Other Supporting Document for Abdominal Aortic Aneurysm: Screening
By Janelle M. Guirguis-Blake, MD; Tracy L. Beil, MS; Caitlyn A. Senger, MPH; and Erin L. Coppola, MPH
The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.
This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was published in JAMA on December 10, 2019 (JAMA. 2019;322(22):2219-2238. doi:10.1001/jama.2019.17021).
Importance: Ruptured abdominal aortic aneurysms (AAAs) have mortality estimated at 81%.
Objective: To systematically review the evidence on benefits and harms of AAA screening and small aneurysm treatment to inform the US Preventive Services Task Force.
Data Sources: MEDLINE, PubMed (publisher supplied only), Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials for relevant English-language studies published through September 2018. Surveillance continued through July 2019.
Study Selection: Trials of AAA screening benefits and harms; trials and cohort studies of small (3.0-5.4 cm) AAA treatment benefits and harms.
Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and extracted data. The Peto method was used to pool odds ratios (ORs) for AAA-related mortality, rupture, and operations; the DerSimonian and Laird random-effects model was used to pool calculated risk ratios for all-cause mortality.
Main Outcomes and Measures: AAA and all-cause mortality; AAA rupture; treatment complications.
Results: Fifty studies (N = 323,279) met inclusion criteria. Meta-analysis of population-based randomized clinical trials (RCTs) estimated that a screening invitation to men 65 years or older was associated with a reduction in AAA-related mortality over 12 to 15 years (OR, 0.65 [95% CI, 0.57-0.74]; 4 RCTs [n = 124,926]), AAA-related ruptures over 12 to 15 years (OR, 0.62 [95% CI, 0.55-0.70]; 4 RCTs [n = 124,929]), and emergency surgical procedures over 4 to 15 years (OR, 0.57 [95% CI, 0.48-0.68]; 5 RCTS [n = 175,085]). In contrast, no significant association with all-cause mortality benefit was seen at 12- to 15-year follow-up (relative risk, 0.99 [95% CI 0.98-1.00]; 4 RCTs [n = 124,929]). One-time screening was associated with significantly more procedures over 4 to 15 years in the invited group compared with the control group (OR, 1.44 [95% CI, 1.34-1.55]; 5 RCTs [n = 175,085]). Four trials (n = 3314) of small aneurysm surgical treatment demonstrated no significant difference in AAA-related mortality or all-cause mortality compared with surveillance over 1.7 to 12 years. These 4 early surgery trials showed a substantial increase in procedures in the early surgery group. For small aneurysm treatment, registry data (3 studies [n = 14,424]) showed that women had higher surgical complications and postoperative mortality compared with men.
Conclusions and Relevance: One-time AAA screening in men 65 years or older was associated with decreased AAA-related mortality and rupture rates but was not associated with all-cause mortality benefit. Higher rates of elective surgery but no long-term differences in quality of life resulted from screening.
Abdominal aortic aneurysms (AAAs) are often asymptomatic, with slow expansion until rupture. AAA screening to identify and treat aneurysms before rupture can potentially prevent a fatal outcome. To prevent rupture, AAA, defined as an aneurysm 3.0 cm in diameter or larger, is most commonly surgically repaired via open repair or endovascular aneurysm repair (EVAR) when it reaches a diameter of 5.5 cm.1-3 The role of pharmacotherapy to slow aneurysm expansion has been uncertain.4
Reported AAA prevalence rates in persons 60 years or older have declined from 3.9% to 7.2% in the 1990s5, 6 to more contemporary estimates that range from 1.2% to 3.3%.7, 8 The most important risk factors for the development of AAA include advanced age,9, 10 male sex,10, 11 smoking,4, 11-13 and family history of AAA.12-14
In 2014, the US Preventive Services Task Force (USPSTF) recommended 1-time screening for AAA by ultrasonography in asymptomatic men aged 65 to 75 years who have ever smoked (B recommendation).15 The USPSTF concluded that the benefits of screening do not clearly outweigh the possible harms and recommended that clinicians selectively offer screening for AAA in men aged 65 to 75 years who have never smoked (C recommendation).15 Also, the USPSTF recommended against routine screening for AAA in asymptomatic women who have never smoked (D recommendation) and determined that there was insufficient evidence for screening women aged 65 to 75 years who have ever smoked (I statement).15 This review was prepared to inform an updated recommendation by the USPSTF on the evidence related to the effectiveness of 1-time and repeat screening for AAA and possible related harms, as well as the effectiveness and related harms of treatment (pharmacotherapy or surgery) of small AAAs (3.0-5.4 cm in diameter).
Scope of Review
Five key questions (KQs) (Figure 1) were developed to identify the benefits (KQ1) and harms (KQ3) of 1-time screening for AAA, the effects of rescreening for AAA on health outcomes or AAA incidence (KQ2), and the effectiveness (KQ4) and harms (KQ5) of treatment of small AAA (3.0-5.4 cm in diameter). Additional methodological details are publicly available in the full evidence report at https://www.uspreventiveservicestaskforce.org/Page/Document/ UpdateSummaryFinal/abdominal-aortic-aneurysm-screening1.
Data Sources and Searches
To identify studies published since the 2014 USPSTF review,17 literature searches were conducted from January 2013 through September 4, 2018, in MEDLINE, PubMed (for publisher-supplied records only), the Database of Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled Trials. Additional studies were located by reviewing reference lists of other systematic reviews and through suggestions by experts. Ongoing surveillance was conducted after September 2018 through July 26, 2019, to identify newly published studies that may affect the findings of the review. This was accomplished through targeted searches of journals with a high impact factor and journals relevant to the topic to identify major studies that might affect the conclusions or understanding of the evidence and therefore the related USPSTF recommendation. No additional articles were identified during the surveillance period.
Two reviewers independently evaluated articles from the previous review in addition to citations and full-text articles from the literature searches against specified inclusion criteria. Eligible screening studies used ultrasound as the screening modality for identifying AAA in asymptomatic adults older than 50 years. Only randomized clinical trials (RCTs) comparing 1-time screening with no screening were used to evaluate the effectiveness of screening for AAA (KQ1). When assessing the benefits of repeated AAA screening and the harms of screening for AAA, RCTs and large cohort studies (n ≥1000) of asymptomatic adult populations were considered (KQ2 and KQ3). Studies of the effectiveness of treatment and related harms focused on individuals with small AAAs (3.0-5.4 cm in diameter) because the majority of screen-detected aneurysms are small. The effectiveness of treating small AAAs (KQ4) was examined through RCTs evaluating surgical intervention or pharmacotherapeutic treatment compared with surveillance, usual care, or placebo. The criteria for assessing harms of treating small AAAs (KQ5) included RCTs, observational studies, and registry data related to surgical harms. The results for pharmacotherapy interventions for KQ4 and KQ5 are not reported in depth in this article but are available in the full report.
