Population based randomised controlled trial on impact of screening on mortality from abdominal aortic aneurysm
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《英国医生杂志》
1 School of Surgery and Pathology, University of Western Australia, Fremantle Hospital, PO Box 480, Fremantle, WA 6959, Australia, 2 School of Population Health, University of Queensland, Herston, QLD 4006, Australia, 3 Mount Medical Centre, Perth, WA 6005, Australia, 4 School of Population Health, University of Western Australia, Crawley, WA 6009, Australia, 5 Department of Family Medicine, University of Calgary, AB, Canada T2N 1M7
Correspondence to: P Norman pnorman@cyllene.uwa.edu.au
Abstract
Despite advances in vascular surgery and intensive care, the overall case fatality of rupture of an abdominal aortic aneurysm is still around 80%.1 In addition, the incidence of such events seems to have risen over the past two decades.2-4 This contrasts with trends seen in coronary heart disease and stroke, suggesting that measures introduced to reduce the impact of occlusive arterial disease have not been effective.
The feasibility of population based screening for such aneurysms by using ultrasound has been established over the past 15 years.5-7 These early studies generated considerable debate about the merits of population screening, resulting in calls for randomised controlled trials.8-10 In the first such trial, Scott et al reported a large (50%) but non-significant reduction in mortality with screening.11 Since then two randomised trials and several non-randomised studies have all indicated that screening in men saves lives cost effectively.12-16 We designed a trial to complement these, focusing on men aged 65 to 74 years but also including an older group.
The Western Australia trial of screening for abdominal aortic aneurysms is a population based randomised controlled trial to determine whether a single ultrasound screen for abdominal aortic aneurysms17 reduces deaths among those to whom it is offered. The trial was designed to cover an entire metropolitan community and assess the effectiveness of introducing population screening into an existing healthcare system. Western Australia is an ideal location for such a trial: the population is geographically isolated and stable, all deaths and hospital admissions are linked within a unified database system, and much is already known about local trends and outcomes for abdominal aortic aneurysm.1 3 18 19 Here we report on the early effect of screening on mortality in the trial.
Methods
Figure 1 shows the flow of participants through the study. The 41 000 men randomised to the two groups were balanced for age (mean (SD) 72.6 (4.7) v 72.6 (4.7) years). Screening was completed over a period of 32 months, and the median follow up was 43 (range 27-61) months. Because of the method of recording age in the electoral roll, some men were older than the target age range by the time they were invited for screening and, as a result, 725 (5.9%) of those who attended were aged 80-83 years.17
Fig 1 Summary of trial of screening for abdominal aortic aneurysm
Participation in screening and prevalence of abdominal aortic aneurysm
There was no difference between the numbers of men in the two groups who had had surgery for abdominal aortic aneurysm before scheduled screening (table 1, P = 0.47, 2test). Within the men invited for screening, the prevalence of previous surgery for abdominal aortic aneurysm was highest among those who did not attend (2.7%). Similar numbers of men in the two groups died between randomisation and scheduled screening, including 25 deaths from rupture (13 in invited group, 12 in control group). After correcting the lists for deaths, we sent letters of invitation to 19 352 men. Of these, 12 213 underwent a screening examination, a crude response fraction of 63.1%. If we excluded 1836 men who would generally be considered ineligible this figure increased to 70% (fig 1).
Table 1 Elective and emergency procedures for abdominal aortic aneurysm before scheduled screening
The overall crude prevalence of any aortic aneurysms (aorta 30 mm) was 7.2%, increasing from 4.8% in men aged 65-69 years to 10.8% in the oldest men. Of the 875 cases detected, 699 (80%) aortas were 30-44 mm in diameter, 115 (13%) were 45-54 mm in diameter, and 61 (7%) were 55 mm in diameter.17
Procedures and deaths after scheduled screening
Table 2 shows the numbers of procedures for and deaths from abdominal aortic aneurysm after scheduled screening. Table 3 shows the corresponding numbers of events that occurred between randomisation and the end of follow up. The overall mortality within 30 days was 4.3% (7/161) after elective surgery and 24% (4/17) after surgery for ruptured aneurysms (table 2), with no difference between study groups (P = 0.59, 2 test). Twice as many men in the intervention group underwent elective surgery for abdominal aortic aneurysm compared with the number in the control group (107 v 54, P = 0.002, 2 test).
