A Danish, single-centre trial has suggested that mass screening for abdominal aortic aneurysms in men aged 65+ years saves lives. The study, published in the British Medical Journal, found that one life was saved for every 352 men, four years after undergoing abdominal ultrasonography. Lead investigator, Dr Jes Lindholt (Sygehus Viborg, Denmark) said ruptured abdominal aortic aneurysms occur in about 1-3% of men aged at least 65 years, with at least three-quarters dying as a result. In contrast, death rates from elective abdominal aortic aneurysm surgery are just 5-7%. However, abdominal aortic aneurysm seldomly causes symptoms before rupture, so screening seems worthwhile considering. Consequently, the team randomly assigned 12,639 men from Viborg County, Denmark, who turned 65 years of age in 1995-8 to receive an invitation for ultrasound screening or no such invitation. The patients were randomly assigned to either screening (n=6,333) or the control group (n=6,306).
Participants in the screening group underwent abdominal ultrasonography at their regional hospital. Non-responders were re-invited once. Scanning (B mode) was carried out by a specially trained doctor and nurse using a Phillips SDR 1550 device with linear 4 MHz transducer and calliper light pen. Participants were not required to fast. Intervention participants with abdominal aortic aneurysms of >5cm or more were referred for surgical evaluation, while those with smaller aneurysms were offered annual scans.
The primary outcome measures were specific mortality due to abdominal aortic aneurysm, total mortality, number of operations and indications for operations, and number of ruptured aneurysms. Data on operations were obtained from the patients' records. The researchers obtained data on deaths occurring from April 1994 to December 1999 through the Danish civil register and causes of death through the national register of causes of death. Hospital records and autopsy records of patients whose death certificates stated abdominal aortic aneurysm as the primary or contributing cause of death were obtained and assessed by two vascular surgeons who were blinded to the randomisation group and to each other's evaluations.
Each assessed the deaths to be certainly, possibly, or not caused by abdominal aortic aneurysm. The deaths were considered to be due to abdominal aortic aneurysm when both assessors evaluated the death as certainly or possibly caused by such aneurysms. Analyses were performed on "intention to screen" basis.
A total of 4,860 of 6,333 men were screened (attendance rate 76.6%). 191 (4.0% of those screened) had abdominal aortic aneurysm. The mean follow-up time was 52 months.
After 3-5 years, the 162 survivors with an aorta diameter initially sized at 25-29mm were offered re-screening as were a random sample of 275 survivors with an aorta initially sized at less than <25mm. More than 80% attended re-screening. Whereas none of the controls had developed abdominal aortic aneurysms, 28% of those with an initially sized aorta of 25-29mm developed an aneurysm, with three participants later referred for surgical evaluation. Consequently, Lindholt concluded, "Re-screening patients with an aortic diameter of less than 25mm seems unwarranted, whereas patients with pre-aneurysms of 25-29mm in diameter should be re-screened after five years."
The screened group underwent significantly fewer emergency procedures than the control group (75.0%, 50.9% to 91.3%). Overall, 59 participants were operated on electively: 48 in the screened group and 11 in the control group. Of these, three (two in the screened group) died within 30 days postoperatively (5.1%). A fourth died 2.5 months postoperatively due to complications.
Of those referred for surgery after screening, two died before surgery, one due to ruptured abdominal aortic aneurysm (surgery had to be postponed because of acute myocardial infarction) and the other due to ruptured iliac aneurysms. Furthermore, three participants with abdominal aortic aneurysm in the screened group who were recommended for surgery died of ruptured aneurysm; one initially had contraindications for surgery one refused surgery, and one did not attend for follow-up.
Sixteen of the 37 patients with recognised rupture underwent surgery (43.2%), 10 of whom died (62.5%). Overall, the case fatality due to ruptured abdominal aortic aneurysm was 86.1% (64.8% to 92.0%), and the incidence of recognised ruptured aneurysms in the control group was 1.07 per 1000 observation years.
Nine participants in the screened group died from abdominal aortic aneurysm compared with 27 in the control group (hazard ratio 0.33, 0.16 to 0.71). During the 18 months after randomisation, the two groups showed similar mortality due to abdominal aortic aneurysm (0.77, 0.29 to 2.07), but thereafter mortality was lower in the screened group (0.11, 0.03 to 0.48).