Data Extraction and Quality Assessment
Two reviewers applied USPSTF design-specific criteria16 to assess the methodological quality of all eligible studies, and studies were evaluated to be good or fair quality using items from the Newcastle-Ottawa Scale18 and USPSTF quality rating standards.16 Each study was assigned a quality rating of “good,” “fair,” or “poor.” Discordant quality ratings were resolved by discussion or by a third reviewer and adjudicated as needed. Studies were rated as poor quality and excluded if there was a major flaw such as very high attrition (generally >40%); differential attrition between intervention groups (generally >20%); substantial lack of baseline comparability between groups without adjustment; or major concerns about the trial conduct, analysis, or reporting of results. Poor-quality observational studies had multiple threats to internal validity and were excluded from the review. One reviewer extracted data from all included studies rated as fair or good quality directly into summary tables, and a second reviewer checked the data for accuracy.
Subpopulations of interest were selected a priori based on the previous review and recommendation statement, established characteristics associated with the development of AAA, and feedback received from 3 key informants during the scoping phase. The subpopulation approach described in Whitlock et al19 was followed to audit outcomes and rate the credibility of the subpopulation data provided by included studies.
Data Synthesis and Analysis
To evaluate the effectiveness of screening for AAA, all-cause mortality and AAA-related mortality, rupture, and emergency surgical procedures were examined in RCTs that compared screening vs no screening. The primary analysis for all-cause mortality pooled calculated risk ratios using the DerSimonian and Laird20 random-effects model, since statistical heterogeneity was low (I2 = 0%, τ2 = 0.0). The Peto method was used to pool odds ratios (ORs) for AAA-related mortality, rupture, and emergency surgical procedures because events were rare and trials had a similar number of participants in both study groups.21
Meta-analyses of the rescreening studies included in KQ2 were not conducted because of substantial differences in patient population, length of follow-up, and outcomes reported.
To analyze the harms of screening vs no screening in KQ3, 30-day mortality after elective surgery, 30-day mortality after emergency surgery, overall operations, elective operations, emergency operations, and quality of life (QOL) measures were examined. Only 2 trials reported 30-day mortality after elective surgery and 30-day mortality after emergency surgery outcomes; therefore, those trials were not pooled. The Peto method was used to pool overall operations, elective operations, and emergency operations, as described under KQ1. Because of the substantial difference in quality-of-life measurements and insufficient reporting of data (eg, lack of variation parameters), these data could not be pooled in the studies of screening vs no screening.
All statistical testing was 2-sided, and P < 0.05 was considered statistically significant. Statistical heterogeneity was examined across trials with the I2 statistic and χ2 test of heterogeneity. Stata version 15.1 (StataCorp) was used for all analyses.
The effectiveness of early intervention (KQ4) and associated harms of treating small AAAs (KQ5) was evaluated by capturing AAA growth, all-cause mortality, AAA-related mortality, and aneurysm ruptures. The data were narratively described and presented in data tables. Meta-analyses were not conducted because of the small number of studies of each intervention type.
The strength of evidence was rated for each key question based on consistency (similarity of effect direction and size), precision (degree of certainty around an estimate), reporting bias (potential for bias related to publication, selective outcome reporting, or selective analysis reporting), and study quality (ie, study limitations.
Two reviewers evaluated 3946 citations and 137 full-text articles against inclusion criteria, and 33 studies (69 articles)5, 6, 8, 22-88 met inclusion criteria for this systematic review (Figure 2). Nine new studies were included (4 RCTs,24, 57, 63, 79 2 cohort studies,80, 82 and 3 registry studies27, 60, 70) and 24 studies (13 RCTs, 8 cohort studies, 1 case-control study, and 2 registry studies) were carried forward from the previous USPSTF report.
Benefits of Screening
Key Question 1. What are the effects of 1-time screening for AAA on health outcomes in an asymptomatic population 50 years or older?
Two fair-5, 23 and 2 good-quality6, 83 population-based screening RCTs assessed AAA screening effectiveness on AAA-specific mortality and all-cause mortality (Table 1): the Multicenter Aneurysm Screening Study (MASS);22, 45, 46, 83, 84 the Chichester, United Kingdom, screening trial;23, 76, 78, 86 the Viborg County, Denmark, screening trial;6, 54-56, 58 and the Western Australia screening trial.5, 65, 66, 81, 88 The trials randomized participants to either an invitation to 1-time ultrasound screening or a usual care control group. All trials defined AAA as an aortic diameter of 3.0 cm or greater, and AAA prevalence varied from 4% to 7.6%; the majority of screen-detected AAAs were smaller than 4.5 cm in diameter. Mean or median follow-up in these 4 population-based screening trials ranged from 12.8 to 15 years, with short-term results published at 3- to 5-year intervals.
One additional new population-based screening trial in Denmark (Viborg Vascular [VIVA]) was included solely for the outcome of number of operations.57 VIVA randomized participants to a multicomponent screening vs no screening for hypertension, peripheral artery disease, and AAA. Participants with confirmed AAA or peripheral artery disease were counseled to initiate preventive interventions, with aspirin and statin therapy prescribed to those meeting a total cholesterol threshold value.57 The effects of AAA screening alone could not be independently assessed with respect to all-cause mortality or AAA mortality because multicomponent screening and cardiovascular disease (CVD)–prevention interventions were administered; however, the number of procedures was included in this review, as they would almost exclusively be expected to be attributable to AAA screening.
AAA-specific mortality in men was the primary outcome of the 4 screening trials. A meta-analysis of the trials5, 23, 58, 83 (n = 124,929) estimated a statistically significant lower AAA-specific mortality over 12 to 15 years of follow-up associated with an invitation to screening, with high heterogeneity (Peto OR, 0.65 [95% CI, 0.57-0.74]; I2 = 80%; number needed to screen, 305 men [95% CI, 248-411]) (Figure 3). A meta-analysis of all-cause mortality in men from the 4 screening trials5, 23, 58, 83 (n = 124,929) did not reach statistical significance (relative risk [RR], 0.99 [95% CI, 0.98-1.00]; I2 = 0%) (Figure 4). Only the MASS trial reported a statistically significant lower all-cause mortality (hazard ratio, 0.97 [95% CI, 0.95-0.99]).83 In addition to mortality outcomes, the screening trials reported ruptures and emergency operations among primarily male study populations. Pooled results of 4 trials5, 23, 58, 83 (n = 124,929) showed a statistically significant lower risk of AAA rupture associated with the invitation to screening (Peto OR, 0.62 [95% CI, 0.55- 0.70]; I2 = 53%; number needed to screen, 246 men [95% CI, 207- 311]) (Figure 3). An invitation to screening in 5 trials5, 23, 57, 58, 83 (n = 175,085) was also associated with a statistically significant lower risk of emergency operations in the screening group (Peto OR, 0.57 [95% CI, 0.48-0.68]; I2 = 27%) (Figure 5). This would reduce the number of emergency procedures by 2 per 1000 men screened (95% CI, 2-2).
