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.

BACKGROUND: The 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. METHODS: An 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. RESULTS: The 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. CONCLUSION: The 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, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.

Multicentre study of abdominal aortic aneurysm measurement and enlargement.

BACKGROUND: No effective treatment is currently available to prevent progression of small and medium-sized abdominal aortic aneurysms (AAAs). Identification of drugs with sufficient promise to justify large expensive randomized trials remains challenging. One potentially useful strategy is to look for associations between commonly used drugs and AAA enlargement in appropriately adjusted observational studies. METHODS: Potential AAA measurements were identified from abdominal imaging reports in the electronic data files of three medical centres from 1995 to 2010. AAA measurements were extracted manually and patients with an aneurysm of 3 cm or larger, who had at least two measurements over an interval of at least 6 months, were identified. Other data were obtained from the electronic data files (demographics, co-morbidities, smoking status, drug use) to conduct a propensity analysis of the associations of drugs and other factors with AAA enlargement. RESULTS: From 52,962 abdominal imaging studies, 5362 patients with an AAA of 3 cm or more were identified, of whom 2428 had at least two measurements over at least 6 months. Mean AAA follow-up was 3.4 years and the mean AAA enlargement rate was 2.0 mm per year. Propensity analysis demonstrated no significant association of AAA enlargement with statins, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Diabetes was associated with a reduction in AAA enlargement of 1.2 mm per year (P = 0.008), and chronic obstructive pulmonary disease was associated with increased enlargement (0.5 mm per year; P = 0.050). Moderate AAA measurement variation and substantial terminal digit preference were also observed, but the digit preference became less pronounced after 2000. CONCLUSION: This study confirms the negative association of diabetes with AAA progression. There was no evidence that commonly used cardiovascular drugs affect AAA enlargement.

Cost-effectiveness at two years in the VA Open Versus Endovascular Repair Trial.

BACKGROUND: Long-term clinical outcomes have been similar for endovascular and open repair of abdominal aortic aneurysm (AAA), increasing the importance of comparing cost-effectiveness. METHODS: We compared data to two years from a multicenter randomized trial of 881 patients. Quality-adjusted life years (QALYs) were calculated from EQ-5D questionnaires. Healthcare utilization data were obtained from patients and from national VA and Medicare sources. VA costs were obtained using methods previously developed by the VA Health Economics Resource Center. Costs for non-VA care were determined from Medicare or billing data. RESULTS: Mean life-years were 1.78 in the endovascular and 1.74 in the open repair group (P = 0.29), and mean QALYs were 1.462 in the endovascular and 1.461 in the open group (P = 0.78). Although graft costs were higher in the endovascular group ($14,052 vs. $1363; P < 0.001), length of stay was shorter (5.0 vs. 10.5 days; P < 0.001), resulting in lower cost of AAA repair hospitalization in the endovascular group ($37,068 vs. $42,970; P = 0.04). Costs remained lower after 2 years in the endovascular group but the difference was no longer significant (-$5019; 95% CI: -$16,720 to $4928; P = 0.35). The probability that endovascular repair was both more effective and less costly was 70.9% for life-years and 51.4% for QALYs. INTERPRETATION: Endovascular repair is a cost-effective alternative to open repair in the US VA healthcare system for at least the first two years.

The strange relationship between diabetes and abdominal aortic aneurysm.

In a 1997 report of a large abdominal aortic aneurysm (AAA) screening study, we observed a negative association between diabetes and AAA. Although this was not previously described and negative associations between diseases are rare, the credibility of the finding was supported by consistent results in several previous studies and by the absence of an obvious artifactual explanation. Since that time, a variety of studies of AAA diagnosis, both by screening and prospective clinical follow-up, have confirmed the finding. Other studies have reported slower aneurysm enlargement and fewer repairs for rupture in diabetics. The seeming protective effect of diabetes for AAA contrasts with its causal role in occlusive vascular disease and so provides a strong challenge to the traditional view of AAA as a manifestation of atherosclerosis. Research focused on a protective effect of diabetes has already increased our understanding of the etiology of AAA, and might eventually pave the way for new therapies to slow AAA progression.

Should abdominal aortic aneurysm be managed differently in women?

