Abdominal Aortic Aneurysm — Open versus Endovascular Repair
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《新英格兰医药杂志》
The publication in this issue of the Journal of the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial1 and the recent publication of a similar study from the United Kingdom2 provide the first randomized comparisons of the endovascular and open techniques for elective repair of abdominal aortic aneurysms. Elective repair is undertaken to prevent the rupture of aneurysms, which carries a mortality rate of about 80 percent. More than 40,000 procedures are performed each year in the United States. Open surgical repair, in which the aneurysm is opened and a graft sewn into place under direct vision, has proved durable in both senses: it has been in use for more than 50 years, and the rate of graft failure is only about 0.3 percent per year.3,4,5 It is, however, major surgery performed in frail, elderly patients with a high rate of complications, a mortality rate that is not negligible, and a recovery time of several months.
Endovascular repair was developed to provide a less traumatic alternative. Endovascular grafts are positioned inside the aneurysm under radiologic guidance and secured with hooks or pressure to shield the segment containing the aneurysm from the blood pressure. The advent of endovascular repair has not been without controversy. After deciding to accept nonrandomized studies of effectiveness, the Food and Drug Administration (FDA) approved two graft systems in 1999, one of which was subsequently withdrawn, and has approved two more since then. Though endovascular repair has been extolled by many as the wave of the future, its brief but clamorous history has also been marked by FDA warnings and allegations of fraud, an editorial denouncing the procedure6 as a "failed experiment," and most recently, industry threats of legal action to block publication of an unfavorable FDA report.7
Nearly all studies have found that, as compared with open repair, endovascular repair results in reduced rates of operative morbidity, a shorter initial hospital stay, and shorter recovery time. Somewhat surprising, though, is that early studies found no improvement in operative mortality rates. That this has changed can be seen most dramatically in statewide data from New York over three years.8 In 2000, the rate of operative mortality for endovascular repair (3.1 percent) was similar to that for open repair (4.1 percent), but during the next two years, while the mortality rate associated with open repair remained unchanged, the rate for endovascular repair dropped to 1 percent. These rates were confirmed by a study of the 2001 Nationwide Inpatient Sample,9 which reported rates of operative mortality of 3.8 percent for open repair and 1.3 percent for endovascular repair.
Nevertheless, even large population-based observational studies can be biased by differences between treatment groups. Elective open repair is not offered to patients at high risk for operative complications, and endovascular repair is limited to patients who have a suitable segment of normal aorta below the renal arteries and who also have iliac arteries free of excessive plaque or tortuosity. Since the resulting differences between treatment groups could obviously affect outcomes, the reports from the two new randomized trials are welcome additions.
The DREAM trial investigators observed substantial reductions in the primary outcome of operative (30-day) morbidity and mortality with endovascular repair, as compared with open repair, that did not reach statistical significance owing to the relatively small sample size. The reduction in operative mortality with endovascular repair in the DREAM trial, from 4.6 percent to 1.2 percent, was very similar to the findings of the larger trial in the United Kingdom.2 That study, the Endovascular Aneurysm Repair (EVAR) trial, randomized 1082 patients and reported a significant reduction in operative mortality with endovascular versus open repair, from 4.7 percent to 1.7 percent. The remarkable agreement among the two population-based observational studies and the two trials leaves little doubt that endovascular repair is now associated with reduced rates of operative mortality and morbidity and a shorter initial hospital stay as compared with the rates for open repair.