Table 2 Elective and emergency procedures and crude and age standardised mortality from abdominal aortic aneurysm between scheduled screening and the end of follow up
Table 3 Elective and emergency procedures, deaths, and crude and age standardised mortality from abdominal aortic aneurysm between randomisation and the end of follow up
Between scheduled screening and the end of follow up 18 men died from abdominal aortic aneurysm in the intervention group and 25 in the control group (table 2), yielding a mortality rate ratio of 0.61 (95% confidence interval 0.33 to 1.11). The age standardised mortality for those who actually attended screening was 60% lower than in the control group (7.48 v 18.91 deaths per 100 000 man years, table 2). Between randomisation and the end of follow up there were 31 deaths from abdominal aortic aneurysm in the intervention group and 37 in the control group, yielding a mortality rate ratio of 0.85 (0.53 to 1.36, table 3). Figures 2 and 3 show the cumulative mortality from abdominal aortic aneurysm. Men in the intervention group initially had a higher mortality, but after one year the mortality curves crossed, such that the difference between them was not significant.
Fig 2 Cumulative mortality due to abdominal aortic aneurysm after date of screening
Fig 3 Cumulative mortality due to abdominal aortic aneurysm after date of randomisation
Table 4 summarises the mortality from abdominal aortic aneurysm in men aged 65-74 years and 75 years. There were no deaths among men aged 65-74 years who underwent screening and only two deaths (after scheduled screening) among those who were invited but did not attend compared with 10 in the control group, an odds ratio of 0.19 (0.04 to 0.89, P = 0.01). When we included deaths between randomisation and scheduled screening, however, we found no benefit in the younger age group (odds ratio 0.82, 0.37 to 1.84, P = 0.6).
Table 4 Cumulative mortality from abdominal aortic aneurysm in men aged 64-75 years and 75 years
Table 5 and figures 4 and 5 show the cumulative and age standardised all cause mortality. There is clear evidence of response bias among men who took up the invitation to be screened; their mortality experience was close to half that of invited men who did not undergo a scan. Overall, however, there were no meaningful differences in the age standardised mortality rates for all causes for the invited and control groups.
Table 5 Cumulative and age standardised all cause mortality over five years after real or virtual date of screening
Fig 4 Cumulative all cause mortality after date of screening
Fig 5 Cumulative all cause mortality from date of randomisation
Discussion
Semmens J, Lawrence-Brown M, Norman P, Codde J, Holman C. The quality of surgical care project: benchmark standards of open resection for abdominal aortic aneurysm in Western Australia. Aust N Z J Surg 1998;68: 404-10.
Fowkes FGR, Macintyre CCA, Ruckley CV. Increasing incidence of aortic aneurysms in England and Wales. BMJ 1989;298: 33-5.
Semmens JB, Norman PE, Lawrence-Brown MMD, Bass AJ, Holman CDJ. The incidence of abdominal aortic aneurysm repair in Western Australia for 1985-94: a population-based record linkage study. Br J Surg 1998;87: 191-4.
Reitsma JB, Pleumeekers HJCM, Hoes AW, Kleijnen J, de Groot RM, Jacobs MJ, et al. Increasing incidence of aneurysms of the abdominal aorta in the Netherlands. Eur J Vasc Endovasc Surg 1996;12: 446-51.
Scott RAP, Ashton HA, Kay DN. Abdominal aortic aneurysm in 4237 screened patients: prevalence development and management over 6 years. Br J Surg 1991;78: 1122-5.
Collin J, Araujo L, Walton J, Lindsell D. Oxford screening programme for abdominal aortic aneurysm in men aged 65 to 74 years. Lancet 1988;ii: 613-5.
Lederle FA, Johnson GR, Wilson SE, Chute EP, Littooy FN, Bandyk D, et al. Prevalence and associations of abdominal aortic aneurysm detected through screening. Ann Intern Med 1997;126: 441-9.
