Clinical efficacy and adverse effects of LMWH combined with ASA in the treatment of RSA: A meta-analysis and systematic review

低分子肝素联合阿司匹林治疗复发性流产的临床疗效及不良反应:一项荟萃分析和系统评价

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Abstract

BACKGROUND: The incidence of recurrent spontaneous abortion (RSA) in the clinic shows an increasing trend year by year, and the coagulation status of this group of patients is mostly relatively abnormal. Currently, commonly used drugs in clinical practice include Aspirin (ASA) and low molecular weight heparin (LMWH), but their optimal treatment remains controversial. We aimed to evaluate the clinical efficacy and adverse effects of LMWH combined with ASA in the treatment of RSA. METHODS: Randomized controlled trials of LMWH combined with ASA for RSA were searched in the databases of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and Chinese Biomedical Literature Service System from the construction of the database to June 2024. Data were analyzed using Review Manager 5.3 and Stata software. Dichotomous variables were analyzed using relative risk (RR) and 95% confidence interval (CI) as their statistics. The included literature was assessed for bias and risk of bias of eligible studies using Cochrane risk of bias tool. The risk of bias was evaluated based on the evaluation criteria recommended by the Cochrane Guidance Manual for Systematic Evaluation. RESULTS: A total of 32 papers with a total of 3397 patients with RSA were finally included. LMWH combined with ASA treatment significantly improved the live birth rate (RR = 1.31, 95% CI: [1.19, 1.45], P < .00001), the rate of preterm stillbirths (RR = 0.23, 95% CI: [0.13, 0.40], P < .00001), rate of term delivery (RR = 1.55, 95% CI: [1.43, 1.67], P < .00001), rate of miscarriage (RR = 0.42, 95% CI: [0.36, 0.48], P < .00001), incidence of petechiae (RR = 0.44, 95% CI: [0.26, 0.72], P = .001), and incidence of thrombocytopenia (RR = 0.61, 95% CI: [0.39, 0.96], P = .03). In contrast, the incidence of preterm live births (RR = 1.07, 95% CI: [0.90, 1.28], P = .44), adverse reactions (RR = 0.77, 95% CI: [0.59, 1.00], P = .05), gingival bleeding (RR = 1.12, 95% CI: [0.65, 1.93], P = .69), and gastrointestinal reactions (RR = 0.87, 95% CI: [0.64, 1.17], P = .35) were not significant. CONCLUSION: LMWH combined with ASA treatment might improve pregnancy outcomes and reduces the incidence of adverse events in patients with RSA.

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