444 results found
Sweeting MJ, Patel R, Powell JT, et al., 2017, Endovascular repair of abdominal aortic aneurysm in patients physically ineligible for open repair: very long-term follow-up in the EVAR-2 randomized controlled trial, Annals of Surgery, Vol: 266, Pages: 713-719, ISSN: 0003-4932
OBJECTIVE: The aim of the study was to compare long-term total and aneurysm-related mortality in physically frail patients with abdominal aortic aneurysm (AAA) randomized to either early endovascular aneurysm repair (EVAR) or no-intervention. SUMMARY BACKGROUND DATA: EVAR-2 remains the sole randomized trial to identify whether EVAR reduces mortality in patients physically ineligible for open repair. METHODS: Between September 1999 and August 2004, 404 patients from 33 centers in the United Kingdom aged ≥60 years with AAA >5.5 cm in diameter were randomized 1:1 using computer-generated sequences of randomly permuted blocks stratified by center to receive either EVAR (197) or no-intervention (207). The primary analysis compared total and aneurysm-related deaths in groups until June 30, 2015 (mean, 12.0 yrs; maximum 14.1 yrs). RESULTS: Mean follow-up until death or censoring was 4.2 years. There were 187 deaths (22.6 per 100 person-yrs) in the EVAR group and 194 (22.1 per 100 person-yrs) in the no-intervention group. By 12 years of follow-up the estimated survival was 5.3% [95% confidence interval (CI), 2.6-9.2] in the EVAR group and 8.5% (95% CI, 5.2-12.9) in the no-intervention group; there was no significant difference in life expectancy between the groups (both 4.2 yrs; P = 0.97). However, overall aneurysm-related mortality was significantly lower in the EVAR group [3.3 deaths per 100 person-yrs compared with 6.5 deaths per 100 person-yrs in the no-intervention group, adjusted hazard ratio 0.55 (95% CI, 0.34-0.91; P = 0.019)]. Patients surviving beyond 8 years were younger, with higher body mass index, estimated glomerular filtration rate, and forced expiratory volume in 1 second. CONCLUSIONS: EVAR does not increase overall life expectancy in patients ineligible for open repair, but can reduce aneurysm-related mortality.
Powell JT, Ulug P, Response to Kosmas Paraskevas, Lancet, ISSN: 0140-6736
Mason AJ, Gomes M, Grieve R, et al., 2017, Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial, Clinical Trials, Vol: 14, Pages: 357-367, ISSN: 1740-7745
Background/aims: The analyses of randomised controlled trials with missing data typically assume that, after conditioningon the observed data, the probability of missing data does not depend on the patient’s outcome, and so the data are ‘missingat random’ . This assumption is usually implausible, for example, because patients in relatively poor health may be more likelyto drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicitedexpert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrierto implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop anew practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data.Methods: We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategyversus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation,21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L).We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinionabout quality of life differences between patients with missing versus complete data. We show how this expert opinioncan define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing datato depend upon unobserved patient characteristics.Results: A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of lifescores were lower on average for the patients with missing versus complete data, but there was considerable uncertaintyin these
Drewe CJ, Parker LP, Kelsey LJ, et al., 2017, Haemodynamics and stresses in abdominal aortic aneurysms: A fluid-structure interaction study into the effect of proximal neck and iliac bifurcation angle, Journal of Biomechanics, Vol: 60, Pages: 150-156, ISSN: 0021-9290
Our knowledge of how geometry influences abdominal aortic aneurysm (AAA) biomechanics is still developing. Both iliac bifurcation angle and proximal neck angle could impact the haemodynamics and stresses within AAA. Recent comparisons of the morphology of ruptured and intact AAA show that cases with large iliac bifurcation angles are less likely to rupture than those with smaller angles. We aimed to perform fluid-structure interaction (FSI) simulations on a range of idealised AAA geometries to conclusively determine the influence of proximal neck and iliac bifurcation angle on AAA wall stress and haemodynamics.Peak wall shear stress (WSS) and time-averaged WSS (TAWSS) in the AAA sac region only increased when the proximal neck angle exceeded 30°. Both peak WSS (p < 0.0001) and peak von Mises wall stress (p = 0.027) increased with iliac bifurcation angle, whereas endothelial cell activation potential (ECAP) decreased with iliac bifurcation angle (p < 0.001) and increased with increasing neck angle.These observations may be important as AAAs have been shown to expand, develop thrombus and rupture in areas of low WSS. Here we show that AAAs with larger iliac bifurcation angles have higher WSS, potentially reducing the likelihood of rupture. Furthermore, ECAP was lower in AAA geometries with larger iliac bifurcation angles, implying less likelihood of thrombus development and wall degeneration. Therefore our findings could help explain the clinical observation of lower rupture rates associated with AAAs with large iliac bifurcation angles.