Should we then accept the conclusion of the DREAM authors that "endovascular repair is preferable to open repair"? I believe we should not, because operative morbidity and mortality rates represent only half the equation; they address the risk associated with repair, but not the benefit. The more innocuous therapy is favored in a comparison of procedural complications, even if that therapy is ineffective. Just as we would not compare angioplasty and coronary bypass without considering subsequent cardiac events, we cannot compare open repair with endovascular repair without evaluating the long-term risk of aneurysm rupture and graft complications. There is reason to be cautious in this arena. Two large European registries have reported a failure rate for endovascular grafts of 3 percent per year (1 percent for rupture plus 2 percent for conversion to open repair), which is 10 times the failure rate of 0.3 percent for open repair, noted above, and a total secondary-intervention rate of 10 percent per year.10,11,12 Although potentially biased by substantial losses to follow-up, these registries are probably the best source available. The conclusion of the suppressed FDA report was that the total aneurysm-related mortality rate will probably be higher with endovascular repair than with open repair when late deaths are included.7
The late complications after endovascular repair have other important implications, such as the universal requirement for follow-up computed tomography each year for the rest of the patient's life — which is proving to be a considerable burden for both patients and physicians. Another may be the loss within one year of the initial advantage over open repair in the total number of days spent in the hospital.13 Recent reports from one of the registries14 and from the Cleveland Clinic15 raise yet another concern: long-term results after endovascular repair appear to be much worse for larger aneurysms, the ones most in need of repair. The four-year postoperative rupture rate in the registry study14 was 10 percent for abdominal aortic aneurysms measuring 6.5 cm or more in diameter at the time of endovascular repair, as compared with 2 percent for smaller aneurysms. Two years after endovascular repair in the Cleveland series, 6.1 percent of patients with abdominal aortic aneurysms that measured 5.5 cm or larger had aneurysm-related deaths, and 8.2 percent required conversion to open repair, as compared with 1.5 percent and 1.4 percent, respectively, of those with aneurysms measuring less than 5.5 cm.15
These findings are of particular concern because the aspect of the management of abdominal aortic aneurysms for which there is the most certainty, on the basis of results of two large trials,5,16 is the lack of benefit from repair of aneurysms smaller than 5.5 cm. Because the rupture rate of abdominal aortic aneurysms smaller than 5.5 cm that were followed with imaging surveillance was no more than 1 percent per year in those trials, it is unlikely that any treatment will be proved significantly better than surveillance for these patients. Nevertheless, the enthusiasm (aided by marketing and turf battles) surrounding endovascular repair has increased the temptation to repair smaller aneurysms. Forty-five percent of the registry patients and nearly 60 percent of the Cleveland patients who were treated with endovascular repair had aneurysms smaller than 5.5 cm.14,15
No comparison of treatments can be complete without consideration of cost. Despite the reduced rate of operative morbidity and the shorter hospital stay, numerous studies have found endovascular repair to be more expensive than open repair, primarily because of the high price of the grafts (about $13,000 per patient). The extra cost attributable to the use of endovascular repair in place of open repair in the United States in 2001 alone has been estimated at more than $50 million.9
The authors of the EVAR trial wisely advise us that the new findings should be considered "a license to continue scientific evaluation of , but not to change clinical practice" until evidence from trials is available for long-term outcomes.2 The EVAR trial should provide a first look at this evidence as early as next year, with more evidence to follow from the DREAM trial, the Veterans Affairs Open versus Endovascular Repair (OVER) trial, and the French Anévrisme de l'aorte abdominale: Chirurgie versus Endoprothèse (ACE) trial. Even if these trials show endovascular repair to be superior after several years of follow-up, the best treatment for younger patients will remain uncertain until we know how endovascular repair fares over decades. In addition, "small incision" and laparoscopic techniques have been developed, and further studies will be needed to clarify their roles.
Meanwhile, patient management should be guided by what we already know. Small aneurysms should be kept under surveillance with periodic ultrasonographic measurements — every two to three years for those smaller than 4.0 cm, and every six months for larger aneurysms. Elective repair should be considered for abdominal aortic aneurysms measuring 5.5 cm or larger. If the patient is a candidate for either open or endovascular repair, referral to a randomized trial is the best option.
Source Information
From the Center for Epidemiological and Clinical Research, Veterans Affairs Medical Center, Minneapolis.
References
Prinssen M, Verhoeven ELG, Buth J, et al. A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms. N Engl J Med 2004;351:1607-1618.
Greenhalgh RM, Brown LC, Kwong GP, Powell JT, Thompson SG. Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial. Lancet 2004;364:843-848.
Hallett JW Jr, Marshall DM, Petterson TM, et al. Graft-related complications after abdominal aortic aneurysm repair: reassurance from a 36-year population-based experience. J Vasc Surg 1997;25:277-286.
