Rapid Health Technology Assessment of Acetaminophen, Ibuprofen, Indometacin in the Treatment of Patent Ductus Arteriosus in Preterm Infants

OBJECTIVE To rapidly evaluate the effectiveness, safety and economy of acetaminophen(APAP), ibuprofen(IB), indometacin(ID) in the treatment of patent ductus arteriosus(PDA) in preterm infants, to provide evidence-based reference for clinical treatment.

METHODS Chinese and foreign databases such as PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, CBM, VIP and related health technology assessment websites were searched by computer. HTA reports, systematic evaluation/meta-analysis and pharmacoeconomic studies on APAP, IB, ID in the treatment of PDA were collected during the inception to October 31, 2024. Two researchers independently screened literature, extracted data, evaluated the quality of the literature, and conducted a descriptive analysis of the included research results.

RESULTS A total of 23 systematic evaluation/meta-analysis and 2 pharmacoeconomic studies were included. Effectiveness analysis showed that, there was no significant difference between APAP, IB and ID in the first and second course of treatment PDA closure rate, total PDA closure rate, PDA surgical closure rate and reopening rate. Further subdivided into the comparison of administration routes and doses, for PDA closure rate, Oral IB and APAP had advantages over the corresponding intravenous preparations. Among them, oral high-dose IB was more advantageous, followed by oral standard dose of APAP, oral standard dose of IB. Safety analysis showed that, compared with APAP, IB increased the incidence of renal dysfunction, oliguria, gastrointestinal bleeding/perforation and hyperbilirubinemia; ID increased the incidence of oliguria and neonatal necrotizing enterocolitis(NEC). Compared with IB, ID increased the incidence of oliguria, gastrointestinal bleeding/perforation, NEC. Economic analysis showed that, foreign studies indicated that APAP had a higher cost-effectiveness ratio in closed PDA successfully.

CONCLUSION Comprehen-sive analysis of effectiveness and safety, oral IB, oral APAP are recommended for symptomatic PDA. The overall safety of APAP is relatively good, followed by IB. However, the long-term effects of early exposure to APAP in premature infants remain unclear at present. APAP has better economic advantages in foreign countries, but domestic pharmacoeconomics studies are urgently needed.