Sidloff DA, Saratzis A, Sweeting MJ, et al., 2017, Sex differences in mortality after abdominal aortic aneurysm repair in the UK., British Journal of Surgery, Vol: 104, Pages: 1656-1664, ISSN: 1365-2168
BACKGROUND: The UK abdominal aortic aneurysm (AAA) screening programmes currently invite only men for screening because the benefit in women is uncertain. Perioperative risk is critical in determining the effectiveness of screening, and contemporary estimates of these risks in women are lacking. The aim of this study was to compare mortality following AAA repair between women and men in the UK. METHODS: Anonymized data from the UK National Vascular Registry (NVR) for patients undergoing AAA repair (January 2010 to December 2014) were analysed. Co-variables were extracted for analysis by sex. The primary outcome measure was in-hospital mortality. Secondary outcome measures included mortality by 5-year age groups and duration of hospital stay. Logistic regression was performed to adjust for age, calendar time, AAA diameter and smoking status. NVR-based outcomes were checked against Hospital Episode Statistics (HES) data. RESULTS: A total of 23 245 patients were included (13·0 per cent women). Proportionally, more women than men underwent open repair. For elective open AAA repair, the in-hospital mortality rate was 6·9 per cent in women and 4·0 per cent in men (odds ratio (OR) 1·48, 95 per cent c.i. 1·08 to 2·02; P = 0·014), whereas for elective endovascular AAA repair it was 1·8 per cent in women and 0·7 per cent in men (OR 2·86, 1·72 to 4·74; P < 0·001); the results in HES were similar. For ruptured AAA, there was no sex difference in mortality within the NVR; however, in HES, for ruptured open AAA repair, the in-hospital mortality rate was higher in women (33·6 versus 27·1 per cent; OR 1·36, 1·16 to 1·59; P < 0·001). CONCLUSION: Women have a higher in-hospital mortality rate than men after elective AAA repair even after adjustment. This higher mortality may have an impact on the benefit offered by any screening programme offered
Powell JT, 2017, Mapping the workload associated with intact abdominal aortic aneurysm, European Journal of Vascular and Endovascular Surgery, Vol: 53, Pages: 765-765, ISSN: 1078-5884
Ulug P, Sweeting MJ, von Allmen RS, et al., 2017, 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, Vol: 389, Pages: 2482-2491, ISSN: 0140-6736
Background: Prognosis for women with abdominal aortic aneurysm might be worse than the prognosis for men. We aimed to systematically quantify the differences in outcomes between men and women being assessed for repair of intact abdominal aortic aneurysm using data from study periods after the year 2000.Methods: In these systematic reviews and meta-analysis, we identified studies (randomised, cohort, or cross-sectional) by searching MEDLINE, Embase, CENTRAL, and grey literature published between Jan 1, 2005, and Sept 2, 2016, for two systematic reviews and Jan 1, 2009, and Sept 2, 2016, for one systematic review. Studies were included if they were of both men and women, with data presented for each sex separately, with abdominal aortic aneurysms being assessed for aneurysm repair by either endovascular repair (EVAR) or open repair. We conducted three reviews based on whether studies reported the proportion morphologically suitable (within manufacturers' instructions for use) for EVAR (EVAR suitability review), non-intervention rates (non-intervention review), and 30-day mortality (operative mortality review) after intact aneurysm repair. Studies had to include at least 20 women (for the EVAR suitability review), 20 women (for the non-intervention review), and 50 women (for the operative mortality review). Studies were excluded if they were review articles, editorials, letters, or case reports. For the operative review, studies were also excluded if they only provided hazard ratios or only reported in-hospital mortality. We assessed the quality of the studies using the Newcastle–Ottawa scoring system, and contacted authors for the provision of additional data if needed. We combined results across studies by random-effects meta-analysis. This study is registered with PROSPERO, number CRD42016043227.Findings: Five studies assessed the morphological eligibility for EVAR (1507 men, 400 women). The overall pooled proportion of women eligible (34%) for EVAR was lower
Powell JT, 2017, Abdominal Aortic Aneurysm Repair in England and the United States, New England Journal of Medicine, Vol: 376, Pages: 998-998, ISSN: 0028-4793
Ulug P, Sweeting MJ, von Allmen RS, et al., Women assessed for intact abdominal aortic aneurysm repair fare worse than men: systematic reviews of morphological suitability for endovascular repair, non-intervention rates and operative mortality, Lancet, ISSN: 1474-547X