Johnston KW, Canadian Society for Vascular Surgery Aneurysm Study Group. Nonruptured abdominal aortic aneurysm: six-year follow-up results from the multicenter prospective Canadian aneurysm study. J Vasc Surg 1994;20:163-170.
Lederle FA, Wilson SE, Johnson GR, et al. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 2002;346:1437-1444.
Collin J, Murie JA. Endovascular treatment of abdominal aortic aneurysms: a failed experiment. Br J Surg 2001;88:1281-1282.
Cronenwett JL, Seeger JM. Withdrawal of article by the FDA after objection from Medtronic. J Vasc Surg 2004;40:209-210.
Anderson PL, Arons RR, Moskowitz AJ, et al. A statewide experience with endovascular abdominal aortic aneurysm repair: rapid diffusion with excellent early results. J Vasc Surg 2004;39:10-19.
Lee WA, Carter JW, Upchurch G, Seeger JM, Huber TS. Perioperative outcomes after open and endovascular repair of intact abdominal aortic aneurysms in the United States during 2001. J Vasc Surg 2004;39:491-496.
Laheij RJ, Buth J, Harris PL, Moll FL, Stelter WJ, Verhoeven EL. Need for secondary interventions after endovascular repair of abdominal aortic aneurysms: intermediate-term follow-up results of a European collaborative registry (EUROSTAR). Br J Surg 2000;87:1666-1673.
Vallabhaneni SR, Harris PL. Lessons learnt from the EUROSTAR registry on endovascular repair of abdominal aortic aneurysm repair. Eur J Radiol 2001;39:34-41.
Beard JD, Thomas SM. Mid-term results of the RETA registry. Br J Surg 2002;89:520-520. abstract.
Carpenter JP, Baum RA, Barker CF, et al. Durability of benefits of endovascular versus conventional abdominal aortic aneurysm repair. J Vasc Surg 2002;35:222-228.
Peppelenbosch N, Buth J, Harris PL, van Marrewijk C, Fransen G. Diameter of abdominal aortic aneurysm and outcome of endovascular aneurysm repair: does size matter? A report from EUROSTAR. J Vasc Surg 2004;39:288-297.
Ouriel K, Srivastava SD, Sarac TP, et al. Disparate outcome after endovascular treatment of small versus large abdominal aortic aneurysm. J Vasc Surg 2003;37:1206-1212.
The United Kingdom Small Aneurysm Trial Participants. Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 2002;346:1445-1452.(Frank A. Lederle, M.D.)
Endovascular repair was developed to provide a less traumatic alternative. Endovascular grafts are positioned inside the aneurysm under radiologic guidance and secured with hooks or pressure to shield the segment containing the aneurysm from the blood pressure. The advent of endovascular repair has not been without controversy. After deciding to accept nonrandomized studies of effectiveness, the Food and Drug Administration (FDA) approved two graft systems in 1999, one of which was subsequently withdrawn, and has approved two more since then. Though endovascular repair has been extolled by many as the wave of the future, its brief but clamorous history has also been marked by FDA warnings and allegations of fraud, an editorial denouncing the procedure6 as a "failed experiment," and most recently, industry threats of legal action to block publication of an unfavorable FDA report.7
Nearly all studies have found that, as compared with open repair, endovascular repair results in reduced rates of operative morbidity, a shorter initial hospital stay, and shorter recovery time. Somewhat surprising, though, is that early studies found no improvement in operative mortality rates. That this has changed can be seen most dramatically in statewide data from New York over three years.8 In 2000, the rate of operative mortality for endovascular repair (3.1 percent) was similar to that for open repair (4.1 percent), but during the next two years, while the mortality rate associated with open repair remained unchanged, the rate for endovascular repair dropped to 1 percent. These rates were confirmed by a study of the 2001 Nationwide Inpatient Sample,9 which reported rates of operative mortality of 3.8 percent for open repair and 1.3 percent for endovascular repair.
Nevertheless, even large population-based observational studies can be biased by differences between treatment groups. Elective open repair is not offered to patients at high risk for operative complications, and endovascular repair is limited to patients who have a suitable segment of normal aorta below the renal arteries and who also have iliac arteries free of excessive plaque or tortuosity. Since the resulting differences between treatment groups could obviously affect outcomes, the reports from the two new randomized trials are welcome additions.
