The Effect of Medical Therapies for Subthreshold Abdominal Aortic Aneurysm Growth and Mortality: A Network Meta-Analysis of Randomized Controlled Trials

药物治疗对亚阈值腹主动脉瘤生长和死亡率的影响:随机对照试验的网络荟萃分析

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Abstract

OBJECTIVES: Abdominal aortic aneurysm (AAA) is often fatal when ruptured, and current guidelines suggest surgical management at suprathreshold sizes (50 mm for women or 55 mm for men) or with rapid expansion (>5 mm/year). Many medical therapies have been assessed for reducing subthreshold AAA expansion, though the evidence remains inconclusive. This network meta-analysis (NMA) compares AAA growth and mortality amongst medical treatments for AAAs. METHODS: MEDLINE (via PubMed), Scopus, Web of Science, EBSCO, and Cochrane Library databases were searched for relevant randomized controlled trials (RCTs) from database inception to 2024. Outcomes assessed included AAA growth rate, rate of referral for aneurysm surgery, overall mortality, and discontinuation from adverse effects. Data were analysed using R software, and P-score were used to rank different treatments. The GRADE framework was performed to assess the quality of evidence. RESULTS: Thirteen RCTs comprising 3084 patients were included in this NMA. Abdominal aortic aneurysm diameters ranged from 3.1 to 4.6 cm in the intervention group and 3.5-4.5 cm in the placebo group. Study-level mean annual growth rate ranged from 1.2 to 2.8 mm/year in the intervention group compared with placebo (1.2-2.6 mm/year). There were no significant differences in AAA growth among the compared groups (P-score probability in brackets): propranolol (0.73), telmisartan (0.66), antibiotics (0.53), placebo (0.53), ACE inhibitors (0.52), ticagrelor (0.46), and pemirolast (0.06). There were no significant differences among the compared groups in terms of aneurysm surgery referral rates, with propranolol (0.91), antibiotics (0.56), placebo (0.45), and pemirolast (0.08) showing similar outcomes. Similarly, no significant differences were observed in overall mortality rates across the groups, including telmisartan (0.87), antibiotics (0.57), ACE inhibitors (0.51), placebo (0.35), and propranolol (0.17). However, propranolol (OR = 3.14, 95% CI, 1.34-7.35) and ticagrelor (OR = 5.10, 95% CI, 1.12-23.18) were associated with a higher rate of discontinuation due to adverse events. Most of the studies analysed demonstrated moderate quality evidence. CONCLUSIONS: Current evidence highlights ongoing uncertainty regarding the efficacy of medical therapies in reducing subthreshold AAA growth rates, rates of referral for surgical repair, or overall mortality. The absence of statistically significant benefit may reflect underpowered datasets rather than definitive treatment inefficacy. Future large-scale, appropriately powered RCTs evaluating emerging medical treatments are required to accurately assess their clinical potential.

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