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Lasix for the prevention of de novo postpartum hypertension: a randomized placebo-controlled trial (LAPP Trial) - 03/09/24

Doi : 10.1016/j.ajog.2024.04.016 
Ukachi N. Emeruwa, MD, MPH a, b, , Hooman Azad, MD c, Samsiya Ona, MD a, d, Shai Bejerano, MS c, Sarah Alnafisee, MD c, Jordan Emont, MD, MPH, ScM c, Sharon Mathew, BA c, Michelle Batlle, MA e, Denice Arnold, MD e, Erinma P. Ukoha, MD, MPH a, Louise C. Laurent, MD, PhD b, Marni Jacobs, PhD f, Janice J. Aubey, MD, MPH c, Russell S. Miller, MD a, Cynthia Gyamfi-Bannerman, MD, MS b
a Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY 
b Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Diego School of Medicine, UC San Diego Health, San Diego, CA 
c Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital, New York, NY 
d Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine, Mount Sinai Health, New York, NY 
e XXX, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 
f Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Diego School of Medicine, UC San Diego Health, San Diego, CA 

Corresponding author: Ukachi N. Emeruwa, MD, MPH.
Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 03 September 2024

Abstract

Background

Birthing people with de novo postpartum hypertensive disorders continue to be among the populations at highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit of oral loop diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension.

Objective

This study aimed to evaluate whether oral furosemide can reduce the risk for de novo postpartum hypertension among high-risk birthing people by reducing postdelivery blood pressure.

Study Design

From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for de novo postpartum hypertension at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high risk for the development of de novo postpartum hypertension based on a prespecified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a 5-day course of 20-mg oral furosemide daily or identical-appearing placebo starting within 8 hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was mean arterial pressure averaged over the 24 hours before discharge or the 24 hours before antihypertensive therapy initiation. The study was powered to detect a 5 mm Hg difference in average mean arterial pressure (standard deviation, 6.4 mm Hg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of de novo postpartum hypertension, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes.

Results

The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between the groups. There was no significant difference in average mean arterial pressure in the 24 hours before discharge (or antihypertensive initiation) in the furosemide group (88.9±7.4 mm Hg) compared with the placebo group (86.8±7.1 mm Hg; absolute difference, 2.1 mm Hg; 95% confidence interval, −1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed de novo postpartum hypertension and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between the groups (P=.71 and P>.99, respectively).

Conclusion

De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces average mean arterial pressure in the 24 hours before discharge from the delivery hospitalization (or antihypertensive medication initiation) compared with placebo.

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Key words : antihypertensive therapy, health care innovation innovative technology, maternal health, maternal morbidity, neonatal outcomes, novel monitoring, oral furosemide, postpartum care, preventive therapies, remote monitoring technology, risk factor algorithm


Plan


 The authors report no conflict of interest.
 This study was funded by the Columbia University Irving Medical Center Maternal-Fetal Medicine Fellow Research Fund.
 ClincalTrials.gov
 Date of registration: February 12, 2021
 Date of initial participant enrollment: October 20, 2021
 Clinical trial identification number: NCT04752475
 URL of the registration site: NCT04752475
 Data sharing: Deidentified clinical data (including data dictionaries) that support the findings of this study are available for research purposes from the corresponding author upon reasonable request up to 3 years from the publication date. The study protocol and statistical analysis plan are available in the Supplement of this article.
 This study was presented at the 43rd Annual Pregnancy Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, February 6–11, 2023.
 Cite this article as: Emeruwa UN, Azad H, Ona S, et al. Lasix for the prevention of de novo postpartum hypertension: a randomized placebo-controlled trial (LAPP Trial). Am J Obstet Gynecol 2024;XX:x.ex–x.ex.


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