Clinical efficacy and safety of anticoagulants in the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Background: Therapeutic management of idiopathic pulmonary fibrosis (IPF) remains challenging. IPF patients frequently exhibit a hypercoagulable state, and anticoagulant therapy has emerged as a potential strategy; however, its clinical utility remains controversial. Objectives: To systematically evaluate the efficacy and safety of anticoagulant therapy in IPF patients. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources and methods: Comprehensive searches were conducted in PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang Data, VIP, and CBM databases for randomised controlled trials (RCTs) investigating anticoagulant therapy in IPF, from database inception to February 2025. Two investigators independently screened the literature, extracted data, and assessed risk of bias. Meta-analysis was performed using RevMan 5.3. Results: Seven RCTs involving 504 patients with IPF were included. Compared with control groups not receiving anticoagulants, anticoagulant therapy significantly improved PaO 2 (MD = 11.64, 95% CI 7.09–16.18, p < 0.00001), SaO 2 (MD = 4.44, 95% CI 2.42–6.47, p < 0.0001), and HGF levels (MD = 108.74, 95% CI 88.58 to 128.90, p < 0.00001) but significantly reduced the mMRC score (MD = −0.38, 95% CI −0.62 to −0.14, p = 0.002) and D-dimer levels (MD = -0.08, 95% CI −0.11 to −0.05, p < 0.00001). No significant difference was observed in PaCO 2 levels (MD = −4.26, 95% CI −9.09 to 0.56, p = 0.08). Anticoagulant therapy did not demonstrate benefit in reducing all-cause mortality (RR = 3.46, 95% CI 1.57–7.61, p = 0.002) or adverse reactions (MD = 1.44, 95% CI 1.15–1.81, p = 0.002). Conclusion: Anticoagulant therapy may offer clinical benefits in IPF management. However, its lack of mortality benefit and safety concerns warrant cautious interpretation. Clinicians should carefully assess individual bleeding risks before initiating treatment. Due to the limited number of included studies and data constraints, further large-scale, high-quality, multicenter, and long-term RCTs are needed. Future research should prioritise risk stratification, optimised anticoagulation protocols and identification of biomarkers predictive of bleeding risk to inform clinical decision-making. Trial registration: The study protocol was registered with PROSPERO (Registration number: CRD42022349940).