Efficacy of acetaminophen compared to ibuprofen for patent ductus arteriosus in preterm neonates: A systematic review and meta-analysis

doi:10.4330/wjc.v18.i5.118011

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May 26, 2026 (publication date) through May 20, 2026

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World Journal of Cardiology

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Cardiol. May 26, 2026; 18(5): 118011
Published online May 26, 2026. doi: 10.4330/wjc.v18.i5.118011

Efficacy of acetaminophen compared to ibuprofen for patent ductus arteriosus in preterm neonates: A systematic review and meta-analysis

Hakim Ullah Wazir, I M Khalid Reza, Maha Sajjad, Noora Inam, Tooba Fida, Noor Fatima, Aleena Sharif, Inayat Ullah, Sadaf Naz, Humaira, Muhammad Junaid Khan, Ali Dad, Hafiz Muhammad Moaaz Sajid, Usha Kumari, Salim Surani

Hakim Ullah Wazir, Noora Inam, Sadaf Naz, Humaira, Muhammad Junaid Khan, Ali Dad, Department of Medicine, Gujju Khan Medical College, Swabi 35100, Khyber Pakhtunkhwa, Pakistan

I M Khalid Reza, Department of Medicine, Enam Medical College and Hospital, Dhaka 1340, Bangladesh

Maha Sajjad, Department of Medicine, King Edward Medical University, Lahore 54000, Punjab, Pakistan

Tooba Fida, Department of Medicine, ISMMS/Valley Health, Paramus, NJ 07652, United States

Noor Fatima, Department of Medicine, Gomal Medical College, Dera Ismail Khan 29111, Pakistan

Aleena Sharif, Department of Medicine, Sheikh Zayed Hospital, Lahore 54600, Punjab, Pakistan

Inayat Ullah, Department of Pediatrics, Gujju Khan Medical College, Swabi 35100, Khyber Pakhtunkhwa, Pakistan

Hafiz Muhammad Moaaz Sajid, Department of Medicine, Faisalabad Medical University, Faisalabad 38000, Punjab, Pakistan

Usha Kumari, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States

Salim Surani, Department of Medicine, University of Houston, Houston, TX 77004, United States

Salim Surani, Department of Anesthesiology, Mayo Clinic, Rochester, MN 55902, United States

Salim Surani, Department of Medicine, Aga Khan University, Nairobi 00100, Kenya

Author contributions: Wazir HU was responsible for conceptualization, supervision, literature search, validation, screening, data interpretation, discussion, original draft writing, and revision, and editing; Reza IMK was responsible for screening, data extraction, and original draft writing; Sajjad M was responsible for statistical analysis and results writing; Inam N was responsible for screening, data extraction, and original draft writing; Fida T was responsible for original draft writing and data extraction; Fatima N was responsible for screening, risk biases, screening, and manuscript writing; Sharif A was responsible for original draft writing; Ullah I was responsible for validation, supervision, review and editing; Naz S was responsible for screening and data extraction; Humaira was responsible for data extraction and screening; Khan MJ was responsible for screening and writing original draft; Dad A was responsible for data extraction and writing original draft; Sajid HMM was responsible for Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart and supplementary figures; Kumari U was responsible for review and editing, and literature search; Surani S was responsible for overall supervision, revision, and editing; all of the authors read and approved the final version of the manuscript to be published.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.

Corresponding author: Salim Surani, MD, FACP, FCCP, Professor, Department of Medicine, University of Houston, 4302 University Drive, Houston, TX 77004, United States. srsurani@hotmail.com

Received: December 22, 2025
Revised: January 17, 2026
Accepted: March 23, 2026
Published online: May 26, 2026
Processing time: 149 Days and 16.9 Hours

Abstract

BACKGROUND

Patent ductus arteriosus (PDA) is prevalent in preterm neonates (< 37 weeks), often leading to respiratory distress and other complications. Ibuprofen, a nonsteroidal anti-inflammatory drug, achieves PDA closure in 70%-85% of cases but poses risks of renal impairment and gastrointestinal (GI) bleeding. Acetaminophen, with analgesic and antipyretic effects, is a potentially safer alternative. This study compares their efficacy and safety for PDA closure.

AIM

To assess the efficacy and safety of acetaminophen compared to ibuprofen for the treatment of PDA in preterm neonates.

METHODS

We conducted a systematic search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect for randomized controlled trials comparing ibuprofen and acetaminophen for PDA closure in preterm infants. Screening was done on Rayyan, and data on PDA closure and adverse effects were extracted into an Excel spreadsheet. Analysis was performed on Review Manager. A random-effects meta-analysis was performed, with risk ratios and 95%CI reported.

RESULTS

Total 18 randomized controlled trials were included, involving a total of 1946 preterm neonates with PDA. Acetaminophen was found to be just as effective as ibuprofen for closing a PDA in the first course of treatment [risk ratios (RR) = 0.99; 95%CI: 0.90-1.09; P = 0.86], in the second course of treatment (RR = 0.98, 95%CI: 0.89-1.09, P = 0.73), and overall (RR = 1.01, 95%CI: 0.97-1.06, P = 0.55). Rates of surgical ligation (RR = 0.72, 95%CI: 0.44-1.17, P = 0.86) and PDA reopening (RR = 1.23, 95%CI: 0.78-1.95, P = 0.38) did not differ. Both drugs were comparable in terms of safety outcomes, including necrotizing enterocolitis (RR = 1.10, 95%CI: 0.74-1.64, P = 0.64), intraventricular hemorrhage (RR = 0.96, 95%CI: 0.66-1.40, P = 0.84), hyperbilirubinemia (RR = 0.85, 95%CI: 0.50-1.43, P = 0.53), bronchopulmonary dysplasia (RR = 1.03, 95%CI: 0.58-1.82, P = 0.92), sepsis (RR = 0.88, 95%CI: 0.65-1.18, P = 0.40), pulmonary hemorrhage (RR = 0.71, 95%CI: 0.29-1.75, P = 0.46), retinopathy of prematurity (RR = 0.91, 95%CI: 0.65-1.18, P = 0.44). However, ibuprofen was associated with a higher risk of GI bleeding (RR = 0.32, 95%CI: 0.16-0.63, P = 0.001) and renal failure (RR = 0.37, 95%CI: 0.16-0.81, P = 0.01).

CONCLUSION

Acetaminophen is as effective as ibuprofen for PDA closure in preterm neonates, with a lower risk of GI bleeding and renal failure, making it a viable alternative.

Keywords: Patent ductus arteriosus; Acetaminophen; Ibuprofen; Preterm infants; Congenital heart disease

Core Tip: Eighteen randomized controlled trials involving 1946 patients were included. Acetaminophen demonstrates comparable efficacy to ibuprofen with a more favorable safety profile, particularly regarding gastrointestinal bleeding and renal complications. This study suggests acetaminophen as first-line pharmacologic therapy in preterm infants with contraindications to nonsteroidal anti-inflammatory drugs or increased bleeding risk/renal dysfunction.