Pinar Ulug1, Janet T Powell1, Melissa Ashley-Marie Martinez2, David J Ballard3, Giovanni Filardo4,5. 1. Vascular Surgery Research Group, Imperial College London, London, UK. 2. Department of Neurology, University of Arizona, Phoenix, AZ, USA. 3. Department of Health Policy and Management, UNC Gillings School of Global Public Health, North Carolina, USA. 4. Robbins Institute for Health Policy and Leadership, Baylor University, Waco, USA. 5. Department of Statistical Science, Southern Methodist University, Dallas, USA.
Abstract
BACKGROUND: An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the major abdominal artery. Some AAAs present as emergencies and require surgery; others remain asymptomatic. Treatment of asymptomatic AAAs depends on many factors, but the size of the aneurysm is important, as risk of rupture increases with aneurysm size. Large asymptomatic AAAs (greater than 5.5 cm in diameter) are usually repaired surgically; very small AAAs (less than 4.0 cm diameter) are monitored with ultrasonography. Debate continues over the roles of early repair versus surveillance with repair on subsequent enlargement in people with asymptomatic AAAs of 4.0 cm to 5.5 cm diameter. This is the fourth update of the review first published in 1999. OBJECTIVES: To compare mortality and costs, as well as quality of life and aneurysm rupture as secondary outcomes, following early surgical repair versus routine ultrasound surveillance in people with asymptomatic AAAs between 4.0 cm and 5.5 cm in diameter. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, two other databases, and two trials registers to 10 July 2019. We handsearched conference proceedings and checked reference lists of relevant studies. SELECTION CRITERIA: We included randomised controlled trials where people with asymptomatic AAAs of 4.0 cm to 5.5 cm were randomly allocated to early repair or imaging-based surveillance at least every six months. Outcomes had to include mortality or survival. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, which were cross-checked by other team members. Outcomes were mortality, costs, quality of life, and aneurysm rupture. For mortality, we estimated risk ratios (RR) (endovascular aneurysm repair only), hazard ratios (HR) (open repair only), and 95% confidence intervals (CI) based on Mantel-Haenszel Chi2 statistics at one and six years (open repair only) following randomisation. MAIN RESULTS: We found no new studies for this update. Four trials with 3314 participants fulfilled the inclusion criteria. Two trials compared early open repair with surveillance and two trials compared early endovascular repair (EVAR) with surveillance. We used GRADE to access the certainty of the evidence for mortality and cost, which ranged from high to low. We downgraded the certainty in the evidence from high to moderate and low due to risk of bias concerns and imprecision (some outcomes were only reported by one study). All four trials showed an early survival benefit in the surveillance group (due to 30-day operative mortality with repair) but no evidence of differences in long-term survival. One study compared early open repair with surveillance with an adjusted HR of 0.88 (95% CI 0.75 to 1.02, mean follow-up 10 years; HR 1.21, 95% CI 0.95 to 1.54, mean follow-up 4.9 years). Pooled analysis of participant-level data from the two trials comparing early open repair with surveillance (maximum follow-up seven to eight years) showed no evidence of a difference in survival (propensity score-adjusted HR 0.99, 95% CI 0.83 to 1.18; 2226 participants; high-certainty evidence). This lack of treatment effect did not vary to three years by AAA diameter (P = 0.39), participant age (P = 0.61), or for women (HR 0.84, 95% CI 0.62 to 1.11). Two studies compared EVAR with surveillance and there was no evidence of a survival benefit for early EVAR at 12 months (RR 1.92, 95% CI 0.73 to 5.06; 846 participants; low-certainty evidence). Two trials reported costs. The mean UK health service costs per participant over the first 18 months after randomisation were higher in the open repair surgery than the surveillance group (GBP 4978 in the repair group versus GBP 3914 in the surveillance group; mean difference (MD) GBP 1064, 95% CI 796 to 1332; 1090 participants; moderate-certainty evidence). There was a similar difference after 12 years. The mean USA hospital costs for participants at six months after randomisation were higher in the EVAR group than in the surveillance group (USD 33,471 with repair versus USD 5520 with surveillance; MD USD 27,951, 95% CI 25,156 to 30,746; 614 participants; low-certainty evidence). After four years, there was no evidence of a difference in total medical costs between groups (USD 48,669 with repair versus USD 46,112 with surveillance; MD USD 2557, 95% CI -8043 to 13,156; 614 participants; low-certainty evidence). All studies reported quality of life but used different assessment measurements and results were conflicting. All four studies reported aneurysm rupture. There were very few ruptures reported in the trials of EVAR versus surveillance up to three years. In the trials of open surgery versus surveillance, there were ruptures to at least six years and there were more ruptures in the surveillance group, but most of these ruptures occurred in aneurysms that had exceeded the threshold for surgical repair. AUTHORS' CONCLUSIONS: There was no evidence of an advantage to early repair for small AAA (4.0 cm to 5.5 cm), regardless of whether open repair or EVAR is used and, at least for open repair, regardless of patient age and AAA diameter. Thus, neither early open nor early EVAR of small AAAs is supported by currently available evidence. Long-term data from the two trials investigating EVAR are not available, so, we can only draw firm conclusions regarding outcomes after the first few years for open repair. Research regarding the risks related to and management of small AAAs in ethnic minorities and women is urgently needed, as data regarding these populations are lacking.
