We registered the analysis protocol under the registration number CRD42022326589, on the International Prospective Register of Systematic Reviews (PROSPERO). The analysis followed the guidelines provided in the Preferred Reporting of Systematic Reviews and Meta-Analysis (PRISMA) statement [7]. The primary objective of the analysis was to investigate the impact of antiplatelet treatment on sac volume in patients with AAA. To select relevant articles, the P.I.C.O. (patient: patients with AAA; intervention: antiplatelet treatment; comparison: antiplatelet medication vs. placebo or other medications; outcome: sac regression or expansion, and rupture, among others) model was utilized [8].

For this study, a search was conducted across four databases, EMBASE, Ovid, PubMed, and Scopus. The literature search strategy utilized the following keywords: (“aspirin” OR “clopidogrel” OR “antiplatelet”) AND (“abdominal aortic aneurysm” OR “aortic aneurysm repair” OR “aortic diameter” OR “growth rate”). The search was conducted up until March 2023. In addition, references for all included literature and for similar Meta-analyses were searched.

The inclusion criteria for this study were as follows: (1) reported results for cohorts of more than 10 patients receiving antiplatelet agents with at least one imaging data, and (2) compared the sac change of AAA patients receiving antiplatelet agents with that of patients receiving placebo or other agents without antiplatelet function. Studies that did not meet the following exclusion criteria were not considered: (1) case reports, meetings, and literature reviews, (2) studies that referred to biomarkers of AAA patients unless they included radiographic features of the sac volume, (3) articles with inadequate data (less than 25% of predefined variables extractable), and (4) studies reporting on the same population of patients. In the latter case, only the latest report was included unless the outcomes were mutually exclusive.

Duplicate citations were removed, and an independent reviewer was responsible for reviewing all titles and abstracts. Full-text versions of studies that met the inclusion criteria were obtained, and data extraction was performed by another independent reviewer. In cases where a consensus could not be reached between the two reviewers, a third reviewer was consulted to assist with the re-review of the full text of the article (Fig. 1). The extraction of data was performed by the first author and independently verified by the co-authors using a standardized data collection. Data collected included first author, publication year, study design, sample size, interventions, follow-up year, and outcome data (sac diameter reduction or expansion, and rupture).

Fig. 1.

Flow diagram adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines to illustrate the search and selection process during the initial stages of our review.

The Cochrane Risk of Bias tool was used to assess the quality of included randomized controlled studies, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases [9]. Non-randomized controlled studies were assessed by the Newcastle-Ottawa scale (NOS) for selection bias in the antiplatelet drug and control groups, comparability bias in the two cohorts, and outcome assessment bias [10].

The continuous variables were compared between the two groups using t-test and the categorical variables were compared using the $\chi$${}^2$-test. The random effects model was used to evaluate the results. The proportion was compared between the two groups to see if there was an overlap of 95% confidence intervals (CI) to assess statistical significance. Statistical analysis was performed using R software (Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org/. version 4.1).

We reviewed a total of 1872 references published within the predefined time frame of the analysis. Following a thorough examination of 22 articles, we ultimately included 13 studies that reported on the effects of antiplatelet agents on AAA progression in a total of 5392 patients (Table 1, Ref. [5, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22]). Three of them were randomized controlled clinical studies, two were prospective studies, and eight were retrospective studies. Eight studies reported on annual growth rate of sac diameter after taking antiplatelet agents; four reported on the number of cases of change in aneurysm diameter after taking antiplatelet agents; and one reported on aneurysm rupture after taking antiplatelet agents in patients. In terms of the following baseline characteristics: gender, smoking, and basic disease (including hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and chronic renal insufficiency), there were no significant differences between the antiplatelet drug group and the control group (p $>$ 0.05). However, there was a significantly higher proportion of patients with coronary artery disease in the antiplatelet drug group as compared to the control group ($\chi$${}^2$ = 8.286, p = 0.004 0.05) (Table 2).

Risk assessment using the Cochrane Risk Assessment Tool for all included randomized controlled clinical studies showed a low overall risk for these three studies [11, 12, 13] (Fig. 2). The quality of the literature for non-randomized controlled studies was assessed using the NOS scale and was high in all cases (Table 1).

Fig. 2.

Risk of bias. The ROBINS-I checklist for randomized trials was used to assess the methodological quality and potential risk of bias. ROBINS-1, Risk of Bias In Non-Randomized Studies of Interventions.

Of the total studies, the AAA growth rate was reported in eight studies (antiplatelet group: 1446, control group: 2540), including four with aspirin, one with ticagrelor, and three with any antiplatelet agents [11, 12, 13, 14, 15, 16, 17, 18]. Of all the literature, only one reported a reduction in AAA diameter with the use of antiplatelet agents (control group: 14.6 $\pm$ 11.8 mm/year vs. antiplatelet group: 9.4 $\pm$ 11.0 mm/year) [14]. We added a 16 mm/year diameter change based on all annual growth rates, and our meta-analysis did not reveal a statistically significant difference in the annual growth rate of AAA diameter with or without antiplatelet agents (mean difference (MD) = –0.04, 95% CI = [–0.37, 0.30]; heterogeneity: p 0.01, I${}^2$ = 91%, $\tau$${}^2$ = 0.1278) (Fig. 3).

Fig. 3.

Annual growth rate of AAA diameter (mm/year) in patients using antiplatelet agents vs. not using antiplatelet agents. SD, standard deviation; MD, mean difference; CI, confidence interval; AAA, abdominal aortic aneurysm.

Four studies (antiplatelet group: 731, control group: 447) reported on the number of cases of aneurysm diameter change after the use of antiplatelet agents, two with aspirin and two with any antiplatelet drug [19, 20, 21, 22]. Meta-analysis showed no significant difference between AAA diameter growth with or without antiplatelet agents (odds ratio (OR) = 0.96, 95% CI = [0.41, 2.25]; heterogeneity: p 0.01; I${}^2$ = 78%, $\tau$${}^2$ = 0.5849) (Fig. 4).

Fig. 4.

Number of patients (n) who experienced aneurysm diameter expansion using antiplatelet agents vs. not using antiplatelet agents. CI, confidence interval; OR, odds ratio.

Only one study described aneurysm rupture after the use of antiplatelet agents with a multifactorial Cox regression analysis showing that the risk of AAA rupture was not significantly altered with or without low-dose aspirin (hazard ratio (HR) = 1.019, 95% CI = [0.993, 1.044], p = 0.951) [5].