Objective: To systematically quantify the differences in outcomes between men and women being assessed for repair of intact abdominal aortic aneurysm (AAA) in contemporary data (2000 or later). Methods: Three systematic reviews were undertaken, according to PRISMA guidelines of studies reporting separately for men and women the proportion morphologically suitable (within Manufacturers’ Instructions for Use) for endovascular repair (EVAR), non-intervention rates, and 30-day mortality after intact aneurysm repair. The minimum numbers for studies in each review were based on inclusion of 20, 20 and 50 women, respectively. Studies (randomised, cohort or cross-sectional) were identified by searching MEDLINE, Embase, CENTRAL and other sources until 2nd September 2016 and quality assessed using the Newcastle–Ottawa scoring system. Results were combined across studies by random-effects meta-analysis. The reviews are registered in PROSPERO: CRD42016043227. Results: Five studies evaluated the morphological eligibility for EVAR (1507 men, 400 women). The overall proportion of women eligible for EVAR was much lower than in men, 34% versus 54%, odds ratio 0.44 [95%CI 0.32,0.62]. Four single centre studies reported non-intervention rates (1365 men, 247 women). The overall non-intervention rates were higher in women than men, 34% versus 19%, odds ratio 2.27 [95%CI 1.21,4.23]. The review of 30-day mortality included nine studies (52018 men, 10076 women). The overall estimate for EVAR was higher in women than men: 2.3% versus 1.4%, odds ratio 1.67 [95%CI 1.38,2.04]. The overall estimate for open repair also was higher in women: 5.4% versus 2.8% in men, odds ratio 1.76 [95%CI 1.35,2.30]. Interpretation: A smaller proportion of women are eligible for EVAR, a higher proportion of women are not offered intervention, and operative mortality was much higher in women for both EVAR and open repair. The management of AAA in women needs improvement.
Powell JT, Sweeting MJ, Ulug P, et al., 2017, Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years, British Journal of Surgery, Vol: 104, Pages: 166-178, ISSN: 1365-2168
BackgroundThe erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation.MethodsAn individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention.ResultsThe analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0–6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization.ConclusionThe early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1
von Allmen RS, Gahl B, Powell JT, 2016, Editor's choice - Incidence of stroke following thoracic endovascular aortic repair for descending aortic aneurysm: a systematic review of the literature with meta-analysis., European Journal of Vascular and Endovascular Surgery, Vol: 53, Pages: 176-184, ISSN: 1532-2165
OBJECTIVE: Stroke is an increasingly recognised complication following thoracic endovascular aortic repair (TEVAR). The aim of this study was to systematically synthesise the published data on perioperative stroke incidence during TEVAR for patients with descending thoracic aneurysmal disease and to assess the impact of left subclavian artery (LSA) coverage on stroke incidence. METHODS: A systematic review of English and German articles on perioperative (in-hospital or 30 day) stroke incidence following TEVAR for descending aortic aneurysm was performed, including studies with ≥50 cases, using MEDLINE and EMBASE (2005-2015). The pooled prevalence of perioperative stroke with 95% CI was estimated using random effect analysis. Heterogeneity was examined using I(2) statistic. RESULTS: Of 215 studies identified, 10 were considered suitable for inclusion. The included studies enrolled a total of 2594 persons (61% male) between 1997 and 2014 with a mean weighted age of 71.8 (95% CI 71.1-73.6) years. The pooled prevalence for stroke was 4.1% (95% CI 2.9-5.5) with moderate heterogeneity between studies (I(2) = 49.8%, p = .04). Five studies reported stroke incidences stratified by the management of the LSA, that is uncovered versus covered and revascularised versus covered and not-revascularised. In cases where the LSA remained uncovered, the pooled stroke incidence was 3.2% (95% CI 1.0-6.5). There was, however, an indication that stroke incidence increased following LSA coverage, to 5.3% (95% CI 2.6-8.6) in those with a revascularisation and 8.0% (95% CI 4.1-12.9) in those without revascularisation. CONCLUSION: Stroke incidence is an important morbidity after TEVAR, and probably increases if the LSA is covered during the procedure, particularly in those without revascularisation.