In the screened group, all cause mortality was insignificantly decreased (hazard ratio 0.92, 0.84 to 1.00) and mortality from causes other than abdominal aortic aneurysm was also insignificantly decreased (0.92, 0.85 to 1.02). The number of life years gained by offering 6,333 men screening was 32 (14 to 49) during the first five years. If the prediction was extended to 10 and 15 years, the number of life years gained was 107 (48 to 164) and 158 (71 to 244), respectively. Total mortality among non-attenders for screening was significantly higher than that among those who did attend for screening (hazard ratio 1.98, 1.73 to 2.26).
The researchers calculated the expected number of life years gained within five, 10, and 15 years for two hypothetical cohorts representing screened participants and controls, each of 6,333 men aged 67. In the cohort representing the controls, it was estimated the number of remaining life years from the life table for Danish men in 1995 and 1996. In the cohort representing the screened participants, it was assumed the mortality for the period 1.5 to five years after randomisation to be reduced by the difference in specific mortality due to abdominal aortic aneurysm per 1000 years in the study (0.89, 95% confidence interval 0.40 to 1.37); before 1.5 years and after five years assumed that the mortality was unaffected by screening.
The researchers selected this interval because of unproportional hazards in the whole period, and lack of a preventive effect until 1.5 years after randomisation. The observed age specific mortality among controls was close to Danish men in 1995 and 1996, but because they observed the controls for less than six years they could not use their data for projections beyond that.
Screening Danish men aged 64-73 for abdominal aortic aneurysm reduced the need for emergency operations by 75% and reduced specific mortality due to such aneurysms by 67%. It is possible that some deaths may have been misclassified as due to abdominal aortic aneurysm, as autopsy was carried out in only 6% of the participants. However, 43% of the patients with ruptured aneurysm underwent surgery, providing enough data for evaluation. Furthermore, the two vascular surgeons disagreed on only three cases of death from hospital and autopsy reports. The assessors were blinded to group allocation and therefore classification bias seems unlikely.
Surprisingly, no deaths were observed due to abdominal aortic aneurysm in the screened group after 28 months. The number of elective procedures decreased rapidly after the first two years and therefore attenders were at low risk of deaths due to such surgery. Only four deaths due to abdominal aortic aneurysm occurred among non-attenders; the difference from the expected number, however, was not significant and could be coincidental the researchers claim. Alternatively, selection could be an explanation, as previous studies on this population have shown that those with diseases related to abdominal aortic aneurysms attend screening more often than those without, so the prevalence of such aneurysms among non-attenders could be expected to be lower than among attenders. However, the lower frequency of diseases related to abdominal aortic aneurysm among non-attenders was not associated with better survival.
The researchers acknowledge that the main results are limited to a relatively short observation period. This is a conservative way to interpret the results, because benefits are expected to increase with time. They estimated the future benefits in terms of life years gained in 15 years. The main assumptions behind the estimates were conservative: that mortality not due to abdominal aortic aneurysm is unaffected by screening and that screening has a net effect on mortality due to abdominal aortic aneurysm only between 1.5 and five years after screening, with difference in mortality due to such aneurysms per 1000 years of 0.89 (0.40 to 1.37), as observed in the present study. After five years, mortality due to abdominal aortic aneurysm was assumed to be unaffected by screening.
The investigators claim this probably an underestimation of the benefits, since the incidence of ruptured abdominal aortic aneurysms increases with age, although the frequency of non-compliance among patients with a conservatively treated aneurysm and those unfit for surgery will probably also increase with age.
In the UK multicentre aneurysm screening study, the relative risk reduction was 42% (95% confidence interval 22% to 58%). Although lower than in this study, this value is not significantly different from the 67% observed.
In Western Australia, a randomised trial among men aged 65-83 showed an insignificant relative risk of death due to abdominal aortic aneurysm in the intervention group of 0.61 (95% confidence interval 0.33 to 1.11), but among the men aged 65-74 who were originally intended as participants the relative risk was significant (0.19, 0.04 to 0.89).
Noting that the Danish results are consistent with the other studies in the UK and Western Australia, Lindholt et al. conclude that mass screening for abdominal aortic aneurysms appears to reduce mortality and called for further studies to analyse whether screening is cost effective in Denmark and Western Australia.
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