Harris P. Reducing the mortality from abdominal aortic aneurysms: need for a national screening programme. BMJ 1992;305: 697-9.
Fowkes F, Ruckley C, Powell J, Greenhalgh R. Screening for abdominal aortic aneurysms. BMJ 1992;305: 1013.
Cheatle TR. The case against a national screening programme for aortic aneurysms. Ann R Coll Surg Engl 1997;79: 90-5.
Scott RAP, Wilson NM, Ashton HA, Kay DN. Influence of screening on the incidence of ruptured abdominal aortic aneurysm: 5-year results of a randomised controlled study. Br J Surg 1995;82: 1066-70.
Wilmink T, Quick C, Hybbard C, Day N. The influence of screening on the incidence of ruptured abdominal aortic aneurysms. J Vasc Surg 1999;30: 203-8.
Heather B, Poskitt K, Earnshaw J, Whyman M, Shaw E. Population screening reduces mortality rate from aortic aneurysm in men. Br J Surg 2000;87: 750-3.
Lindholt J, Juul S, Fasting H, Henneberg E. Hospital costs and benefits of screening for abdominal aortic aneurysms. Results from a randomised population screening trial. Eur J Vasc Endovas Surg 2002;23: 55-60.
Multicentre Aneurysm Screening Study Group. The multicentre aneurysm screening study into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial. Lancet 2002;360: 1531-39.
Multicentre Aneurysm Screening Study Group. Multicentre aneurysm screening study: cost effectiveness analysis of screening for abdominal aortic aneurysms based on four year results from randomised controlled trial. BMJ 2002;325: 1135-8.
Jamrozik K, Norman PE, Spencer CA, Parsons RW, Tuohy R, Lawrence-Brown MM, et al. Screening for abdominal aortic aneurysms: lessons from a population-based study. Med J Aust 2000;173: 345-50.
Nicholls EA, Norman PE, Lawrence-Brown MD, Goodman MA, Pedersen B. Screening for abdominal aortic aneurysms in Western Australia. Aust N Z J Surg 1992;62: 858-61.
Norman P, Semmens J, Lawrence-Brown M, Holman C. Long term relative survival after surgery for abdominal aortic aneurysm in Western Australia: population based study. BMJ 1998;317: 852-6.(Paul E Norman, associate )
Correspondence to: P Norman pnorman@cyllene.uwa.edu.au
Abstract
Despite advances in vascular surgery and intensive care, the overall case fatality of rupture of an abdominal aortic aneurysm is still around 80%.1 In addition, the incidence of such events seems to have risen over the past two decades.2-4 This contrasts with trends seen in coronary heart disease and stroke, suggesting that measures introduced to reduce the impact of occlusive arterial disease have not been effective.
The feasibility of population based screening for such aneurysms by using ultrasound has been established over the past 15 years.5-7 These early studies generated considerable debate about the merits of population screening, resulting in calls for randomised controlled trials.8-10 In the first such trial, Scott et al reported a large (50%) but non-significant reduction in mortality with screening.11 Since then two randomised trials and several non-randomised studies have all indicated that screening in men saves lives cost effectively.12-16 We designed a trial to complement these, focusing on men aged 65 to 74 years but also including an older group.
The Western Australia trial of screening for abdominal aortic aneurysms is a population based randomised controlled trial to determine whether a single ultrasound screen for abdominal aortic aneurysms17 reduces deaths among those to whom it is offered. The trial was designed to cover an entire metropolitan community and assess the effectiveness of introducing population screening into an existing healthcare system. Western Australia is an ideal location for such a trial: the population is geographically isolated and stable, all deaths and hospital admissions are linked within a unified database system, and much is already known about local trends and outcomes for abdominal aortic aneurysm.1 3 18 19 Here we report on the early effect of screening on mortality in the trial.