Powell JT, 2016, Commentary on: "The DanCavas pilot study of multifaceted screening for subclinical cardiovascular disease in men and women aged 65-74 years", European Journal of Vascular and Endovascular Surgery, Vol: 53, Pages: 132-132, ISSN: 1532-2165
Powell JT, 2016, Prophylactic abdominal aortic aneurysm repair? Open repair brings early pain but later gain., European Journal of Vascular and Endovascular Surgery, Vol: 52, Pages: 719-720, ISSN: 1532-2165
Jones GT, Tromp G, Kuivaniemi H, et al., 2016, Meta-analysis of genome-wide association studies for abdominal aortic aneurysm identifies four new disease-specific risk loci., Circulation Research, Vol: 120, Pages: 341-353, ISSN: 1524-4571
RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS). METHODS AND RESULTS: Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
Powell JT, 2016, Diverse requirements for efficient population screening for abdominal aortic aneurysm, Circulation, Vol: 134, Pages: 1149-1151, ISSN: 0009-7322
Patel R, Sweeting MJ, Powell JT, et al., 2016, Endovascular versus open repair of abdominal aortic aneurysm in 15-years' follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a randomised controlled trial, Lancet, Vol: 388, Pages: 2366-2374, ISSN: 1474-547X
BackgroundShort-term survival benefits of endovascular aneurysm repair (EVAR) versus open repair of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival benefit is lost after a few years. We investigated whether EVAR had a long-term survival benefit compared with open repair.MethodsWe used data from the EVAR randomised controlled trial (EVAR trial 1), which enrolled 1252 patients from 37 centres in the UK between Sept 1, 1999, and Aug 31, 2004. Patients had to be aged 60 years or older, have aneurysms of at least 5·5 cm in diameter, and deemed suitable and fit for either EVAR or open repair. Eligible patients were randomly assigned (1:1) using computer-generated sequences of randomly permuted blocks stratified by centre to receive either EVAR (n=626) or open repair (n=626). Patients and treating clinicians were aware of group assignments, no masking was used. The primary analysis compared total and aneurysm-related deaths in groups until mid-2015 in the intention-to-treat population. This trial is registered at ISRCTN (ISRCTN55703451).FindingsWe recruited 1252 patients between Sept 1, 1999, and Aug 31, 2004. 25 patients (four for mortality outcome) were lost to follow-up by June 30, 2015. Over a mean of 12·7 years (SD 1·5; maximum 15·8 years) of follow-up, we recorded 9·3 deaths per 100 person-years in the EVAR group and 8·9 deaths per 100 person-years in the open-repair group (adjusted hazard ratio [HR] 1·11, 95% CI 0·97–1·27, p=0·14). At 0–6 months after randomisation, patients in the EVAR group had a lower mortality (adjusted HR 0·61, 95% CI 0·37–1·02 for total mortality; and 0·47, 0·23–0·93 for aneurysm-related mortality, p=0·031), but beyond 8 years of follow-up open-repair had a significantly lower mortality (adjusted HR 1·25, 95% CI 1·00–1·56, p=0&mi
Kelsey LJ, Miller K, Norman PE, et al., 2016, The influence of downstream branching arteries on upstream haemodynamics, JOURNAL OF BIOMECHANICS, Vol: 49, Pages: 3090-3096, ISSN: 0021-9290
Kiru G, Bicknell C, Falaschetti E, et al., 2016, 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), Health Technology Assessment, Vol: 20, ISSN: 1366-5278
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.
Kelsey LJ, Powell JT, Norman PE, et al., 2016, A comparison of hemodynamic metrics and intraluminal thrombus burden in a common iliac artery aneurysm, International Journal for Numerical Methods in Biomedical Engineering, Vol: 33, ISSN: 2040-7947
Aneurysms of the common iliac artery (CIAA) are typically found in association with an abdominal aortic aneurysm (AAA). Isolated CIAAs, in the absence of an AAA, are uncommon. Similar to AAAs, CIAA may develop intraluminal thrombus (ILT). As isolated CIAAs have a contralateral common iliac artery for comparison, they provide an opportunity to study the hemodynamic mechanisms behind ILT formation. In this study, we compared a large isolated CIAA and the contralateral iliac artery using computational fluid dynamics to determine if hemodynamic metrics correlate with the location of ILT. We performed a comprehensive computational fluid dynamics study and investigated the residence time of platelets and monocytes, velocity fields, time-averaged wall shear stress, oscillatory shear index, and endothelial cell activation potential. We then correlated these data to ILT burden determined with computed tomography. We found that high cell residence times, low time-averaged wall shear stress, high oscillatory shear index, and high endothelial cell activation potential all correlate with regions of ILT development. Our results show agreement with previous hypotheses of thrombus formation in AAA and provide insights into the computational hemodynamics of iliac artery aneurysms.
van 't Hof FNG, Ruigrok YM, Lee CH, et al., 2016, Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms., Journal of the American Heart Association, Vol: 5, ISSN: 2047-9980
BACKGROUND: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. METHODS AND RESULTS: We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10(-3)). CONCLUSIONS: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.
