Summary Background Short-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. Methods We 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). Findings We 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=0·048 for total mortality; and 5·82, 1·64–20·65, p=0·0064 for aneurysm-related mortality). The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture (13 deaths 7% in EVAR vs two 1% in open repair), with increased cancer mortality also observed in the EVAR group. Interpretation EVAR has an early survival benefit but an inferior late survival compared with open repair, which needs to be addressed by lifelong surveillance of EVAR and re-intervention if necessary. Funding UK National Institute for Health Research, Camelia Botnar Arterial Research Foundation.
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.
Summary 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 than it was in men (54%; odds ratio OR 0·44, 95% CI 0·32–0·62). Four single-centre studies reported non-intervention rates (1365 men, 247 women). The overall pooled non-intervention rates were higher in women (34%) than men (19%; OR 2·27, 95% CI 1·21–4·23). The review of 30-day mortality included nine studies (52 018 men, 11 076 women). The overall pooled estimate for EVAR was higher in women (2·3%) than in men (1·4%; OR 1·67, 95% CI 1·38–2·04). The overall estimate for open repair also was higher in women (5·4%) than in men (2·8%; OR 1·76, 95% CI 1·35–2·30). Interpretation Compared with men, a smaller proportion of women are eligible for EVAR, a higher proportion of women are not offered intervention, and operative mortality is much higher in women for both EVAR and open repair. The management of abdominal aortic aneurysm in women needs improvement. Funding National Institute for Health Research (UK).
Objectives: To compare the performance of different meta‐analysis methods for pooling odds ratios when applied to sparse event data with emphasis on the use of continuity corrections.
Background: ...Meta‐analysis of side effects from RCTs or risk factors for rare diseases in epidemiological studies frequently requires the synthesis of data with sparse event rates. Combining such data can be problematic when zero events exist in one or both arms of a study as continuity corrections are often needed, but, these can influence results and conclusions.
Methods: A simulation study was undertaken comparing several meta‐analysis methods for combining odds ratios (using various classical and Bayesian methods of estimation) on sparse event data. Where required, the routine use of a constant and two alternative continuity corrections; one based on a function of the reciprocal of the opposite group arm size; and the other an empirical estimate of the pooled effect size from the remaining studies in the meta‐analysis, were also compared. A number of meta‐analysis scenarios were simulated and replicated 1000 times, varying the ratio of the study arm sizes.
Results: Mantel–Haenszel summary estimates using the alternative continuity correction factors gave the least biased results for all group size imbalances. Logistic regression was virtually unbiased for all scenarios and gave good coverage properties. The Peto method provided unbiased results for balanced treatment groups but bias increased with the ratio of the study arm sizes. The Bayesian fixed effect model provided good coverage for all group size imbalances. The two alternative continuity corrections outperformed the constant correction factor in nearly all situations. The inverse variance method performed consistently badly, irrespective of the continuity correction used.
Conclusions: Many routinely used summary methods provide widely ranging estimates when applied to sparse data with high imbalance between the size of the studies' arms. A sensitivity analysis using several methods and continuity correction factors is advocated for routine practice. Copyright 2004 John Wiley & Sons, Ltd.
Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated ...comprehensively, because available studies have involved limited genomic scope and limited sample sizes.
This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention.
Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1.7 million genetic variants. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22,242 CAD cases and 460,387 noncases from the UK Biobank.
The hazard ratio (HR) for CAD was 1.71 (95% confidence interval CI: 1.68 to 1.73) per SD increase in metaGRS, an association larger than any other externally tested genetic risk score previously published. The metaGRS stratified individuals into significantly different life course trajectories of CAD risk, with those in the top 20% of metaGRS distribution having an HR of 4.17 (95% CI: 3.97 to 4.38) compared with those in the bottom 20%. The corresponding HR was 2.83 (95% CI: 2.61 to 3.07) among individuals on lipid-lowering or antihypertensive medications. The metaGRS had a higher C-index (C = 0.623; 95% CI: 0.615 to 0.631) for incident CAD than any of 6 conventional factors (smoking, diabetes, hypertension, body mass index, self-reported high cholesterol, and family history). For men in the top 20% of metaGRS with >2 conventional factors, 10% cumulative risk of CAD was reached by 48 years of age.