The DREAM trial investigators observed substantial reductions in the primary outcome of operative (30-day) morbidity and mortality with endovascular repair, as compared with open repair, that did not reach statistical significance owing to the relatively small sample size. The reduction in operative mortality with endovascular repair in the DREAM trial, from 4.6 percent to 1.2 percent, was very similar to the findings of the larger trial in the United Kingdom.2 That study, the Endovascular Aneurysm Repair (EVAR) trial, randomized 1082 patients and reported a significant reduction in operative mortality with endovascular versus open repair, from 4.7 percent to 1.7 percent. The remarkable agreement among the two population-based observational studies and the two trials leaves little doubt that endovascular repair is now associated with reduced rates of operative mortality and morbidity and a shorter initial hospital stay as compared with the rates for open repair.
Should we then accept the conclusion of the DREAM authors that "endovascular repair is preferable to open repair"? I believe we should not, because operative morbidity and mortality rates represent only half the equation; they address the risk associated with repair, but not the benefit. The more innocuous therapy is favored in a comparison of procedural complications, even if that therapy is ineffective. Just as we would not compare angioplasty and coronary bypass without considering subsequent cardiac events, we cannot compare open repair with endovascular repair without evaluating the long-term risk of aneurysm rupture and graft complications. There is reason to be cautious in this arena. Two large European registries have reported a failure rate for endovascular grafts of 3 percent per year (1 percent for rupture plus 2 percent for conversion to open repair), which is 10 times the failure rate of 0.3 percent for open repair, noted above, and a total secondary-intervention rate of 10 percent per year.10,11,12 Although potentially biased by substantial losses to follow-up, these registries are probably the best source available. The conclusion of the suppressed FDA report was that the total aneurysm-related mortality rate will probably be higher with endovascular repair than with open repair when late deaths are included.7
The late complications after endovascular repair have other important implications, such as the universal requirement for follow-up computed tomography each year for the rest of the patient's life — which is proving to be a considerable burden for both patients and physicians. Another may be the loss within one year of the initial advantage over open repair in the total number of days spent in the hospital.13 Recent reports from one of the registries14 and from the Cleveland Clinic15 raise yet another concern: long-term results after endovascular repair appear to be much worse for larger aneurysms, the ones most in need of repair. The four-year postoperative rupture rate in the registry study14 was 10 percent for abdominal aortic aneurysms measuring 6.5 cm or more in diameter at the time of endovascular repair, as compared with 2 percent for smaller aneurysms. Two years after endovascular repair in the Cleveland series, 6.1 percent of patients with abdominal aortic aneurysms that measured 5.5 cm or larger had aneurysm-related deaths, and 8.2 percent required conversion to open repair, as compared with 1.5 percent and 1.4 percent, respectively, of those with aneurysms measuring less than 5.5 cm.15
These findings are of particular concern because the aspect of the management of abdominal aortic aneurysms for which there is the most certainty, on the basis of results of two large trials,5,16 is the lack of benefit from repair of aneurysms smaller than 5.5 cm. Because the rupture rate of abdominal aortic aneurysms smaller than 5.5 cm that were followed with imaging surveillance was no more than 1 percent per year in those trials, it is unlikely that any treatment will be proved significantly better than surveillance for these patients. Nevertheless, the enthusiasm (aided by marketing and turf battles) surrounding endovascular repair has increased the temptation to repair smaller aneurysms. Forty-five percent of the registry patients and nearly 60 percent of the Cleveland patients who were treated with endovascular repair had aneurysms smaller than 5.5 cm.14,15
No comparison of treatments can be complete without consideration of cost. Despite the reduced rate of operative morbidity and the shorter hospital stay, numerous studies have found endovascular repair to be more expensive than open repair, primarily because of the high price of the grafts (about $13,000 per patient). The extra cost attributable to the use of endovascular repair in place of open repair in the United States in 2001 alone has been estimated at more than $50 million.9
The authors of the EVAR trial wisely advise us that the new findings should be considered "a license to continue scientific evaluation of , but not to change clinical practice" until evidence from trials is available for long-term outcomes.2 The EVAR trial should provide a first look at this evidence as early as next year, with more evidence to follow from the DREAM trial, the Veterans Affairs Open versus Endovascular Repair (OVER) trial, and the French Anévrisme de l'aorte abdominale: Chirurgie versus Endoprothèse (ACE) trial. Even if these trials show endovascular repair to be superior after several years of follow-up, the best treatment for younger patients will remain uncertain until we know how endovascular repair fares over decades. In addition, "small incision" and laparoscopic techniques have been developed, and further studies will be needed to clarify their roles.
