Rupture Rate of Large Abdominal Aortic Aneurysms in Patients Refusing or Unfit for Elective Repair

Lederle, Frank A.; Johnson, Gary R.; Wilson, Samuel E.; Ballard, David J.; Jordan, William D.; Blebea, John; Littooy, Fred N.; Freischlag, Julie A.; Bandyk, Dennis F.; Rapp, Joseph H.; Salam, Atef A.

doi:10.1001/jama.287.22.2968

Cited by 527 publications

(253 citation statements)

References 17 publications

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“…For AAA diameters outside that included in the RESCAN project, information on AAA growth and risk of rupture was taken from other previously published studies. [47][48][49][50] DATA SOURCES NIHR Journals Library www.journalslibrary.nihr.ac.uk…”

Section: Aneurysm Growth and Risk Of Rupturementioning

confidence: 99%

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Calculating when elective abdominal aortic aneurysm repair improves survival for individual patients: development of the Aneurysm Repair Decision Aid and economic evaluation

Grant

Sperrin

Carlson

et al. 2015

Health Technology Assessment

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BackgroundAbdominal aortic aneurysm (AAA) repair aims to prevent premature death from AAA rupture. Elective repair is currently recommended when AAA diameter reaches 5.5 cm (men) and 5.0 cm (women). Applying population-based indications may not be appropriate for individual patient decisions, as the optimal indication is likely to differ between patients based on age and comorbidities.ObjectiveTo develop an Aneurysm Repair Decision Aid (ARDA) to indicate when elective AAA repair optimises survival for individual patients and to assess the cost-effectiveness and associated uncertainty of elective repair at the aneurysm diameter recommended by the ARDA compared with current practice.Data sourcesThe UK Vascular Governance North West and National Vascular Database provided individual patient data to develop predictive models for perioperative mortality and survival. Data from published literature were used to model AAA growth and risk of rupture. The cost-effectiveness analysis used data from published literature and from local and national databases.MethodsA combination of systematic review methods and clinical registries were used to provide data to populate models and inform the structure of the ARDA. Discrete event simulation (DES) was used to model the patient journey from diagnosis to death and synthesised data were used to estimate patient outcomes and costs for elective repair at alternative aneurysm diameters. Eight patient clinical scenarios (vignettes) were used as exemplars. The DES structure was validated by clinical and statistical experts. The economic evaluation estimated costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) from the NHS, social care provider and patient perspective over a lifetime horizon. Cost-effectiveness acceptability analyses and probabilistic sensitivity analyses explored uncertainty in the data and the value for money of ARDA-based decisions. The ARDA outcome measures include perioperative mortality risk, annual risk of rupture, 1-, 5- and 10-year survival, postoperative long-term survival, median life expectancy and predicted time to current threshold for aneurysm repair. The primary economic measure was the ICER using the QALY as the measure of health benefit.ResultsThe analysis demonstrated it is feasible to build and run a complex clinical decision aid using DES. The model results support current guidelines for most vignettes but suggest that earlier repair may be effective in younger, fitter patients and ongoing surveillance may be effective in elderly patients with comorbidities. The model adds information to support decisions for patients with aneurysms outside current indications. The economic evaluation suggests that using the ARDA compared with current guidelines could be cost-effective but there is a high level of uncertainty.LimitationsLack of high-quality long-term data to populate all sections of the model meant that there is high uncertainty about the long-term clinical and economic consequences of repair. Modelling assumptions were necessary and the developed survival models require external validation.ConclusionsThe ARDA provides detailed information on the potential consequences of AAA repair or a decision not to repair that may be helpful to vascular surgeons and their patients in reaching informed decisions. Further research is required to reduce uncertainty about key data, including reintervention following AAA repair, and assess the acceptability and feasibility of the ARDA for use in routine clinical practice.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Aneurysm Growth and Risk Of Rupturementioning

confidence: 99%

“…47 Extrapolation assumes rupture probability doubles every 0.5 cm size increase up to 6.5 cm, then switches to the given values for 7.0 cm and 8.0 cm. 49,50 The current data we use are shown in Table 19.…”

Section: Data Sources and Variable Estimationmentioning

confidence: 99%

Calculating when elective abdominal aortic aneurysm repair improves survival for individual patients: development of the Aneurysm Repair Decision Aid and economic evaluation