Although abdominal aortic aneurysm (AAA) is 4 to 6 times more common in men than in women, more than a third of all AAA deaths occur in women. In several reports from the UK Small Aneurysm Trial group, the rupture rate for women was 3-4 times that seen in men. A joint council of several vascular societies responded to these observations with the recommendation that AAA should be repaired earlier in women, at 4.5 cm to 5.0 cm rather than the 5.5 cm established in randomized trials for men. However, this recommendation does not appear to reflect a full consideration of the evidence. For example, population-based studies have reported mortality following AAA repair to be 40-60% higher in women than in men. Also, in the UK Small Aneurysm Trial itself, there was no trend toward a benefit from early repair in women. The totality of evidence available at present provides no good reason to alter for women the 5.5 cm threshold for elective repair established for men by the small AAA trials.

Screening for AAA in the USA.

The United States (U.S.) was home to both the first and the largest reported abdominal aortic aneurysm (AAA) screening programs to date. Influenced by the results of four randomized trials conducted outside the U.S., the U.S. Preventive Services Task Force (USPSTF) recommended one-time AAA screening with ultrasound for men 65-75 years old who have ever smoked. After the USPSTF report, the U.S. Congress added a Medicare benefit for free, one-time AAA screening with ultrasound for men who have smoked and for men and women with a family history of AAA. Screening may be underutilized in this target population, but recommendations by American vascular societies for much broader use of screening and repair than can be justified by the available evidence are influencing practice and threaten the effectiveness and cost-effectiveness of AAA screening in the U.S.

Risk factors for severe delayed postpolypectomy bleeding.

BACKGROUND AND STUDY AIMS: Postpolypectomy bleeding is a rare but serious adverse event. The aim of this study was to identify factors associated with the risk of severe delayed postpolypectomy bleeding. PATIENTS AND METHODS: This was a case-control study, comparing cases who developed hematochezia and required medical evaluation 6 hours to 14 days after colonoscopic polypectomy, and control patients who underwent polypectomy without delayed bleeding, and who were selected in approximately a 3 : 1 ratio. The following risk factors were specified a priori: resuming anticoagulation (within 1 week following polypectomy), aspirin use, hypertension, and polyp diameter. RESULTS: Of the 4592 patients who underwent colonoscopy with polypectomy, 41 patients (0.9 %) developed delayed postpolypectomy bleeding (cases), and 132 patients were selected as controls. The mean age was 64.3 years for cases and 65.4 years for controls. Cases presented on average 6 days after polypectomy (range 1 - 14 days), and 48 % required blood transfusion (average 4.2 units, range 0 - 17). Two patients required surgery. Anticoagulation was resumed following polypectomy in 34 % of cases compared with 9 % of controls (OR 5.2; 95 % CI 2.2 - 12.5; P < 0.001). For every 1 mm increase in polyp diameter, the risk of hemorrhage increased by 9 % (OR 1.09; 95 % CI 1.0 - 1.2; P = 0.008). Hypertension (OR 1.1) and aspirin use (OR 1.1) did not increase the risk of postpolypectomy bleeding. In exploratory analysis, diabetes (OR 2.5) and coronary artery disease (OR 3.0) were associated with postpolypectomy hemorrhage, but the association was no longer statistically significant once adjusted for the use of anticoagulation. CONCLUSIONS: Resuming anticoagulation following polypectomy and polyp diameter were strongly associated with increased risk of severe delayed postpolypectomy bleeding.

Abdominal aortic aneurysm in women.

OBJECTIVE: The purpose of this study was to compare abdominal aortic aneurysm (AAA) associations in men and women. METHODS: Veterans aged 50 to 79 years without a previous history of AAA underwent ultrasound screening for AAA after completing a questionnaire on demographic information and potential risk factors. RESULTS: A total of 122,272 men and 3450 women were successfully screened. An AAA of 3.0 cm or greater in diameter was found in 4.3% of men and 1.0% of women (P <.001). Contrary to a previous report, we did not find suprarenal aortic enlargement accompanying AAA to be more common in women. The principal associations that we have previously reported for AAA in this cohort (age, smoking, family history of AAA, and a negative association with diabetes) were all similar in women compared with men. In age- and smoking-adjusted models, the interaction terms indicated that black race and cancer were more strongly associated with AAA in women than men (P <.05). Height and cerebral vascular disease were also more strongly associated with AAA in women than in men, but these interaction terms did not reach statistical significance (P <.10). Although the other differences were unexpected and require confirmation, the trend toward a stronger association of cerebral vascular disease with AAA in women is consistent with two previous reports. CONCLUSIONS: Despite the much lower prevalence of AAA in women, the most important associations with AAA are similar to those seen in men. Our data provide some support for a previous finding that cerebrovascular disease may be more closely associated with AAA in women than in men.