BACKGROUND: An abdominal aortic aneurysm (AAA) is an abnormal ballooning of the major abdominal artery. Some AAAs present as emergencies and require surgery; others remain asymptomatic. Treatment of asymptomatic AAAs depends on many factors, but the size of the aneurysm is important, as risk of rupture increases with aneurysm size. Large asymptomatic AAAs (greater than 5.5 cm in diameter) are usually repaired surgically; very small AAAs (less than 4.0 cm diameter) are monitored with ultrasonography. Debate continues over the roles of early repair versus surveillance with repair on subsequent enlargement in people with asymptomatic AAAs of 4.0 cm to 5.5 cm diameter. This is the fourth update of the review first published in 1999. OBJECTIVES: To compare mortality and costs, as well as quality of life and aneurysm rupture as secondary outcomes, following early surgical repair versus routine ultrasound surveillance in people with asymptomatic AAAs between 4.0 cm and 5.5 cm in diameter. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, two other databases, and two trials registers to 10 July 2019. We handsearched conference proceedings and checked reference lists of relevant studies. SELECTION CRITERIA: We included randomised controlled trials where people with asymptomatic AAAs of 4.0 cm to 5.5 cm were randomly allocated to early repair or imaging-based surveillance at least every six months. Outcomes had to include mortality or survival. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data, which were cross-checked by other team members. Outcomes were mortality, costs, quality of life, and aneurysm rupture. For mortality, we estimated risk ratios (RR) (endovascular aneurysm repair only), hazard ratios (HR) (open repair only), and 95% confidence intervals (CI) based on Mantel-Haenszel Chi2 statistics at one and six years (open repair only) following randomisation. MAIN RESULTS: We found no new studies for this update. Four trials with 3314 participants fulfilled the inclusion criteria. Two trials compared early open repair with surveillance and two trials compared early endovascular repair (EVAR) with surveillance. We used GRADE to access the certainty of the evidence for mortality and cost, which ranged from high to low. We downgraded the certainty in the evidence from high to moderate and low due to risk of bias concerns and imprecision (some outcomes were only reported by one study). All four trials showed an early survival benefit in the surveillance group (due to 30-day operative mortality with repair) but no evidence of differences in long-term survival. One study compared early open repair with surveillance with an adjusted HR of 0.88 (95% CI 0.75 to 1.02, mean follow-up 10 years; HR 1.21, 95% CI 0.95 to 1.54, mean follow-up 4.9 years). Pooled analysis of participant-level data from the two trials comparing early open repair with surveillance (maximum follow-up seven to eight years) showed no evidence of a difference in survival (propensity score-adjusted HR 0.99, 95% CI 0.83 to 1.18; 2226 participants; high-certainty evidence). This lack of treatment effect did not vary to three years by AAA diameter (P = 0.39), participant age (P = 0.61), or for women (HR 0.84, 95% CI 0.62 to 1.11). Two studies compared EVAR with surveillance and there was no evidence of a survival benefit for early EVAR at 12 months (RR 1.92, 95% CI 0.73 to 5.06; 846 participants; low-certainty evidence). Two trials reported costs. The mean UK health service costs per participant over the first 18 months after randomisation were higher in the open repair surgery than the surveillance group (GBP 4978 in the repair group versus GBP 3914 in the surveillance group; mean difference (MD) GBP 1064, 95% CI 796 to 1332; 1090 participants; moderate-certainty evidence). There was a similar difference after 12 years. The mean USA hospital costs for participants at six months after randomisation were higher in the EVAR group than in the surveillance group (USD 33,471 with repair versus USD 5520 with surveillance; MD USD 27,951, 95% CI 25,156 to 30,746; 614 participants; low-certainty evidence). After four years, there was no evidence of a difference in total medical costs between groups (USD 48,669 with repair versus USD 46,112 with surveillance; MD USD 2557, 95% CI -8043 to 13,156; 614 participants; low-certainty evidence). All studies reported quality of life but used different assessment measurements and results were conflicting. All four studies reported aneurysm rupture. There were very few ruptures reported in the trials of EVAR versus surveillance up to three years. In the trials of open surgery versus surveillance, there were ruptures to at least six years and there were more ruptures in the surveillance group, but most of these ruptures occurred in aneurysms that had exceeded the threshold for surgical repair. AUTHORS' CONCLUSIONS: There was no evidence of an advantage to early repair for small AAA (4.0 cm to 5.5 cm), regardless of whether open repair or EVAR is used and, at least for open repair, regardless of patient age and AAA diameter. Thus, neither early open nor early EVAR of small AAAs is supported by currently available evidence. Long-term data from the two trials investigating EVAR are not available, so, we can only draw firm conclusions regarding outcomes after the first few years for open repair. Research regarding the risks related to and management of small AAAs in ethnic minorities and women is urgently needed, as data regarding these populations are lacking.
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