Methods
Figure 1 shows the flow of participants through the study. The 41 000 men randomised to the two groups were balanced for age (mean (SD) 72.6 (4.7) v 72.6 (4.7) years). Screening was completed over a period of 32 months, and the median follow up was 43 (range 27-61) months. Because of the method of recording age in the electoral roll, some men were older than the target age range by the time they were invited for screening and, as a result, 725 (5.9%) of those who attended were aged 80-83 years.17
Fig 1 Summary of trial of screening for abdominal aortic aneurysm
Participation in screening and prevalence of abdominal aortic aneurysm
There was no difference between the numbers of men in the two groups who had had surgery for abdominal aortic aneurysm before scheduled screening (table 1, P = 0.47, 2test). Within the men invited for screening, the prevalence of previous surgery for abdominal aortic aneurysm was highest among those who did not attend (2.7%). Similar numbers of men in the two groups died between randomisation and scheduled screening, including 25 deaths from rupture (13 in invited group, 12 in control group). After correcting the lists for deaths, we sent letters of invitation to 19 352 men. Of these, 12 213 underwent a screening examination, a crude response fraction of 63.1%. If we excluded 1836 men who would generally be considered ineligible this figure increased to 70% (fig 1).
Table 1 Elective and emergency procedures for abdominal aortic aneurysm before scheduled screening
The overall crude prevalence of any aortic aneurysms (aorta 30 mm) was 7.2%, increasing from 4.8% in men aged 65-69 years to 10.8% in the oldest men. Of the 875 cases detected, 699 (80%) aortas were 30-44 mm in diameter, 115 (13%) were 45-54 mm in diameter, and 61 (7%) were 55 mm in diameter.17
Procedures and deaths after scheduled screening
Table 2 shows the numbers of procedures for and deaths from abdominal aortic aneurysm after scheduled screening. Table 3 shows the corresponding numbers of events that occurred between randomisation and the end of follow up. The overall mortality within 30 days was 4.3% (7/161) after elective surgery and 24% (4/17) after surgery for ruptured aneurysms (table 2), with no difference between study groups (P = 0.59, 2 test). Twice as many men in the intervention group underwent elective surgery for abdominal aortic aneurysm compared with the number in the control group (107 v 54, P = 0.002, 2 test).
Table 2 Elective and emergency procedures and crude and age standardised mortality from abdominal aortic aneurysm between scheduled screening and the end of follow up
Table 3 Elective and emergency procedures, deaths, and crude and age standardised mortality from abdominal aortic aneurysm between randomisation and the end of follow up
Between scheduled screening and the end of follow up 18 men died from abdominal aortic aneurysm in the intervention group and 25 in the control group (table 2), yielding a mortality rate ratio of 0.61 (95% confidence interval 0.33 to 1.11). The age standardised mortality for those who actually attended screening was 60% lower than in the control group (7.48 v 18.91 deaths per 100 000 man years, table 2). Between randomisation and the end of follow up there were 31 deaths from abdominal aortic aneurysm in the intervention group and 37 in the control group, yielding a mortality rate ratio of 0.85 (0.53 to 1.36, table 3). Figures 2 and 3 show the cumulative mortality from abdominal aortic aneurysm. Men in the intervention group initially had a higher mortality, but after one year the mortality curves crossed, such that the difference between them was not significant.
Fig 2 Cumulative mortality due to abdominal aortic aneurysm after date of screening
Fig 3 Cumulative mortality due to abdominal aortic aneurysm after date of randomisation
Table 4 summarises the mortality from abdominal aortic aneurysm in men aged 65-74 years and 75 years. There were no deaths among men aged 65-74 years who underwent screening and only two deaths (after scheduled screening) among those who were invited but did not attend compared with 10 in the control group, an odds ratio of 0.19 (0.04 to 0.89, P = 0.01). When we included deaths between randomisation and scheduled screening, however, we found no benefit in the younger age group (odds ratio 0.82, 0.37 to 1.84, P = 0.6).
Table 4 Cumulative mortality from abdominal aortic aneurysm in men aged 64-75 years and 75 years
Table 5 and figures 4 and 5 show the cumulative and age standardised all cause mortality. There is clear evidence of response bias among men who took up the invitation to be screened; their mortality experience was close to half that of invited men who did not undergo a scan. Overall, however, there were no meaningful differences in the age standardised mortality rates for all causes for the invited and control groups.