Patients invited to participate in the screening trials were predominantly men. Only the Chichester trial23, 76 examined AAA screening in women (59% of participants [n = 9342] were women), showing that women had a lower AAA prevalence compared with men (1.3% vs 7.6%).76, 78 There was no significant difference between the invited and control groups for women in AAA-related or all-cause mortality at 5 years (AAA mortality: 0.06% vs 0.04%; all-cause mortality: 10.7% vs 10.2%) or AAA rupture rate at 10-year follow-up (0.2% in both groups), but the trial was underpowered.
Benefits of Rescreening
Key Question 2. What are the effects of rescreening for AAA on health outcomes or AAA incidence in a previously screened, asymptomatic population without AAA on initial screening?
No trial-level evidence examined the effectiveness of 1-time screening plus rescreening compared with 1-time screening alone. Seven cohort studies (5 fair-quality,32, 34, 77, 80, 82 2 good-quality30, 31, 36, 49, 62, 67) and 1 fair-quality case-control study59 recruited screen-negative participants (AAA diameter 2.5-2.9 cm or 2.6-2.9 cm,32, 34, 59, 67, 80 <2.5 cm,82 or ≤3 cm49, 77) and administered various rescreening protocols (rescreening every 1 to 5 years with 1 to 6 repeated scans), reporting the proportion of initially screen-negative aortas that reached 5.0 or 5.5 cm at the repeat scan. This group of heterogeneous studies reported that AAA-related mortality over 5 to 12 years was rare (<3%) among participants with normal aortas (<3 cm) on the initial scan. On rescreening, few aortas (0%- 2%) grew to larger than 5 cm at 5 years,32, 34, 49, 59, 80 and 0% to 15% had progressed at 10 years.31, 77 Four studies reported no AAA ruptures or AAA-related deaths32, 49, 80, 82 at 4- to 5-year follow-up; 1 population screening program reported 2.4% ruptures at 7.9-year median follow-up.31 Overall, this heterogenous body of literature was too limited to make conclusions about the effectiveness of rescreening.
Harms of Screening
Key Question 3. What are the harms associated with 1-time and repeated screening?
Two population-based screening trials reported no statistically significant difference in 30-day operative mortality from elective surgical procedures (RR, 0.76 [95% CI, 0.40-1.45];83 RR, 0.82 [95% CI, 0.43-1.57]5) and emergency surgical procedures (RR, 1.43 [95% CI, 0.90-2.25];5 RR, 0.98 [95% CI, 0.68-1.43]83) among those invited to screening compared with those in the control group at 12.8- to 13.1-year follow-up (Table 1). All 5 screening trials reported more AAA-related operations in the invited group than in the control group, with 1.1% to 2.9% of the screened group undergoing surgical repair compared with 0.6% to 2.4% of the control group.5, 23, 57, 58, 83 The pooled data estimated significantly more procedures in the invited group compared with the control group (Peto OR, 1.44 [95% CI, 1.34-1.55]; I2 = 74%) (Figure 5). Implementing a screening program would increase the total number of operations per 1000 men by 6 (95% CI, 5-8). Elective operations were also consistently more common in the screened group (1.0%-2.8%) than in the control group (0.4%-2.2%) in all 5 trials5, 23, 57, 58, 83 (Figure 5, Table 1). Pooled analysis of these trials confirmed a higher elective operation rate in the screened group than in the control group (Peto OR, 1.75 [95% CI, 1.61-1.90]; I2 = 89%) (Figure 5, Table 1).This would increase the number of elective operations by 8 per 1000 men screened (95% CI, 6-9).
There were no RCTs assessing the harms of rescreening vs no rescreening in participants with normal-sized aortas (<3.0 cm) on initial screening. Six fair-quality cohort studies examined procedure rates in rescreened cohorts.32, 49, 59, 67, 80, 82 Five of these studies showed a low procedure rate (0%-4%) at up to 5-year follow-up;32, 49, 59, 80, 82 a single screening program reported a higher procedure rate of 10.9% at 7.8-year mean follow-up.67
Two subsamples of screening RCTs5, 22, 81, 83 and 3 small cohort studies52, 61, 87 had mixed results but generally showed no substantial differences in QOL or mood scores between screen-positive and screen-negative participants at up to 12 months’ follow-up; 1 of these RCTs (MASS) reported lower QOL scores at 6 weeks, but all scores were within age-matched population normal standards.22, 83
Benefits of Early Treatment for Small AAAs
Key Question 4. What are the effects of treatment on intermediate and health outcomes in an asymptomatic, screen-detected population with small AAAs (ie, aortic diameter of 3.0-5.4 cm)?
Four trials evaluated the effectiveness of immediate surgical repair of small aneurysms (4-5.4 cm) vs surveillance every 3 to 6 months until the aneurysm reached 5.5 cm, rapidly expanded (>1 cm/y), or became symptomatic. The Aneurysm Detection and Management trial (ADAM)51 and the UK Small Aneurysm Trial (UKSAT)74 evaluated the effectiveness of early open surgery, and the Comparison of Surveillance vs Aortic Endografting for Small Aneurysm Repair (CAESAR)29 and Positive Impact of Endovascular Options for Treating Aneurysm Early (PIVOTAL) trial69 evaluated EVAR interventions (Table 2).
The CAESAR29 and PIVOTAL trials69 terminated recruitment early because of interim analysis concluding intervention futility, but participants who had already been enrolled completed scheduled follow-up visits.
The 4 trials of early surgery found no significant differences in all-cause or AAA-specific mortality at any follow-up time between participants receiving early surgical repair vs those under surveillance (Table 2).29, 51, 69, 74 An individual patient data analysis (n = 2226) of the 2 trials of open repair additionally supported no survival benefit (adjusted hazard ratio, 0.99 [95% CI, 0.83-1.18]).37 Ruptures were rare events in all surgical trials; however, participants who underwent early open repair had a significant reduction in the rate of rupture compared with those who underwent surveillance at each follow-up interval (RR, 0.18 [95% CI, 0.04-0.81] at 4.9 years [n = 1136]; RR, 0.33 [95% CI, 0.13- 0.83] at 4.6 years [n = 1090]; RR, 0.51 [95% CI, 0.26-0.99] at 12 years [n = 1090]) (Table 2).51, 73, 74 There were only 3 ruptures in the EVAR trials, making comparisons challenging. Overall, there were more surgical interventions in the early surgery groups than in the surveillance groups undergoing mostly elective surgical procedures (Table 2).
Seven short-term drug trials (n = 1553) of antibiotics, antihypertensive medications, and mast cell stabilizers showed no overall effect on AAA growth compared with placebo. Details are provided in the full evidence report.
Harms of Early Treatment for Small AAAs
Key Question 5. What are the harms of treatment in an asymptomatic, screen-detected population with small AAAs (ie, aortic diameter of 3.0-5.4 cm)?