The aneurysm detection and management study screening program: validation cohort and final results. Aneurysm Detection and Management Veterans Affairs Cooperative Study Investigators.

BACKGROUND: We previously reported the prevalence and associations of abdominal aortic aneurysm (AAA) in 73451 veterans aged 50 to 79 years who underwent ultrasound screening. OBJECTIVE: To understand the prevalence of and principal positive and negative risk factors for AAA, and to assess reproducibility of our previous findings. METHODS: In the new cohort of veterans undergoing screening, 52 745 subjects aged 50 to 79 without history of AAA underwent successful ultrasound screening for AAA, after completing a questionnaire on demographics and potential risk factors. RESULTS: We detected AAA of 4.0 cm or larger in 613 participants (1.2%; compared with 1.4% in the earlier cohort). The direction and magnitude of the important associations reported in the first cohort were confirmed. Respective odds ratios for the major associations with AAA for the second and for the combined cohorts were as follows: 1.81 and 1.71 for age (per 7 years), 0.12 and 0. 18 for female sex, 0.59 and 0.53 for black race, 1.94 and 1.94 for family history of AAA, 4.45 and 5.07 for smoking, 0.50 and 0.52 for diabetes, and 1.60 and 1.66 for atherosclerotic diseases. The excess prevalence associated with smoking accounted for 75% of all AAAs of 4.0 cm or larger in the total population of 126 196. Associations for AAA of 3.0 to 3.9 cm were similar but tended to be somewhat weaker. CONCLUSIONS: Our findings confirm our previous cohort findings. Age, smoking, family history of AAA, and atherosclerotic diseases remained the principal positive associations with AAA, and female sex, diabetes, and black race remained the principal negative associations.

The rational clinical examination. Does this patient have abdominal aortic aneurysm? .

In the physical examination of abdominal aortic aneurysm (AAA), the only maneuver of demonstrated value is abdominal palpation to detect abnormal widening of the aortic pulsation. Palpation of AAA appears to be safe and has not been reported to precipitate rupture. The best evidence on the accuracy of abdominal palpation comes from 15 studies of patients not previously known to have AAA who were screened with both abdominal palpation and ultrasound. When results from these studies are pooled, the sensitivity of abdominal palpation increases significantly with AAA diameter (P<.001), ranging from 29% for AAAs of 3.0 to 3.9 cm to 50% for AAAs of 4.0 to 4.9 cm and 76% for AAAs of 5.0 cm or greater. Positive and negative likelihood ratios with 95% confidence intervals (CIs) using a cutoff point for AAAs of 3.0 cm or greater are 12.0 (95% CI, 7.4-19.5) and 0.72 (95% CI, 0.65-0.81), respectively, and for AAAs of 4.0 cm or greater are 15.6 (95% CI, 8.6-28.5) and 0.51 (95% CI, 0.38-0.67). The positive predictive value of palpation for AAA of 3.0 cm or greater in these studies was 43%. Limited data suggest that abdominal obesity decreases the sensitivity of palpation. Abdominal palpation specifically directed at measuring aortic width has moderate sensitivity for detecting an AAA that would be large enough to be referred for surgery but cannot be relied on to exclude AAA, especially if rupture is a possibility.

Relationship of age, gender, race, and body size to infrarenal aortic diameter. The Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Investigators.

PURPOSE: To assess the effects of age, gender, race, and body size on infrarenal aortic diameter (IAD) and to determine expected values for IAD on the basis of these factors. METHODS: Veterans aged 50 to 79 years at 15 Department of Veterans Affairs medical centers were invited to undergo ultrasound measurement of IAD and complete a pre-screening questionnaire. We report here on 69,905 subjects who had no previous history of abdominal aortic aneurysm (AAA) and no ultrasound evidence of AAA (defined as IAD > or = 3.0 cm). RESULTS: Although age, gender, black race, height, weight, body mass index, and body surface area were associated with IAD by multivariate linear regression (all p < 0.001), the effects were small. Female sex was associated with a 0.14 cm reduction in IAD and black race with a 0.01 cm increase in IAD. A 0.1 cm change in IAD was associated with large changes in the independent variables: 29 years in age, 19 cm or 40 cm in height, 35 kg in weight, 11 kg/m2 in body mass index, and 0.35 m2 in body surface area. Nearly all height-weight groups were within 0.1 cm of the gender means, and the unadjusted gender means differed by only 0.23 cm. The variation among medical centers had more influence on IAD than did the combination of age, gender, race, and body size. CONCLUSIONS: Age, gender, race, and body size have statistically significant but small effects on IAD. Use of these parameters to define AAA may not offer sufficient advantage over simpler definitions (such as an IAD > or = 3.0 cm) to be warranted.

Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group.

BACKGROUND: Independent risk factors for abdominal aortic aneurysm (AAA) have not been clearly defined in multivariable analyses of large patient populations. OBJECTIVE: To identify factors that are independently associated with AAA and to determine the prevalence of previously unrecognized AAA in defined demographic and risk groups. DESIGN: Cross-sectional screening study. SETTING: 15 Department of Veterans Affairs medical centers. PARTICIPANTS: 73451 veterans who were 50 to 79 years of age and had no history of AAA. MEASUREMENTS: The results of ultrasonographic screening for AAA and a prescreening questionnaire were analyzed using multiple logistic regression. RESULTS: An AAA of 4.0 cm or larger was detected in 1031 participants (1.4%). Smoking was the risk factor most strongly associated with AAA; the odds ratio (OR) for AAAs of 4.0 cm or larger compared with normal aortas (infrarenal aortic diameter < 3.0 cm) was 5.57 (95% CI, 4.24 to 7.31). The association between smoking and AAA increased significantly with the number of years of smoking and decreased significantly with the number of years after quitting smoking. The excess prevalence associated with smoking accounted for 78% of all AAAs that were 4.0 cm or larger in the study sample. Female sex (OR, 0.22 [CI, 0.07 to 0.68]), black race (OR, 0.49 [CI, 0.35 to 0.69]), and presence of diabetes (OR, 0.54 [CI, 0.44 to 0.65]) were negatively associated with AAA. A family history of AAA was positively associated with AAA (OR, 1.95 [CI, 1.56 to 2.43]) but was reported by only 5.1% of participants. Other independently associated factors included age, height, coronary artery disease, any atherosclerosis, high cholesterol levels, and hypertension. CONCLUSIONS: Abdominal aortic aneurysm is associated with multiple factors. Smoking was the risk factor most strongly associated with AAA and may be responsible for most clinically important cases of previously undiagnosed AAA.

Risk of rupture of large abdominal aortic aneurysms. Disagreement among vascular surgeons.

BACKGROUND: Many patients with an abdominal aortic aneurysm (AAA) who are cared for by internists are not good candidates for surgery. Elective repair is usually deferred in these patients until the AAA reaches a diameter at which the estimated risk of rupture is believed to outweigh the operative risk. The risk of rupture is usually estimated by a consulting vascular surgeon, but whether these estimates are well-supported or consistent has not previously been assessed. OBJECTIVE: To determine the agreement among vascular surgeons about the risk of rupture of large AAAs. METHODS: All individual members of the Society for Vascular Surgery (Manchester, Mass) residing in the United States were mailed a survey asking for their estimates of the likelihood of rupture of large AAAs. RESULTS: The response rate was 66% and the 257 respondents who reported that they were practicing vascular surgeons constitute the study group. The median estimates of the 1-year risk of rupture were 20% for 6.5-cm AAAs and 30% for 7.5-cm AAAs, with one third of respondents estimating 50% or greater risk of rupture for 7.5-cm AAAs and nearly one third estimating 50% or greater risk of rupture for 6.5-cm AAAs. The responses spanned a wide range and were generally much higher than would be expected based on published data and estimates. CONCLUSIONS: This survey demonstrates profound disagreement among vascular surgeons about the risk of rupture of large AAAs, reflecting a lack of pertinent published data. Better data are necessary and are being collected.

Variability in measurement of abdominal aortic aneurysms. Abdominal Aortic Aneurysm Detection and Management Veterans Administration Cooperative Study Group.