Meanwhile, patient management should be guided by what we already know. Small aneurysms should be kept under surveillance with periodic ultrasonographic measurements — every two to three years for those smaller than 4.0 cm, and every six months for larger aneurysms. Elective repair should be considered for abdominal aortic aneurysms measuring 5.5 cm or larger. If the patient is a candidate for either open or endovascular repair, referral to a randomized trial is the best option.
Source Information
From the Center for Epidemiological and Clinical Research, Veterans Affairs Medical Center, Minneapolis.
References
Prinssen M, Verhoeven ELG, Buth J, et al. A randomized trial comparing conventional and endovascular repair of abdominal aortic aneurysms. N Engl J Med 2004;351:1607-1618.
Greenhalgh RM, Brown LC, Kwong GP, Powell JT, Thompson SG. Comparison of endovascular aneurysm repair with open repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled trial. Lancet 2004;364:843-848.
Hallett JW Jr, Marshall DM, Petterson TM, et al. Graft-related complications after abdominal aortic aneurysm repair: reassurance from a 36-year population-based experience. J Vasc Surg 1997;25:277-286.
Johnston KW, Canadian Society for Vascular Surgery Aneurysm Study Group. Nonruptured abdominal aortic aneurysm: six-year follow-up results from the multicenter prospective Canadian aneurysm study. J Vasc Surg 1994;20:163-170.
Lederle FA, Wilson SE, Johnson GR, et al. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 2002;346:1437-1444.
Collin J, Murie JA. Endovascular treatment of abdominal aortic aneurysms: a failed experiment. Br J Surg 2001;88:1281-1282.
Cronenwett JL, Seeger JM. Withdrawal of article by the FDA after objection from Medtronic. J Vasc Surg 2004;40:209-210.
Anderson PL, Arons RR, Moskowitz AJ, et al. A statewide experience with endovascular abdominal aortic aneurysm repair: rapid diffusion with excellent early results. J Vasc Surg 2004;39:10-19.
Lee WA, Carter JW, Upchurch G, Seeger JM, Huber TS. Perioperative outcomes after open and endovascular repair of intact abdominal aortic aneurysms in the United States during 2001. J Vasc Surg 2004;39:491-496.
Laheij RJ, Buth J, Harris PL, Moll FL, Stelter WJ, Verhoeven EL. Need for secondary interventions after endovascular repair of abdominal aortic aneurysms: intermediate-term follow-up results of a European collaborative registry (EUROSTAR). Br J Surg 2000;87:1666-1673.
Vallabhaneni SR, Harris PL. Lessons learnt from the EUROSTAR registry on endovascular repair of abdominal aortic aneurysm repair. Eur J Radiol 2001;39:34-41.
Beard JD, Thomas SM. Mid-term results of the RETA registry. Br J Surg 2002;89:520-520. abstract.
Carpenter JP, Baum RA, Barker CF, et al. Durability of benefits of endovascular versus conventional abdominal aortic aneurysm repair. J Vasc Surg 2002;35:222-228.
Peppelenbosch N, Buth J, Harris PL, van Marrewijk C, Fransen G. Diameter of abdominal aortic aneurysm and outcome of endovascular aneurysm repair: does size matter? A report from EUROSTAR. J Vasc Surg 2004;39:288-297.
Ouriel K, Srivastava SD, Sarac TP, et al. Disparate outcome after endovascular treatment of small versus large abdominal aortic aneurysm. J Vasc Surg 2003;37:1206-1212.
The United Kingdom Small Aneurysm Trial Participants. Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med 2002;346:1445-1452.(Frank A. Lederle, M.D.)