Both the ADAM trial and UKSAT reported no significant difference in 30-day postoperative mortality rates in the early open repair and surveillance groups (2.1% vs 1.8% in ADAM; 5.0% vs 6.3% in UKSAT) (Table 3).51, 74 The 2 largest and most contemporary registries (2011 to 2015; 2010 to 2013) capturing open repairs of small aneurysms reported a 30-day operative mortality rate within the range reported in these trials (3.1% and 3.5%) (Table 3).27, 70 Thirty-day operative mortality after EVAR in both the CAESAR and PIVOTAL trials was rare (Table 4).29, 69 The 2 largest and most contemporary registries (2011 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program [ACS NSQIP]; 2010 to 2013 in Vascunet) capturing EVAR of small aneurysms reported a 30-day operative mortality rate for EVAR of 0.7%.27, 70 The 2 oldest registries reported slightly higher mortality rates from EVAR (1.1% in Australian Safety and Efficacy Register of New Interventional Procedures–Surgical [ASERNIP-S]; 1.6% in European Collaborators on Stent/Graft Techniques for Aortic Aneurysm Repair [EUROSTAR]) (Table 4).40, 71
Only the ADAM trial reported adverse event rates for the open repair intervention and control groups, and results were mixed. The rate of 30-day readmissions was not significantly different between the surgery and surveillance groups, nor were the overall complication rates significantly different (Table 3).51 Furthermore, the event rate for total major complications was higher in the surveillance group than the early treatment group (7.6% vs 4.6%, no statistical testing reported), with a significantly higher risk of surgery-related myocardial infarction reported in the surveillance group (1.0% vs 3.8%, P = .004). The ACS NSQIP registry reported overall 30-day morbidity for open repair as approximately 69.4% at 30 days after intervention, with the most common complication being bleeding (Table 3).70
Complications were variably reported in the 2 trials of EVAR.29, 69 In the CAESAR trial, the percentage of patients with any adverse events was significantly higher at 32.4-month follow-up in the early EVAR group compared with the surveillance group (19.1% vs 5.1%, P < .01). In addition, the percentage of patients with any morbidity related to repair at 30 days was also higher in the EVAR group compared with the surveillance group (17.7% vs 6.0%, P = .01).29 Rates of any major morbidity (3.4% vs 4.7%) and 30-day endoleaks (16% vs 8.2%) were not significantly different in the early EVAR compared with the surveillance groups, but the early EVAR group had significantly more endoleaks at 1 year (12% vs 2.4%, P = .03) and significantly more reinterventions than the group undergoing surveillance (5.7% vs 0%, P = .03) (Table 4). The PIVOTAL trial reported rates of endoleaks in the early intervention and surveillance groups at 30 days after intervention (11.9% vs 10.3%) and at 1 year (26.1% vs 35.1%), but statistical testing was not reported (Table 4).
Two EVAR registries (ASERNIP-S40 and EUROSTAR71) and the 1 registry of both open repair and EVAR (ACS NSQIP)70 reported complication rates after EVAR intervention on small AAAs (Table 4). Registry data reported a composite of major or systemic complication rates for EVAR ranging from 12% to 29% at 30 days after intervention, which is consistent with trial data.29, 69-71 ASERNIP-S and ACS NSQIP reported reintervention rates within 30 days of EVAR of approximately 3%;40, 70 these rates are likewise comparable to trial data.29, 69 The ACS NSQIP reported readmission rates for small AAAs at 30-day postintervention as 6.8% after EVAR.70 Readmission rates were not reported in the trials, so these data cannot be compared with trial findings. ASERNIP-S and EUROSTAR reported the occurrence of endoleaks at 20% and 31%, respectively, at 3- to 4-year follow-up.40, 71
Eight short-term drug trials (n = 1598) reported high rates of adverse event–related discontinuation with propranolol (38% and 60% of the propranolol groups withdrew from the trials); other medications (including other antihypertensive medications [angiotensin-converting enzyme inhibitors, calcium channel blockers], antibiotics), apparently well tolerated based on few trial withdrawals, were reported in 1 to 2 studies per drug class.
Screening and Treatment Among Subpopulations
There was limited credible subpopulation information from the body of included studies. The Western Australia trial5 showed that smoking was associated with a higher risk of all-cause mortality (OR, 1.59 [95% CI, 1.47-1.72]) and AAA-related mortality (OR, 2.95 [95% CI, 1.04-8.43]) in the screened group, but no included study examined differential screening benefits by smoking status or family history (KQ1a). Subgroup analyses in the Viborg and Western Australia trials suggested that there is no differential screening effect on mortality by age.5, 58 The Chichester trial23, 76 recruited 9342 women and showed a lower prevalence of AAA in women compared with men (1.3% vs 7.6%), with most screen-detected AAAs measuring 3.0 to 3.9 cm.76, 78 There was no significant difference in AAA rupture rates among women at 10-year follow-up (0.2% in both the screened and unscreened group) or in AAA-related mortality (0.06% vs 0.04%) or all-cause mortality (10.7% vs 10.2%) at 5 years between the invited and control groups; however, the trial was underpowered. Based on 2 trials of open repair, there was no differential treatment effect on all-cause mortality by sex (KQ4a).51, 73 Registry data, however, showed a higher rate of postoperative mortality after elective repair of small AAAs in women compared with men, regardless of the surgical technique (KQ5a).27, 40
This review, performed since the previous systematic review for the USPSTF in 2014,17 included the following new data: (1) the final long-term follow-up from the Western Australia trial added to the meta-analysis confirmed prior AAA mortality benefits of screening;5 (2) 2 new small rescreening cohort studies offered little additional information to a heterogeneous literature;80, 82 (3) 3 additional pharmacotherapy trials showed no benefit in halting AAA growth;24, 63, 79 (4) 1 new population-based screening trial (VIVA) added to the meta-analysis on additional operations associated with screening confirmed previous results;57 and (5) 3 contemporary registries27, 60, 70 provided complication rates from EVAR and open repair generally comparable to those cited in the included trials.
A summary of the evidence by key question is provided in Table 5. The meta-analyses demonstrated that offering 1-time screening to men aged 65 to 75 years was associated with lower AAA-related mortality, AAA rupture, and emergency surgical procedures over 13 to 15 years of follow-up (KQ1) but do not resolve the question of all-cause mortality benefit. In terms of harms, screening for AAA was shown to expose patients to more procedures, which was primarily driven by elective operations. Overdiagnosis and overtreatment were not addressed in these trials but may be important considerations given that most screen-detected aneurysms are small.
The interest in a more targeted, high-risk approach to screening to enrich yield is particularly relevant given declines prevalence in men over the past 2 decades.67, 89-91 However, limiting screen-eligible populations to only “high-risk” populations inherently results in missed cases. Any attempt to expand screened populations (eg, extending to all men regardless of smoking history, increasing upper age threshold, adding women) would invariably increase detection of aneurysms smaller than 5.4 cm in diameter and would contribute to overdiagnosis and overtreatment. Based on US data showing that a substantial proportion of small aneurysms are repaired despite the lack of evidence of benefit over surveillance,92 the number of procedures and consequent surgical harms that may ensue as a result of broadening the eligibility for screening remains a concern.