PURPOSE: The purpose of this study was to report interobserver and intraobserver variability of computed tomography (CT) measurements of abdominal aortic aneurysm (AAA) diameter and agreement between CT and ultrasonography observed in the course of a large, multicenter, randomized trial on the management of small AAAs. METHODS: CT measurements of AAA diameter from participating centers were compared with measurements made from the same scan by a central laboratory. Blinded central remeasurement of a randomly selected subset of these CT scans was used to assess intraobserver variability. Agreement between AAA measurements by CT and ultrasonography done within 30 days of each other was also assessed. RESULTS: For interobserver pairs of local and central CT measurements of AAA diameter (n = 806), the difference was 0.2 cm or less in 65% of pairs, but 17% differed by at least 0.5 cm. For intraobserver pairs of central CT remeasurements (n = 70), 90% differed by 0.2 cm or less, 70% were within 0.1 cm, and only one differed by 0.5 cm. Of 258 ultrasound-measured and central CT pairs, the difference was 0.2 cm or less in 44% and at least 0.5 cm in 33%. Ultrasound measurements were smaller than central CT measurements by an average of 0.27 cm (p < 0.0001). Local CT and ultrasound measurements showed a marked preference for recording by half centimeter. CONCLUSIONS: A high degree of precision is possible in CT measurement of AAA diameter, but this precision may not be obtained in practice because of differences in measurement techniques. Differences between imaging modalities increase variability further. Variations in AAA measurement of 0.5 cm or more are not uncommon, and this should be taken into account in management decisions. Efforts to reduce variation in measurement are warranted and might include (1) seeking agreement between surgeons and radiologists on a precise definition of AAA diameter, (2) limiting the number of radiologists who measure AAAs, and (3) use of calipers and magnifying glass for CT measurements.

Lung cancer surgery. A critical review of the evidence.

Surgery is generally considered to be the treatment of choice for anatomically localized non-small-cell lung cancer, but its effectiveness remains unproven. Observational studies have been of limited value because the criteria by which patients are selected for surgery create substantial differences between patients who undergo surgery and those who do not. One small randomized trial of surgery vs radiotherapy was inconclusive, but several large trials of lung cancer screening have provided indirect evidence against a benefit from surgery. Two ongoing randomized trials, one on extensive vs limited resection and the other on the effect of surgery in more extensive disease, may provide further insight into the effectiveness of surgery in the treatment of localized non-small-cell lung cancer. Development of a large randomized trial to directly assess the effectiveness of surgery in the treatment of localized non-small-cell lung cancer has been precluded by ethical concerns, but may need to be reconsidered if indicated by the findings of the two ongoing studies.

Design of the abdominal aortic Aneurysm Detection and Management Study. ADAM VA Cooperative Study Group.

PURPOSE: This study describes the design of an ongoing randomized trial intended to determine which of two strategies is superior for managing small abdominal aortic aneurysms (AAA). METHODS: Patients aged 50 to 79 years with AAA 4.0 to 5.4 cm in diameter as determined by computed tomography (CT) who are not at high surgical risk are randomized to either repair of the AAA, called "immediate surgery," or follow-up of the AAA with ultrasonography or CT every 6 months, reserving surgery for those aneurysms that enlarge to 5.5 cm, enlarge rapidly, or become symptomatic, called "selective surgery." RESULTS: The primary outcome measure is all-cause death, and secondary outcome measures are AAA-related death, morbidity, and general health status. The study design calls for 1350 patients to be randomized and monitored for a mean of 5 years. A second objective of the study is to accurately define the prevalence and risk factors for AAA with use of information from the large screening program established to detect AAA for recruitment into the randomized trial. CONCLUSIONS: By the end of 1993, 38,697 patients had been screened with ultrasonography, accounting for about three fourths of new randomizations, and 330 patients had been enrolled (70% of the target rate).

Ruptured abdominal aortic aneurysm: the internist as diagnostician.

PURPOSE: To define the clinical features and assess the frequency and causes of missed diagnoses of ruptured abdominal aortic aneurysm (AAA) in patients initially presenting to internists. PATIENTS: All identified patients with ruptured AAA presenting to internists during a 7 1/2-year period at a large academic medical center. METHOD: Chart review. RESULTS: We identified 23 patients with a ruptured AAA presenting to internists. Most had abdominal pain and tenderness, back or flank pain, and leukocytosis, whereas anemia and profound hypotension (systolic blood pressure below 90 mm Hg) were uncommon at presentation. In 14 cases (61%), the diagnosis of ruptured AAA was initially missed. Nine patients had an interval of 24 hours or more between presentation to the internist and surgery or death. The diagnosis was not made until after shock developed in nine patients who were hemodynamically stable at presentation. Of 17 patients who underwent surgery, 7 of 8 with preoperative shock died, compared with 2 deaths in 9 patients (p < .02) without shock. All six patients who did not have surgery died, yielding an overall mortality of 65% for the series. Ruptured AAAs were most frequently misdiagnosed as urinary tract obstruction or infection, spinal disease, and diverticulitis. Chart review revealed a general lack of physician awareness of the syndromes of contained rupture of AAA and symptomatic unruptured AAA. CONCLUSIONS: In patients with ruptured AAA who present to internists, the diagnosis is often delayed or missed and this appears to adversely effect survival. Internists should familiarize themselves with the presentation and management of ruptured AAA.