Pharmacotherapy in Clinical Trials for Abdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis

Abstract

Objective There is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the efficacy of pharmacotherapy in limiting AAA growth and AAA-related events. Methods A systematic literature search was performed to examine the efficacy of pharmacotherapy in reducing AAA growth and AAA-related events. Pubmed, Embase (Excerpta Medica Database), and the Cochrane library were searched from March, 1999 to March 29, 2022. AAA growth (mm/year) in the intervention and control groups was expressed as mean and standard deviation (SD). The results of AAA growth were expressed as mean difference (MD) and its 95% confidence interval (95% CI). Odds ratios (ORs) were calculated for the AAA-related events.Heterogeneity was quantified using the I2 statistic. Forest plots were created to show the pooled results of each outcome. Outcomes A total of 1373 articles were found in different databases according to the search strategy, and 10 articles were identified by hand searching. A total of 26 articles were included in our systematic review after the screening. For the studies of metformin, the meta-analysis demonstrated that metformin use was associated with a lower AAA growth rate (MD: −0.81 mm/y, 95% CI: −1.19 to −0.42, P < 0.0001, I2 = 87%), Metformin use also was related to the lower rates of AAA-related events (OR: 0.53, 95% CI: 0.36 to 0.76, P = 0.0007, I2 = 60%). The hypotensive drugs of the studies mainly included angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), and propranolol. The overall meta-analysis of blood pressure-lowering drugs reported no significant effect in limiting the AAA growth (MD: 0.31mm/year, 95%CI: −0.03 to 0.65, P = 0.07, I2 = 66%) and AAA-related events (OR: 1.33, 95%CI: 0.76 to 2.32, P = 0.32, I2 = 98%), In the subgroup analysis of the hypotensive drugs, the ACEI/ARB and propranolol also showed no significant in reducing the AAA growth and AAA-related events. The meta-analysis of the antibiotics demonstrated that the antibiotics were not associated with a lower AAA growth rate (MD: −0.27 mm/y, 95% CI: −0.88 to 0.34, P = 0.39, I2 = 77%) and AAA-related events (OR: 0.94, 95%CI: 0.65 to 1.35, P = 0.72, I2 = 0%). The results of statins also showed no significant effect in limiting AAA growth (MD: −1.11mm/year, 95%CI: −2.38 to 0.16, P = 0.09, I2 = 96%) and AAA-related events (OR: 0.53, 95%CI: 0.26 to 1.06, P = 0.07, I2 = 92%). Conclusion In conclusion, effective pharmacotherapy for AAA was still lacking. Although the meta-analysis showed that metformin use was associated with lower AAA growth and AAA-related events, all of the included studies about metformin were cohort studies or case-control studies. More randomized controlled trials (RCTs) are needed for further verification.

The role of diabetes on the development of abdominal aortic aneurysms (AAA)

“…This prompted the question of whether anti-diabetic medications are the source of the protective impact of diabetes mellitus. [18,31,32] GLP-1RAs, like liraglutide and lixisenatide, prevent AAA development in animal models by preserving the extracellular matrix and exerting anti-inflammatory and antioxidant properties. Lixisenatide inhibits the production of reactive oxygen species (ROS) and oxidative DNA damage, which in turn delays the release of pro-inflammatory cytokines, macrophage filtration, and ultimately MMPs.…”

Novel pharmacological approaches in abdominal aortic aneurysm

“…Half of them argued in favour of a lower aneurysm growth rate in patients on statin therapy, while others, specifically the largest and most robust trials, reported no significant benefit on AAA progression [15]. Similarly, systematic reviews and meta-analyses of observational studies assessing the effect of statin therapy on growth outcomes led to discordant conclusions [16][17][18]. Consequently, the use of statins as a pharmacological approach to halt AAA growth remains uncertain.…”

“…Inconsistent data regarding AAA progression [16][17][18]. Statins improve survival after AAA repair [16,19,20].…”

Double-edged sword of diabetes mellitus for abdominal aortic aneurysm

“…Previous studies illustrated the negative association between metformin and development of AAA. Metformin was shown to retard the formation and growth rate of AAA (56), even in normoglycemic mice (52, 57). Golledge et al revealed that patients with diabetes prescribed metformin were associated with significantly lower AAA repair and rupture-related mortality comparing to patients with diabetes not prescribed metformin or patients with no diabetes.…”