Because the population-based screening trials almost exclusively recruited white men aged 65 to 75 years and generally did not report outcomes by subpopulation, one critical question is whether these findings can be extrapolated to other populations. In the absence of trial data, assessing generalizability requires an understanding of contextual evidence about contemporary prevalence, natural history, and treatment effectiveness.
Indirect evidence in subpopulations (older age, female sex, smoking, and family history) reveal a set of complex issues. A large proportion of AAA burden (prevalence and ruptures) occurs in older age groups.93, 94 While AAA prevalence increases with age, so do surgical complications, including mortality.95 The prevalence of AAA in women has consistently been reported to be less than in men.96, 97 However, small AAAs appear to have a higher risk of rupture25, 98-100 or rupture at a later age76, 99, 101-106 and result in higher surgical complications—including 30-day postoperative mortality rates,102-104, 107, 108 in-hospital mortality,109 major complications,104, 108, 110 and readmissions103 after elective open repair or EVAR—in women than in men. A recent model examining the effectiveness of screening women 65 years or older using contemporary assumptions111 estimated that 3900 screening invitations would be required to avoid 1 AAA-related death, which is higher than estimation in other models for men (the number needed to invite to screening was 700 for men).112
Smoking is the strongest predictor of AAA prevalence,10, 97, 100, 113, 114 growth,100 and rupture rates.100 Even with substantial declines since 1995-2002 when the screening trials were conducted,89 AAA prevalence in male smokers aged 65 to 75 years matches that of the population-based screening trials.115 Family history is associated with an increased risk of developing AAA (OR, 2.2 [95% CI, 1.6-3.2]).116 At this time, however, there is a lack of evidence to determine whether individuals with family histories exhibit differences in natural history or surgical success rates to alter the net screening benefits. Overall, because there is no direct trial evidence evaluating screening effectiveness in subpopulations and no externally validated risk assessment tools, decision analysis models populated with meta-analytic estimates of prevalence, yield, and surgical complication rates would be considered the best available evidence to date.
There are several limitations to the existing literature. The 4 large, population-based screening trials began recruiting participants during an era that predated the current widespread implementation of aggressive CVD risk-factor management and reductions in smoking. Thus, the contemporary AAA prevalence cited in Europe, and therefore the absolute benefit of screening, have declined over the intervening time. A general US population–based estimate of contemporary AAA prevalence is lacking, particularly for subpopulations, as a result of low AAA screening uptake in the United States. Furthermore, trial literature does not address the potential effect of AAA screening on CVD mortality through identification of individuals at increased CVD risk and provision of aggressive CVD risk modification.83, 117, 118 However, those identified with AAA would already be candidates for aggressive CVD risk management based on the Atherosclerotic Cardiovascular Disease Risk Algorithm’s predicted 10-year risk of greater than or equal to 7.5% or 10%, as is standard contemporary guidance in the United States.119, 120
The current review and analysis included results limited to studies that met the USPSTF fair- or good-quality criteria, per USPSTF methods.16 For 3 of the key questions (KQ2, KQ4, KQ5), there were too few studies or the studies were too clinically or statistically heterogeneous for pooling.21
Source: This article was first published in the Journal of the American Medical Association on December 10, 2019 (JAMA. 2019;322(22):2219-2238. doi:10.1001/jama.2019.17021).
Conflict of Interest Disclosures: None reported.
Funding/Support: This research was funded under contract HHSA290201500007I, Task Order 3, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).
Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.
Additional Information: A draft version of this evidence report underwent external peer review from 5 content experts (Elliot Chaikof, MD, PhD, Beth Israel Deaconess Medical Center; Giampaolo Greco, PhD, MPH, Icahn School of Medicine at Mount Sinai; Jes Lindholt, DMSci, PhD, Odense University Hospital; Janet Powell, MD, PhD, Imperial College, London; and Evan Ryer, MD, Geisinger Medical Center) and 3 federal partners: the Centers for Disease Control and Prevention, Indian Health Service, and National Institutes of Health. Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.
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102. Tomee SM, Lijftogt N, Vahl A, Hamming JF, Lindeman JHN. A registry-based rationale for discrete intervention thresholds for open and endovascular elective abdominal aortic aneurysm repair in female patients. J Vasc Surg. 2018;67(3):735-739. doi:10.1016/j.jvs.2017.07.123
103. Lowry D, Singh J, Mytton J, Tiwari A. Sex-related outcome inequalities in endovascular aneurysm repair. Eur J Vasc Endovasc Surg. 2016;52(4):518-525. doi:10.1016/j.ejvs.2016.07.083
104. Deery SE, Lancaster RT, Baril DT, et al. Contemporary outcomes of open complex abdominal aortic aneurysm repair. J Vasc Surg. 2016;63(5):1195-1200. doi:10.1016/j.jvs.2015.12.038
105. Desai M, Choke E, Sayers RD, Nath M, Bown MJ. Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men. Eur Heart J. 2016;37(46):3452-3460. doi:10.1093/eurheartj/ehw335
106. Heikkinen M, Salenius JP, Auvinen O. Ruptured abdominal aortic aneurysm in a well-defined geographic area. J Vasc Surg. 2002;36(2):291-296. doi:10.1067/mva.2002.125479
107. Ulug P, Sweeting MJ, von Allmen RS, Thompson SG, Powell JT, SWAN Collaborators. Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis. Lancet. 2017;389(10088):2482-2491. doi:10.1016/S0140-6736(17)30639-6
108. Mehta M, Byrne WJ, Robinson H, et al. Women derive less benefit from elective endovascular aneurysm repair than men. J Vasc Surg. 2012;55(4):906-913. doi:10.1016/j.jvs.2011.11.047
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Figure 1. Analytic Framework: Primary Care Screening for Abdominal Aortic Aneurysm
Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review will address to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions and outcomes. A dashed line depicts a health outcome that follows an intermediate outcome. Refer to USPSTF Procedure Manual for further details.16 AAA indicates abdominal aortic aneurysm.
Figure 2. Literature Search Flow Diagram: Primary Care Screening for Abdominal Aortic Aneurysm
Reasons for exclusion: Aim: Study aim was not relevant. Setting: Study was not conducted in a country relevant to US practice, or not conducted in, recruited from, or feasible for primary care or a health system. Population: Study was not conducted in an included population. Outcomes: Study did not have relevant outcomes or had incomplete outcomes. Intervention: Intervention was out of scope. Study design: Study did not use an included design. Comparative effectiveness: Active comparator. Quality: Study was poor quality. Publication type: Abstract-only, non-English publication. AAA indicates abdominal aortic aneurysm; KQ, key question; USPSTF, US Preventive Services Task Force.