Table 5 Cumulative and age standardised all cause mortality over five years after real or virtual date of screening
Fig 4 Cumulative all cause mortality after date of screening
Fig 5 Cumulative all cause mortality from date of randomisation
Discussion
Semmens J, Lawrence-Brown M, Norman P, Codde J, Holman C. The quality of surgical care project: benchmark standards of open resection for abdominal aortic aneurysm in Western Australia. Aust N Z J Surg 1998;68: 404-10.
Fowkes FGR, Macintyre CCA, Ruckley CV. Increasing incidence of aortic aneurysms in England and Wales. BMJ 1989;298: 33-5.
Semmens JB, Norman PE, Lawrence-Brown MMD, Bass AJ, Holman CDJ. The incidence of abdominal aortic aneurysm repair in Western Australia for 1985-94: a population-based record linkage study. Br J Surg 1998;87: 191-4.
Reitsma JB, Pleumeekers HJCM, Hoes AW, Kleijnen J, de Groot RM, Jacobs MJ, et al. Increasing incidence of aneurysms of the abdominal aorta in the Netherlands. Eur J Vasc Endovasc Surg 1996;12: 446-51.
Scott RAP, Ashton HA, Kay DN. Abdominal aortic aneurysm in 4237 screened patients: prevalence development and management over 6 years. Br J Surg 1991;78: 1122-5.
Collin J, Araujo L, Walton J, Lindsell D. Oxford screening programme for abdominal aortic aneurysm in men aged 65 to 74 years. Lancet 1988;ii: 613-5.
Lederle FA, Johnson GR, Wilson SE, Chute EP, Littooy FN, Bandyk D, et al. Prevalence and associations of abdominal aortic aneurysm detected through screening. Ann Intern Med 1997;126: 441-9.
Harris P. Reducing the mortality from abdominal aortic aneurysms: need for a national screening programme. BMJ 1992;305: 697-9.
Fowkes F, Ruckley C, Powell J, Greenhalgh R. Screening for abdominal aortic aneurysms. BMJ 1992;305: 1013.
Cheatle TR. The case against a national screening programme for aortic aneurysms. Ann R Coll Surg Engl 1997;79: 90-5.
Scott RAP, Wilson NM, Ashton HA, Kay DN. Influence of screening on the incidence of ruptured abdominal aortic aneurysm: 5-year results of a randomised controlled study. Br J Surg 1995;82: 1066-70.
Wilmink T, Quick C, Hybbard C, Day N. The influence of screening on the incidence of ruptured abdominal aortic aneurysms. J Vasc Surg 1999;30: 203-8.
Heather B, Poskitt K, Earnshaw J, Whyman M, Shaw E. Population screening reduces mortality rate from aortic aneurysm in men. Br J Surg 2000;87: 750-3.
Lindholt J, Juul S, Fasting H, Henneberg E. Hospital costs and benefits of screening for abdominal aortic aneurysms. Results from a randomised population screening trial. Eur J Vasc Endovas Surg 2002;23: 55-60.
Multicentre Aneurysm Screening Study Group. The multicentre aneurysm screening study into the effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial. Lancet 2002;360: 1531-39.
Multicentre Aneurysm Screening Study Group. Multicentre aneurysm screening study: cost effectiveness analysis of screening for abdominal aortic aneurysms based on four year results from randomised controlled trial. BMJ 2002;325: 1135-8.
Jamrozik K, Norman PE, Spencer CA, Parsons RW, Tuohy R, Lawrence-Brown MM, et al. Screening for abdominal aortic aneurysms: lessons from a population-based study. Med J Aust 2000;173: 345-50.
Nicholls EA, Norman PE, Lawrence-Brown MD, Goodman MA, Pedersen B. Screening for abdominal aortic aneurysms in Western Australia. Aust N Z J Surg 1992;62: 858-61.
Norman P, Semmens J, Lawrence-Brown M, Holman C. Long term relative survival after surgery for abdominal aortic aneurysm in Western Australia: population based study. BMJ 1998;317: 852-6.(Paul E Norman, associate )