Bicknell CD, Kiru G, Falaschetti E, et al., 2016, 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), European Heart Journal, Vol: 37, Pages: 3213-3221, ISSN: 1522-9645
Aims The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial investigated whether ACE-inhibition reduces small abdominal aortic aneurysms (AAA) growth rate, independent of blood pressure (BP) lowering.Methods and results A three-arm, multi-centre, single-blind, and randomized controlled trial (ISRCTN51383267) was conducted in 14 hospitals in England. Subjects aged ≥55 years with AAA diameter 3.0–5.4 cm were randomized 1:1:1 to receive perindopril arginine 10 mg, or amlodipine 5 mg, or placebo and followed 3–6 monthly over 2 years. The primary outcome was aneurysm growth rate (based on external antero-posterior ultrasound measurements in the longitudinal plane), determined by multi-level modelling to provide maximum likelihood estimates. Two hundred and twenty-four subjects were randomized (2011–2013) to placebo (n = 79), perindopril (n = 73), or amlodipine (n = 72). Mean (SD) changes in mid-trial systolic BP (12 months) were 0.5 (14.3) mmHg, P = 0.78 compared with baseline, −9.5 (13.1) mmHg (P < 0.001), and −6.7 (12.0) mmHg (P < 0.001), respectively. No significant differences in the modelled annual growth rates were apparent [1.68 mm (SE 0.2), 1.77 mm (0.2), and 1.81 mm (0.2), respectively]. The estimated difference in annual growth between the perindopril and placebo groups was 0.08 mm (CI −0.50, 0.65). Similar numbers of AAAs in each group reached 5.5 cm diameter and/or underwent elective surgery: 11 receiving placebo, 10 perindopril, and 11 amlodipine.Conclusion Small AAA growth rates were lower than anticipated, but there was no significant impact of perindopril compared with placebo or placebo and amlodipine, combined despite more effective BP lowering.
Ulug P, Powell J, Sweeting MJ, et al., 2016, Meta-analysis of the current prevalence of screen-detected abdominal aortic aneurysm in women, British Journal of Surgery, Vol: 103, Pages: 1097-1104, ISSN: 1365-2168
BackgroundAlthough women represent an increasing proportion of those presenting with abdominal aortic aneurysm (AAA) rupture, the current prevalence of AAA in women is unknown. The contemporary population prevalence of screen-detected AAA in women was investigated by both age and smoking status.MethodsA systematic review was undertaken of studies screening for AAA, including over 1000 women, aged at least 60 years, done since the year 2000. Studies were identified by searching MEDLINE, Embase and CENTRAL databases until 13 January 2016. Study quality was assessed using the Newcastle–Ottawa scoring system.ResultsEight studies were identified, including only three based on population registers. The largest studies were based on self-purchase of screening. Altogether 1 537 633 women were screened. Overall AAA prevalence rates were very heterogeneous, ranging from 0·37 to 1·53 per cent: pooled prevalence 0·74 (95 per cent c.i. 0·53 to 1·03) per cent. The pooled prevalence increased with both age (more than 1 per cent for women aged over 70 years) and smoking (more than 1 per cent for ever smokers and over 2 per cent in current smokers).ConclusionThe current population prevalence of screen-detected AAA in older women is subject to wide demographic variation. However, in ever smokers and those over 70 years of age, the prevalence is over 1 per cent.
Powell JT, Sweeting MJ, 2015, Retrospective Studies, EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, Vol: 50, Pages: 675-678, ISSN: 1078-5884
Powell JT, Hinchliffe RJ, 2015, Emerging strategies to treat ruptured abdominal aortic aneurysms, Expert Review of Cardiovascular Therapy, Vol: 13, Pages: 1411-1418, ISSN: 1477-9072
Population screening programmes and a falling population prevalence of smoking have led to a declining incidence of ruptured abdominal aortic aneurysms in men. However, ruptured abdominal aortic aneurysms remain a common vascular surgical emergency, with an increasing proportion of ruptures being in women. About one quarter of the ruptures have a juxta-renal aneurysm and are more challenging to repair using endovascular technologies. Endovascular technologies may not reduce the overall mortality, compared with open surgical repair, but appear to offer early benefits with respect to patient quality of life at acceptable cost. Challenges over the next 5 years include widening the access to repair, developing an accurate bedside risk scoring tool, as well as optimising strategies for pre-operative resuscitation, standardising peri-operative care and the management of post-operative complications.