Table 1. Characteristics and Outcomes of Abdominal Aortic Aneurysm Screening Trials
|Eligible Age (Mean), y||AAA Prevalence, %||Mean Follow-up, y||All-Cause
Mortality, RR (95% CI)a
|OR (95% CI)a||30-d Mortality After Surgery,
RR (95% CI)
Ashton et al,23
|15,382 (6040 men,
|65-80 (72.0b)||Men: 7.6
|Men: 1.0 (0.97-1.04)||Men: 0.88
Lindholt et al,58
|64-73 (67.7)||3.9||13.0||0.98 (0.95-1.02)||0.37
Thompson et al,83
|65-74 (69.2)||4.9||13.1||0.98 (0.96-1.00)||0.59
McCaul et al,5
|64-83 (72.6)||7.2||12.8||0.99 (0.97-1.01)||0.92
Lindholt and Søgaard,57
|I2, %||0.0||79.7||53.3||74.1||88.5||26.7||Not calculated||NA|
Abbreviations: AAA, abdominal aortic aneurysm; MASS, Multicenter Aneurysm Screening Study; NA, not applicable; NR, not reported; OR, odds ratio; RR, relative risk; VIVA, Viborg Vascular.
c Did not include the VIVA trial mortality data because of the inability to capture the independent contribution of AAA screening within the multicomponent screening program.
Table 2. Characteristics and Outcomes of Open and EVAR Abdominal Aortic Aneurysm Surgical Trials
|Eligible Age (Mean), y||Women, %||AAA Size for Inclusion and Surveillance, cm||Mean
|RR (95% CI)a||Participants Undergoing AAA Procedure, No. (%)|
|All-Cause Mortality||AAA Mortality||AAA Rupture||Intervention||Control|
Lederle et al,51 2002
|50-79 (68.1)||0.8||4.0-5.4||4.9||1.17 (0.95-1.44)||1.13 (0.57-2.24)||0.18 (0.04-0.81)||527 (92.6)||349 (61.6)|
Powell et al,74 2007
|60-76 (69.3)||17.5||4.0-5.5||12||0.96 (0.88-1.05)||0.67 (0.45-1.02)||
|528 (93.8)||401 (76.1)|
Ouriel et al,69 2010
|40-90 (70.5)||13.4||4.0-5.0||1.7||0.99 (0.49-1.99)||1.98 (0.18-21.72)||Not calculated||326 (89.1)||112 (30.9)|
Cao et al,29 2011
(Europe and Asia)
|50-80 (68.9)||4.2||4.1-5.4||2.7b||1.22 (0.49-3.03)||0.98 (0.06-15.52)||Not calculated||175 (96.2)||85 (47.8)|
Abbreviations: AAA, abdominal aortic aneurysm; ADAM, Abdominal Aortic Aneurysm Detection and Management; CAESAR, Comparison of Surveillance vs Aortic Endografting for Small Aneurysm Repair; EVAR, endovascular aneurysm repair; NA, not applicable; NR, not reported; PIVOTAL, Positive Impact of Endovascular Options for Treating Aneurysms Early; RR, relative risk; UKSAT, UK Small Aneurysm Trial.
Table 3. Harms Associated With Open Abdominal Aortic Aneurysm Repair, Randomized Clinical Trial and Registry Data
|Source||Mean Follow-up, y||No. of Participants Analyzed||No. (%)||Major Complications|
|30-d Mortality After Elective Repair||Reintervention Rates||Readmission Rates in 30 d|
|Randomized Clinical Trial Data|
Lederle et al,51 2002
intervention, 340 control
|Intervention: 11 (2.1)a
Control: 6 (1.8)a
|Intervention: 9 (1.7)b
Control: 4 (1.2)b
|Intervention: 108 (20.5)b
Control: 56 (16.5)b
Any major complication: 24 (4.6)
MI: 5 (1.0)c
Stroke: 3 (0.6)
Pulmonary embolism: 4 (0.8)
Powell et al,74 2007
|12||915 (526 Intervention, 389 control)||Intervention: 26 (5.0)
Control: 25 (6.3)
|NR||Intervention: 30 (6.3)
Overbey et al,70
|NR||705||25 (3.5)||64 (9.1)||44 (6.2)||MI: 24 (3.4)
Stroke: 5 (0.7)
Pulmonary embolism: 3 (0.4)
Overall morbidity within 30 d of surgery: 69.4%
Bleeding complications: 460 (65.2)
Budtz-Lilly et al,27
Abbreviations: AAA, abdominal aortic aneurysm; ACS NSQIP: American College of Surgeons National Surgical Quality Improvement Program; ADAM, Abdominal Aortic Aneurysm Detection and Management study; MI, myocardial infarction; NR, not reported; UKSAT, UK Small Aneurysm Trial.
a Operative mortality associated with the repair of unruptured AAA.
b Follow-up timing NR.
c P < 0.05.
d Intervention group: From 1-year follow-up data; the use of bifurcated grafts (12/30 [40%]) was associated with a 2-fold increase in the risk of reoperation (P = 0.03).
e Defined as hospital death or death within 30 days of surgery.
Table 4. Harms Associated With EVAR Abdominal Aortic Aneurysm Repair, Randomized Clinical Trial and Registry Data
|Source||Mean Follow-up, y||No. of Participants Analyzed||No. (%)||Major Complications Within 30 d|
|30-d Mortality After Elective Repair||Rates||Endoleaks|
in 30 Days
|At 30 d||At 1 y|
|Randomized Clinical Trial Data|
Cao et al,29 2011
|2.6a||260 (175 intervention, 85 control)||Intervention: 1 (0.6)
|Intervention: 10 (5.7)b
Control: 0 (0)b
|Intervention: 28 (16.0)c
Control: 7 (8.2)c
|Intervention: 21 (12.0)c
Control: 2 (2.4)c
Any major morbidity: 6 (3.4)
Ouriel et al,69 2010
|12||431 (322 intervention, 109 control)||Intervention: 1 (0.3)
Control: 1 (0.9)
|Intervention: 12 (3.7)d
Control: 5 (4.6)d
|20 (4.6)e||Intervention: 36 (11.9)
Control: 10 (10.3)
|Intervention: 72 (26.1)
Control: 30 (35.1)
Serious cardiac event: 17 (5.3)
Serious pulmonary event: 4 (1.2)
Serious renal event: 6 (1.9)
Overbey et al,70
|NR||4471||31 (0.7)||150 (3.4)||304 (6.8)||NR||NR||Acute renal failure: 15 (0.3)
Sepsis: 20 (0.4)
Septic shock: 6 (0.1)
Cardiac arrest: 14 (0.3)
MI: 46 (1.0);
Pulmonary embolism: 5 (0.1)
Stroke: 12 (0.3)
Overall morbidity within 30 d of surgery: 11.4%
Golledge et al,40
|3.2a||478||5 (1.1)||13 (3)f||NR||46 (9.6)||97 (20.3)g||Significant postoperative complications reported in 138 (29.0); 72 systemic complications noted in 64 (13.4) of patients|
et al,71 2004
|1.7||1962||31 (1.6)||NR||NR||NR||NRh||30-d systemic complications combined: 235 (12.0)
Cardiac: 55 (2.8)d
Pulmonary: 31 (1.6)d
Early procedure or device-related: 57 (2.9)d
|Vascular Study Group of New England
Lo et al,60 2013
|1.0||1336||Men: 7 (0.7)
Women: 4 (1.1)
Budtz-Lilly et al,27
Abbreviations: AAA, abdominal aortic aneurysm; ACS NSQIP, American College of Surgeons National Surgical Quality Improvement Program; ASERNIP-S, Australian Safety and Efficacy Register of New Interventional Procedures–Surgical; CAESAR, Comparison of Surveillance vs Aortic Endografting for Small Aneurysm Repair; EVAR, endovascular aneurysm repair; MI, myocardial infarction; NR, not reported; PIVOTAL, Positive Impact of Endovascular Options for Treating Aneurysms Early.