Grant

Sperrin

Carlson

et al. 2015

Health Technology Assessment

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“…About a quarter of untreated AAAs end with rupture [5], which has a mortality rate of 70–80% [6]. The risk of rupture increases with an increasing diameter of the aneurysm [7]. The epidemiological profile of AAA seems to be changing.…”

mentioning

confidence: 99%

Asymptomatic Abdominal Aortic Aneurysms Show Histological Signs of Progression: A Quantitative Histochemical Analysis

Eberlová¹,

Tonar²,

Witter

et al. 2012

Pathobiology

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Objective: Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology. Methods: In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5–7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples. Results: Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular. Conclusion: Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

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“…39 Similarly, the 5-year overall cumulative rupture rate of incidentally diagnosed AAAs in population-based samples is 25-40% for aneurysms of > 5.0 cm diameter and 1-7% for aneurysms of 4.0-5.0 cm in diameter. 40,41 Rupture rates have been found to be doubled in current smokers compared with ex-smokers or non-smokers (p = 0.001) and to increase with mean arterial pressure (per 10 mmHg) (p = 0.001).…”

Section: Rupture Rates Of Small Abdominal Aortic Aneurysmsmentioning

confidence: 98%

An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled trial (AARDVARK)

Kiru

Bicknell

Falaschetti

et al. 2016

Health Technol Assess

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BACKGROUND: Although data are inconsistent, angiotensin-converting enzyme inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal aortic aneurysm (AAA) rupture in analysis of administrative databases. OBJECTIVES: (1) To investigate whether or not the ACE-I perindopril (Coversyl arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood pressure (BP)-independent effects of perindopril on small AAA growth and to compare the repeatability of measurement of internal and external aneurysm diameters. DESIGN: A three-arm, multicentre, single-blind, randomised placebo-controlled trial. SETTING: Fourteen hospitals in England. PARTICIPANTS: Men or women aged ≥ 55 years with an AAA of 3.0-5.4 cm in diameter by internal or external measurement according to ultrasonography and who met the trial eligibility criteria. INTERVENTIONS: Patients were randomised to receive 10 mg of perindopril arginine daily, 5 mg of the calcium channel blocker amlodipine daily or placebo daily. MAIN OUTCOME MEASURES: The primary outcome was AAA diameter growth using external measurements in the longitudinal plane, which in-trial studies suggested was the preferred measure. Secondary outcome measures included AAA rupture, AAA repair, modelling of the time taken for the AAA to reach the threshold for intervention (5.5 cm) or referral for surgery, tolerance of study medication (measured by compliance, adverse events and quality of life) and a comparison of the repeatability of measures of internal and external AAA diameter. Patients were followed up every 3-6 months over 2 years. RESULTS: In total, 227 patients were recruited and randomised into the three groups, which were generally well matched at baseline. Multilevel modelling was used to determine the maximum likelihood estimates for AAA diameter growth. No significant differences in the estimates of annual growth were apparent [1.68 (standard error 0.02) mm, 1.77 (0.02) mm and 1.81 (0.02) mm in the placebo, perindopril and amlodipine groups, respectively]. Similarly, no significant differences in the slopes of modelled growth over time were apparent between perindopril and placebo (p = 0.78) or between perindopril and amlodipine (p = 0.89). The results were essentially unaffected by adjustment for potential confounders. Compliance, measured by pill counts, was good throughout (> 80% at all visit time points). There were no significant in-trial safety concerns. Six patients withdrew because of adverse events attributed to the study medications (n = 2 perindopril, n = 4 amlodipine). No patients ruptured their AAA and 27 underwent elective surgery during the trial (n = 9 placebo, n = 10 perindopril, n = 8 amlodipine). CONCLUSIONS: We were unable to demonstrate a significant impact of perindopril compared with placebo or amlodipine on small AAA growth over a 2-year period. Furthermore, there were no differences in the times to reach a diameter of 5.5 cm or undergo surgery among the three groups. Perindopril and amlodipine were well tolerated by this population. ...

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Rupture Rate of Large Abdominal Aortic Aneurysms in Patients Refusing or Unfit for Elective Repair

Cited by 527 publications

References 17 publications

Calculating when elective abdominal aortic aneurysm repair improves survival for individual patients: development of the Aneurysm Repair Decision Aid and economic evaluation

Calculating when elective abdominal aortic aneurysm repair improves survival for individual patients: development of the Aneurysm Repair Decision Aid and economic evaluation

Asymptomatic Abdominal Aortic Aneurysms Show Histological Signs of Progression: A Quantitative Histochemical Analysis

An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled trial (AARDVARK)

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