The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screening in early life to complement conventional risk prediction.
The Clinical Practice Research Datalink (CPRD) is a widely used data resource, representative in demographic profile, with accurate death recordings but it is unclear if mortality rates within CPRD ...GOLD are similar to rates in the general population. Rates may additionally be affected by selection bias caused by the requirement that a cohort have a minimum lookback window, i.e. observation time prior to start of at-risk follow-up. Standardised Mortality Ratios (SMRs) were calculated incorporating published population reference rates from the Office for National Statistics (ONS), using Poisson regression with rates in CPRD GOLD contrasted to ONS rates, stratified by age, calendar year and sex. An overall SMR was estimated along with SMRs presented for cohorts with different lookback windows (1, 2, 5, 10 years). SMRs were stratified by calendar year, length of follow-up and age group. Mortality rates in a random sample of 1 million CPRD GOLD patients were slightly lower than the national population SMR = 0.980 95% confidence interval (CI) (0.973, 0.987). Cohorts with observational lookback had SMRs below one 1 year of lookback; SMR = 0.905 (0.898, 0.912), 2 years; SMR = 0.881 (0.874, 0.888), 5 years; SMR = 0.849 (0.841, 0.857), 10 years; SMR = 0.837 (0.827, 0.847). Mortality rates in the first two years after patient entry into CPRD were higher than the general population, while SMRs dropped below one thereafter. Mortality rates in CPRD, using simple entry requirements, are similar to rates seen in the English population. The requirement of at least a single year of lookback results in lower mortality rates compared to national estimates.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Population screening for abdominal aortic aneurysm (AAA) has commenced in several countries, and has been shown to reduce AAA-related mortality by up to 50%. Most men who screen positive ...have an AAA <5.5 cm in diameter, the referral threshold for treatment, and are entered into an ultrasound surveillance program. This study aimed to determine the risk of ruptured AAA (rAAA) in men under surveillance.
METHODS:Men in the National Health Service AAA Screening Programme who initially had a small (3–4.4 cm) or medium (4.5–5.4 cm) AAA were followed up. The screening program’s database collected data on ultrasound AAA diameter measurements, dates of referral, and loss to follow-up. Local screening programs recorded adverse outcomes, including rAAA and death. Rupture and mortality rates were calculated by initial and final known AAA diameter.
RESULTS:A total of 18 652 men were included (50 103 person-years of surveillance). Thirty-one men had rAAA during surveillance, of whom 29 died. Some 952 men died of other causes during surveillance, mainly cardiovascular complications (26.3%) and cancer (31.2%). The overall mortality rate was 1.96% per annum, similar for men with small and medium AAAs. The rAAA risk was 0.03% per annum (95% CI, 0.02%–0.05%) for men with small AAAs and 0.28% (0.17%–0.44%) for medium AAAs. The rAAA risk for men with AAAs just below the referral threshold (5.0–5.4 cm) was 0.40% (0.22%–0.73%).
CONCLUSIONS:The risk of rAAA under surveillance is <0.5% per annum, even just below the present referral threshold of 5.5 cm, and only 0.4% of men under surveillance are estimated to rupture before referral. It can be concluded that men with small and medium screen-detected AAAs are safe provided they are enrolled in an intensive surveillance program, and that there is no evidence that the current referral threshold of 5.5 cm should be changed.
Short-term survival benefits of endovascular aneurysm repair (EVAR) compared with open repair (OR) of intact abdominal aortic aneurysms have been shown in randomised trials, but this early survival ...benefit is soon lost. Survival benefit of EVAR was unclear at follow-up to 10 years.
To assess the long-term efficacy of EVAR against OR in patients deemed fit and suitable for both procedures (EVAR trial 1; EVAR-1); and against no intervention in patients unfit for OR (EVAR trial 2; EVAR-2). To appraise the long-term significance of type II endoleak and define criteria for intervention.
Two national, multicentre randomised controlled trials: EVAR-1 and EVAR-2.
Patients were recruited from 37 hospitals in the UK between 1 September 1999 and 31 August 2004.