Powell JT, Ulug P, 2015, PATIENTS AND TRIAL ENROLMENT DECISIONS Flexibility in trial enrolment decisions, BMJ, Vol: 351, ISSN: 1756-1833
Powell JT, 2015, Questionnaires for Surgical Research: Not Always a Simple Option, European Journal of Vascular and Endovascular Surgery, Vol: 50, Pages: 534-534, ISSN: 1532-2165
Sweeting MJ, Balm R, Desgranges P, et al., 2015, Individual-patient meta-analysis of three randomized trials comparing endovascular versus open repair for ruptured abdominal aortic aneurysm, British Journal of Surgery, Vol: 102, Pages: 1229-1239, ISSN: 1365-2168
BACKGROUND: The benefits of endovascular repair of ruptured abdominal aortic aneurysm remain controversial, without any strong evidence about advantages in specific subgroups. METHODS: An individual-patient data meta-analysis of three recent randomized trials of endovascular versus open repair of abdominal aortic aneurysm was conducted according to a prespecified analysis plan, reporting on results to 90 days after the index event. RESULTS: The trials included a total of 836 patients. The mortality rate across the three trials was 31·3 per cent for patients randomized to endovascular repair/strategy and 34·0 per cent for those randomized to open repair at 30 days (pooled odds ratio 0·88, 95 per cent c.i. 0·66 to 1·18), and 34·3 and 38·0 per cent respectively at 90 days (pooled odds ratio 0·85, 0·64 to 1·13). There was no evidence of significant heterogeneity in the odds ratios between trials. Mean(s.d.) aneurysm diameter was 8·2(1·9) cm and the overall in-hospital mortality rate was 34·8 per cent. There was no significant effect modification with age or Hardman index, but there was indication of an early benefit from an endovascular strategy for women. Discharge from the primary hospital was faster after endovascular repair (hazard ratio 1·24, 95 per cent c.i. 1·04 to 1·47). For open repair, 30-day mortality diminished with increasing aneurysm neck length (adjusted odds ratio 0·69 (95 per cent c.i. 0·53 to 0·89) per 15 mm), but aortic diameter was not associated with mortality for either type of repair. CONCLUSION: Survival to 90 days following an endovascular or open repair strategy is similar for all patients and for the restricted population anatomically suitable for endovascular repair. Women may benefit more from an endovascular strategy than men and patients are, on average, discharged sooner after endovascular repair.
Sweeting MJ, Ulug P, Powell JT, et al., 2015, Ruptured aneurysm trials: The importance of longer-term outcomes and meta-analysis for 1-year mortality., European Journal of Vascular and Endovascular Surgery, Vol: 50, Pages: 297-302, ISSN: 1532-2165
OBJECTIVE: To assess current knowledge for the management of ruptured abdominal aortic aneurysm (AAA), based on the 1-year outcomes of 3 recent randomised trials. METHODS: An individual patient data meta-analysis of three recent randomised trials of endovascular versus open repair, including 817 patients, was conducted according to a pre-specified analysis plan, report all-cause mortality and re-interventions at 1 year after the index event. RESULTS: Mortality across the 3 trials at 1-year was 38.6% for the EVAR or endovascular strategy patient groups and 42.8% for the open repair groups, pooled odds ratio 0.84 (95% CI 0.63-1.11), p = .209. There was no evidence of heterogeneity in the odds ratios between trials. When the patients in the endovascular strategy group of the IMPROVE trial were restricted to those with proven rupture who were anatomically suitable for endovascular repair, the pooled odds ratio reduced slightly to 0.80 (95% CI 0.56-1.16), p = .240. CONCLUSIONS: After 1 year there is a consistent but non-significant trend for lower mortality for EVAR or an endovascular strategy. Taken together with the recent gains in health economic outcomes demonstrated at 1 year in the IMPROVE trial, the evidence suggests that endovascular repair should be used more widely for ruptured aneurysms.
Bicknell C, Powell JT, 2015, Aortic disease: thoracic endovascular aortic repair, HEART, Vol: 101, Pages: 586-591, ISSN: 1355-6037
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