure >= 150/100 mm Hg, mean arterial pressure, need for antihypertensive medication at discharge, prolongation of hospital stay for blood pressure control, postpartum use of short-acting antihypertensives for acute blood pressure control, and opioid use for breakthrough pain. We analyzed all outcome data according to intention-to-treat principles. RESULTS: We assessed 154 women for eligibility, of whom 100 met entry criteria, agreed to participate, and were randomized to receive postpartum ibuprofen or acetaminophen for first-line pain control. Seven patients crossed over or did not receive their allocated study drug, and 93 completed the study protocol in their assigned groups. We found no differences in baseline characteristics between groups, including mode of delivery, body mass index, parity, race, chronic hypertension, and maximum blood pressure prior to delivery. We did not find a difference in the duration of severe-range hypertension in the ibuprofen vs acetaminophen groups (35.3 vs 38.0 hours, P = .30). There were no differences between groups in the secondary outcome measures of time from delivery to last blood pressure >= 150/100 mm Hg, postpartum mean arterial pressure, maximum postpartum systolic or diastolic blood pressures, any postpartum blood pressure >= 160/110 mm Hg, short-acting antihypertensive use for acute blood pressure control, length of postpartum stay, need to extend postpartum stay for blood pressure control, antihypertensive use at discharge, or opioid use for inadequate pain control. In a subgroup analysis of patients who experienced severe-range hypertension, the mean time to blood pressure control in the acetaminophen group was 68.4 hours and ibuprofen group was 56.7 hours (P = .26). At 6 weeks postpartum, there were no differences between groups in the rates of obstetric triage visits, hospital readmissions, continued opioid use, or continued antihypertensive use. CONCLUSION: The first-line use of ibuprofen rather than acetaminophen for postpartum pain did not lengthen the duration of severe-range hypertension in women with preeclampsia with severe features.