Men and women aged ≥ 60 years with an aneurysm of ≥ 5.5 cm (as identified by computed tomography scanning), anatomically suitable and fit for OR were randomly assigned 1 : 1 to either EVAR (
= 626) or OR (
= 626) in EVAR-1 using computer-generated sequences at the trial hub. Patients considered unfit were randomly assigned to EVAR (
= 197) or no intervention (
= 207) in EVAR-2. There was no blinding.
EVAR, OR or no intervention.
The primary end points were total and aneurysm-related mortality until mid-2015 for both trials. Secondary outcomes for EVAR-1 were reinterventions, costs and cost-effectiveness.
In EVAR-1, over a mean of 12.7 years (standard deviation 1.5 years; maximum 15.8 years), we recorded 9.3 deaths per 100 person-years in the EVAR group and 8.9 deaths per 100 person-years in the OR group adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.97 to 1.27;
= 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 to 1.02 for total mortality; HR 0.47, 95% CI 0.23 to 0.93 for aneurysm-related mortality;
= 0.031), but beyond 8 years of follow-up patients in the OR group had a significantly lower mortality (adjusted HR 1.25, 95% CI 1.00 to 1.56,
= 0.048 for total mortality; HR 5.82, 95% CI 1.64 to 20.65,
= 0.0064 for aneurysm-related mortality). The increased aneurysm-related mortality in the EVAR group after 8 years was mainly attributable to secondary aneurysm sac rupture, with increased cancer mortality also observed in the EVAR group. Overall, aneurysm reintervention rates were higher in the EVAR group than in the OR group, 4.1 and 1.7 per 100 person-years, respectively (
< 0.001), with reinterventions occurring throughout follow-up. The mean difference in costs over 14 years was £3798 (95% CI £2338 to £5258). Economic modelling based on the outcomes of the EVAR-1 trial showed that the cost per quality-adjusted life-year gained over the patient's lifetime exceeds conventional thresholds used in the UK. In EVAR-2, patients died at the same rate in both groups, but there was suggestion of lower aneurysm mortality in those who actually underwent EVAR. Type II endoleak itself is not associated with a higher rate of mortality.
Devices used were implanted between 1999 and 2004. Newer devices might have better results. Later follow-up imaging declined, particularly for OR patients. Methodology to capture reinterventions changed mainly to record linkage through the Hospital Episode Statistics administrative data set from 2009.
EVAR has an early survival benefit but an inferior late survival benefit compared with OR, which needs to be addressed by lifelong surveillance of EVAR and reintervention if necessary. EVAR does not prolong life in patients unfit for OR. Type II endoleak alone is relatively benign.
To find easier ways to monitor sac expansion to trigger timely reintervention.
Current Controlled Trials ISRCTN55703451.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the results will be published in full in
; Vol. 22, No. 5. See the NIHR Journals Library website for further project information.
Background The National Health Service (NHS) abdominal aortic aneurysm (AAA) screening programme (NAAASP) in England screens 65-year-old men. The programme monitors those with an aneurysm, and early ...intervention for large aneurysms reduces ruptures and AAA-related mortality. AAA screening services have been disrupted following COVID-19 but it is not known how this may impact AAA-related mortality, or where efforts should be focussed as services resume. Methods We repurposed a previously validated discrete event simulation model to investigate the impact of COVID-19-related service disruption on key outcomes. This model was used to explore the impact of delayed invitation and reduced attendance in men invited to screening. Additionally, we investigated the impact of temporarily suspending scans, increasing the threshold for elective surgery to 7cm and increasing drop-out in the AAA cohort under surveillance, using data from NAAASP to inform the population. Findings Delaying invitation to primary screening up to two years had little impact on key outcomes whereas a 10% reduction in attendance could lead to a 2% lifetime increase in AAA-related deaths. In surveillance patients, a 1-year suspension of surveillance or increase in the elective threshold resulted in a 0.4% increase in excess AAA-related deaths (8% in those 5-5.4cm at the start). Longer suspensions or a doubling of drop-out from surveillance would have a pronounced impact on outcomes. Interpretation Efforts should be directed towards encouraging men to attend AAA screening service appointments post-COVID-19. Those with AAAs on surveillance should be prioritised as the screening programme resumes, as changes to these services beyond one year are likely to have a larger impact on surgical burden and AAA-related mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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