b P < 0.05.
c Denominator is patients who received EVAR: 171 in intervention group (at 1 year, 19 [10.9%] with type 2, 1 [0.6%] with type 4, 1 [0.6%] unknown) and 71 in the control group (at 1 year, 2 [2.4%] with type 2).
d Follow-up timing NR.
e Group not specified for readmission rates.
f Reinterventions 30 or fewer days after surgery; for 30 or more days after surgery, 50 patients underwent 72 additional interventions by open repair (20 times in 16 patients [5 had an EVAR procedure]).
g Endoleak on follow-up imaging 30 or more days after procedure.
h At 4 years: 5.3% (type I proximal), 11.3% (type I distal), 14.4% (type III).
i Defined as hospital death or death within 30 days of surgery.
Table 5. Summary of Evidence
|Subpopulation||No. of Studies
(No. of Observations)
|Summary of Findings||Consistency and Precision||Other Limitations||Strength of Evidence||Applicability|
|KQ1: Benefits of Screening|
|4 (124,929)||Invitation for 1-time screening in men ≥65 y was associated with a 35% reduction in AAA-related mortality, 38% reduction in AAA rupture rate, and a 43% reduction in the number of emergency operations but no statistically significant difference in all-cause mortality at 12- to 15-y follow-up||Reasonably consistent; reasonably precise||None||Moderate to high||These population-based screening trials were set in the 1990s in mostly white men aged 65 to 75 y; since that time, AAA prevalence has declined along with smoking prevalence, and medical management of CVD has changed|
|KQ1a: Benefits of Screening Among Subpopulations|
|Age||2 (51,119)||The Viborg and Western Australia population-based screening trials reported subanalyses with substantial limitations suggesting no differential screening effect based on age||Consistent; imprecise||Subanalyses not prespecified, stratified at randomization to ensure baseline comparability, adjusted for confounders, or powered to detect subgroup differences; no heterogeneity testing was performed||Low||Both trials were conducted in mostly white older men|
|Sex||1 (9342)||There was no significant difference in AAA rupture rate at 10-y follow-up or in mortality (both AAA-related and all-cause) at 5 y between the invited and control groups
Most AAA ruptures occur at ages ≥80 y in women
|Consistency NA (1 study); imprecise||Underpowered for health outcomes||Low||Population was older white women in Chichester, United Kingdom|
|Smoking||1 (19,249)||Results showed that smoking was associated with a higher risk of all-cause mortality (OR, 1.59 [95% CI, 1.47-1.72]) and AAA-related mortality (OR, 2.95 [95% CI, 1.04-8.43]) in the screened group of men aged 64-83 y
Trend was more pronounced in the group aged 65-74 y; however, no formal analysis was performed to explore if there is a differential screening effect based on smoking status
|Consistency NA (1 study); imprecise||Subanalyses not prespecified or powered to detect subgroup differences; no heterogeneity testing performed to determine if there is modification in the effectiveness of screening among smokers||Low||Trial was conducted in mostly white older men|
|KQ2: Benefits of Rescreening|
|Entire study population||8 (8018)||Studies rescreened participants with various rescreening protocols (rescreening annually to 5 y with 1 to 6 repeated scans), demonstrating that AAA-related mortality over 5 to 12 y is rare (<3%) among those with normal aortas (<3 cm) on the initial scan
On rescreening, few aortas grew to >5 or ≥5.5 cm (0%-2.2% at 5 y; 0%-15% had progressed at 10 y)
Four studies reported no AAA ruptures or AAA-related deaths at 4- to 5-y follow-up; 1 study reported 2.4% ruptures at 7.9-y median follow-up
|Inconsistent; imprecise||Heterogeneous rescreening protocols
A small number of participants with normal aortas were included in these studies; all but a single study was exclusively in men; there are no matched controls in most studies; the primary focus of most studies was growth rate, as the follow-up time for most studies was 5 y, a time frame too short to expect the development of AAA-related health outcomes
|Low||Mostly men (only 1 trial conducted in women)
All but 1 trial conducted outside of the United States
|KQ2a: Benefits of Rescreening Among Subpopulations|
|Sex||1 (33); remaining 7 KQ2 studies in men||One small study in women was too small to compare with other rescreening studies in men||Consistency NA; imprecise||Few studies reporting outcomes by subpopulation; most studies did not report if subgroup analyses were prespecified, and studies tested numerous risk factors
Overall rescreening literature limited by lack of adequate reporting; heterogeneity of study rescreening protocols; short follow-up times with focus on growth rates rather than health outcomes
|Low||Small study of women conducted outside of the United States|
|Smoking||3 (4706)||Two studies reported multiregression analyses suggesting that current smoking is an independent risk factor for the development of AAA at rescreening, and another univariate analysis in a study of solely women showed a similar trend for smoking; however, the number developing AAAs over the rescreening interval was small||Consistent; imprecise||None||Low||Studies conducted in mostly men|
|KQ3: Harms of Screening|
|Entire study population||5 (175,085)||More procedures in the invited group compared with the control group (5 studies; Peto OR, 1.44 [95% CI, 1.34-1.55]), largely driven by elective operations (Peto OR, 1.75 [95% CI, 1.61-1.90])
There was no statistically significant difference in 30-d operational mortality rates in the invited vs control groups for either elective surgical procedures or emergency surgical procedures at 12- to 15-y follow-up
|Consistent; reasonably precise||None||Moderate||Trials were conducted in mostly white older men|
|KQ3a: Harms of Screening Among Subpopulations|
|Age||1 (19,571)||Single population-based screening trial reports no significant difference in the number of elective operations and lower 30-d operative mortality after elective and emergency surgery in the younger age subset (65-74 y) compared with entire trial population (64-83 y)||Consistent (1 trial NA); imprecise||Subanalyses not prespecified, stratified at randomization to ensure baseline comparability, adjusted for confounders, or powered to detect subgroup differences; no heterogeneity testing performed||Low||Trials were conducted in mostly white older men|
|KQ4: Benefits of Early Treatment|
|Open vs surveillance (entire study population)||2 (2226)||No significant difference in all-cause mortality, AAA-related mortality; reduction in rupture seen with early open surgery compared with surveillance for small AAAs||Consistent; imprecise||Only 2 studies
No differentiation of sizes between 4-5.4 cm
|Moderate||Trials primarily recruited male patients with small AAAs (4-5.4 cm)|
