Systematic Review and Meta-Analysis of Interventions to Slow Progression of Abdominal Aortic Aneurysm in Mouse Models

Abstract

Objective: There are no current effective abdominal aortic aneurysm (AAA) drug therapies. An important limitation of most preclinical studies is that they test the effect of drugs on AAA formation rather than AAA progression. The aim of this study was to systematically review AAA mouse model studies that have tested the effect of interventions in limiting the progression of preestablished AAA. Approach and Results: The literature search identified 35 studies meeting eligibility, and 30 (n=935 mice) contributed to the meta-analyses. AAAs were induced with angiotensin II (n=745 mice), calcium chloride (n=91 mice), or elastase (n=99 mice). Anti-inflammatory drugs (standardized mean difference [SMD], 1.62 [95% CI, 0.93–2.30]), protease inhibitors (SMD, 1.23 [95% CI, 0.52–1.95]), stem cells (SMD, 1.64 [95% CI, 1.05–2.24]), antiplatelet or anticoagulant drugs (SMD, 0.93 [95% CI, 0.63–1.22]), and renin-angiotensin system inhibitors (SMD, 1.45 [95% CI, 0.58–2.33]) reduced AAA diameter. Interventions initiated soon after model induction commenced were more likely to reduce AAA diameter (R 2 , 16%; P =0.007). Funnel plots suggested possible publication bias. Most studies did not report blinding or sample size calculations, and the risk of bias was considered medium or high in 20 (57%) of the 35 studies. Conclusions: There is low-quality evidence that a range of drugs are effective in limiting AAA progression when administered early after AAA induction in mouse models. Some of these drugs, such as antiplatelet and renin-angiotensin system inhibitors, have been reported to be ineffective in clinical trials.