|EVAR vs surveillance (entire study population)||2 (1088)||No significant difference in all-cause or AAA-related mortality with early EVAR compared with surveillance for small AAA||Consistent; imprecise||Both trials stopped early at interim analysis because of futility||Moderate||Trials primarily recruited male patients with small AAAs (4-5.4 cm)|
|Pharmacotherapy vs placebo (entire study population)||7 (1553)||Drug trials of antibiotics, antihypertensive medications, and a mast cell stabilizer showed no overall effect on AAA growth compared with placebo||Consistency NA (different drug classes); imprecise||One to 2 trials for each medication; follow-up times too short to expect development of AAA-related events or changes in health outcomes (all-cause mortality, AAA-related mortality, rupture)||Low||Studies were predominantly conducted in male patients with small AAAs
All trials were conducted outside of the United States
|KQ4a: Benefits of Early Treatment Among Subpopulations|
|Open vs surveillance by age and sex||2 (2226)||Individual patient data meta-analysis available pooling the 2 early open vs surveillance trials (ADAM and UKSAT) with 5- to 8-y follow-up reported no differential all-cause mortality effect by sex
The 2 trials reported no differential all-cause mortality treatment effect by age at 5- and 12-y follow-up; 1 of these trials (UKSAT) reported no significant difference in all-cause mortality by smoking status; this subanalysis did not address differential mortality effect of early surgery by smoking status
No data on family history or race
|Unknown consistency; imprecise||Subanalyses by age: 1 trial did not report interaction testing results
Subanalyses by sex: both prespecified analyses, 1 trial did not adjust for confounders or report interaction testing
|Low||Participants were men and women with small AAAs; analyses were separated by older and younger participants (reported in 5- to 10-y age strata), with and without a smoking history|
|EVAR vs surveillance||No studies||NA||NA||NA||NA||NA|
|Pharmacotherapy by age and smoking||Age: 1 (552)
Smoking: 1 (32)
|None of the pharmacotherapy trials report health outcomes by subgroup
One small doxycycline trial and 1 propranolol trial performed limited subgroup analyses, which do not support a treatment effect modification by age or smoking history
|Consistency NA (single trial for each medication); imprecise||Too few studies
Available analyses would be considered exploratory at best, particularly given that the subgroup methodologies were of low quality (no prespecification of analysis, adjustment for confounders, or interaction testing), and overall trial results do not support a AAA growth benefit
|KQ5: Harms of Early Treatment|
|Open vs surveillance||5 (21,298)||Two trials of early open repair vs surveillance reported a 50% higher rate of procedures in the early intervention group with no significant difference in 30-d operative mortality
Readmission rates at 30 d were not significantly different; major surgical complications were lower in the early intervention group
QOL results were mixed but generally showed declines in both the early surgery and surveillance groups over time, with no statistically significant difference between the groups up to 1 to 2 y; only the ADAM trial showed higher general health scores in the early repair group in the first 2 y that did not persist over time
One trial reported an increased incidence of impotence in the early repair group at up to 4 y
Registry harms data were generally comparable to the 2 trials with the exception of reintervention rates, which were higher in the registries compared with the ADAM trial
|Reasonably consistent for procedures and 30-d operative mortality; consistency NA for other complications (only reported in 1 trial)
Reasonably precise for procedures; 30-d mortality and complications imprecise
|Surgical morbidity complications not well reported||Moderate||Registry data from both national and international sources; contemporary|
|EVAR vs surveillance||7 (22,600)||Two trials of early EVAR vs surveillance reported approximately 100% more procedures in the early intervention group and rare 30-d operative mortality rates between the groups
In the CAESAR trial, the early intervention group had a higher percentage of patients with any adverse events (19% vs 5%, P < 0.01), any morbidity related to repair at 30 d (18% vs 6%, P = 0.01), endoleaks at 1 y (12% vs 3%, P = 0.028), and reinterventions (6% vs 0%, P = 0.03), but rates of any major morbidity over the trial duration were not significantly different (3.3% vs 2.8%, P = 0.99)
Conversely, PIVOTAL largely reported no significant difference in rates of adverse events at 30 d (12% vs 10%) and 1 y (26% vs 35%) and reinterventions (3.7% vs 4.6%)
Reported complication rates from registry data were generally comparable with those rates reported in the above trials for 30-d operative mortality and reinterventions
|Consistent for procedures, 30-d operative mortality, reinterventions, major morbidity; precise for procedures, 30-d mortality, reinterventions||Individual postoperative complications and major morbidities variably reported||Moderate||Registry data from both national and international sources; contemporary|
|Pharmacotherapy vs placebo||8 (1598)||With the exception of the 2 propranolol trials reporting high adverse events–related discontinuation rates (38% and 60% of the propranolol groups withdrew from the trials), other medications (including other antihypertensive medications [ACE inhibitors, calcium channel blocker] and antibiotics) appear to be well tolerated based on few trial withdrawals reported from 1 to 2 studies per drug class||Propranolol: consistent, imprecise
Doxycycline: consistent, imprecise
Other drugs: NA for consistency (1 trial for each drug); imprecise
|One to 2 trials per drug class with limited harms reporting||Low||Predominantly male population with small AAAs
All trials conducted outside of the United States
|KQ5a: Harms of Early Treatment Among Subpopulations|
|Sex||3 (14,424)||Scant data on harms in subpopulations
No trial data available to examine harms in subpopulations
Existing evidence shows higher 30-d operative mortality and secondary complications in women compared with men for both EVAR and open repair
No information available for other subpopulations
|Consistent; imprecise||Few registries and nontrial data; few outcomes (mostly 30-d operative mortality)||Moderate||Registry data from both national and international sources; contemporary|
Abbreviations: AAA, abdominal aortic aneurysm; ACE, angiotensin-converting enzyme; ADAM, Abdominal Aortic Aneurysm Detection and Management; CAESAR, Comparison of Surveillance Versus Aortic Endografting for Small Aneurysm Repair; CVD, cardiovascular disease; EVAR, endovascular aneurysm repair; KQ, key question; NA, not applicable; OR. odds ratio; PIVOTAL, Positive Impact of Endovascular Options for Treating Aneurysms Early; QOL, quality of life; UKSAT, UK Small Aneurysm Trial.
Internet Citation: Evidence Summary: Abdominal Aortic Aneurysm: Screening . U.S. Preventive Services Task Force. December 2019.