Surgery Section - Endovascular Stent Grafts for Thoracic Aortic Aneurysms or Dissections

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

The traditional standard therapy for thoracic aortic aneurysm (TAA) is open operative repair with graft replacement of the diseased segment. This procedure requires lateral thoracotomy, use of cardiopulmonary bypass, long operation times, and may result in a variety of peri- and postoperative complications, with spinal cord ischemia considered the most devastating. Aortic dissection can be subdivided into Type A, which involves the aortic arch, and Type B, which is confined to the descending aorta. Type A dissections are usually treated surgically, while Type B dissections are usually treated medically, with surgery indicated for serious complications, such as visceral ischemia, impending rupture, intractable pain, or sudden reduction in aortic size. Dissections associated with obstruction and ischemia can also be subdivided into an obstruction caused by an intimal tear at branch vessel orifices, or by compression of the true lumen by the pressurized false lumen. It has been proposed that endovascular therapy can repair the latter group of dissections by redirecting flow into the true lumen.

The success of endovascular stent grafts of abdominal aortic aneurysms has created interest in applying the same technology to the aneurysms of the descending or thoracoabdominal aorta. In March 2005, the GORE-TAG Thoracic Endoprosthesis was approved by the U.S. Food and Drug Administration (FDA) for endovascular repair of aneurysms of the descending thoracic aorta. Use of this device requires that patients meet the following criteria:

1. Adequate iliac/femoral access
2. Aortic inner diameter in the range of 23-37mm
3. 2 cm or greater non-aneurysmal aorta proximal and distal to the aneurysm

Other devices are under development, and in some situations, physicians have adapted other commercially available stent grafts for use in the thoracic aorta.

Note: Endovascular stent grafts for abdominal aortic aneurysms are considered separately in Surgery Policy No. 98.

Policy/Criteria

Endovascular stent grafts may be considered medically necessary for the treatment of descending thoracic aortic aneurysms of 23-37mm of inner aortic diameter.*

Endovascular stent grafts are considered investigational for the treatment of thoracic aortic arch aneurysms or aortic dissections.

*Note that diameter specifications are for the inner aortic diameter (not the aneurysm diameter) and are based on the parameters identified for FDA approved use of the GORE TAG endoprosthesis.

Position Summary

Surgical Repair of Thoracic Aneurysms

The indications for the elective surgical repair of aortic aneurysms is based on estimates of the prognosis of the untreated aneurysm balanced against the morbidity and mortality of the intervention. The prognosis of TAA is typically reported in terms of the risk of rupture according to size and location, e.g., the ascending or descending or thoracoabdominal aorta. While several studies have estimated the risk of rupture of untreated aneurysms, these studies have excluded those patients who underwent surgical repair; therefore, the true natural history of thoracic aneurysms is unknown. Clouse and colleagues performed a population-based study of TAA diagnosed in Olmstead County, Minnesota, between the period of 1980 and 1994. (2) A total of 133 patients were identified; the primary clinical endpoints were cumulative rupture risk, rupture risk as a function of aneurysm size, and survival. The cumulative risk of rupture was 20 percent after 5 years. The 5-year risk of rupture as a function of aneurysm size at recognition was 0 percent for aneurysms less than 4 cm in diameter, 16 percent for those 4 to 5.9 cm, and 31 percent for aneurysms 6 cm or more. Interestingly, 79 percent of the ruptures occurred in women. Davies and colleagues reported on the yearly rupture or dissection rates in 721 patients with TAA. (3) A total of 304 patients were dissection free at presentation; their natural history was followed up for rupture, dissection, and death. Patients were excluded from analysis once operation occurred. Not surprisingly, the authors reported that aneurysm size had a profound impact on outcomes. For example, based on their modeling, a patient with an aneurysm exceeding 6 cm in diameter can expect a yearly rate of rupture or dissection of at least 6.9 percent and a death rate of 11.8 percent. In a previous report, the authors suggested surgical intervention of a descending aorta aneurysm if its diameter measured 6.5 cm. (4)

Surgical morbidity and mortality are typically subdivided into elective vs. emergency repair with a focus on the incidence and risk of spinal cord ischemia, considered one of the most devastating complications, resulting in paraparesis or paraplegia. The operative mortality of surgical repair of aneurysm of the descending and thoracoabdominal aorta is estimated at 6–12 percent and 10–15 percent, respectively, while mortality associated with emergent repair is considerably higher. (2,5) In elective cases, predictors of operative mortality include renal insufficiency, increasing age, symptomatic aneurysm, presence of dissection, and other comorbidities, such as cardiopulmonary or cerebrovascular disease. The risk of paraparesis or paraplegia is estimated at 3–15 percent. Thoracoabdominal aneurysms, larger aneurysms, presence of dissection, and diabetes are predictors of paraplegia. (6,7) A number of surgical adjuncts have been explored over the years to reduce the incidence of spinal cord ischemia, including distal aortic perfusion, cerebrospinal fluid drainage, hypothermia with circulatory arrest, and evoked potential monitoring. (8-11) However, the optimal protective strategy is still uncertain. (12)

This significant morbidity and mortality makes definitive patient selection criteria for repair of thoracic aneurysms difficult. Several authors have recommended an individual approach based on balancing the patients’ calculated risk of rupture with their anticipated risk of postoperative death or paraplegia.  However, in general, surgical repair is considered in patients with adequate physiologic reserve if the thoracic aneurysm measures from 5.5 to 6 cm in diameter, or in patients with smaller symptomatic aneurysms.

As noted above, Type A dissections (involving the ascending aorta) are treated surgically. There is more controversy regarding the optimal treatment of Type B dissections (i.e., limited to the descending aorta). In general, these dissections are managed medically unless serious complications arise, e.g., shock or visceral ischemia, although some surgeons recommend a more aggressive approach for younger patients in otherwise good health. However, although there is an estimated 50% one-year survival rate in those treated with an open surgical procedure, it is not clear whether that is any better or worse than those treated medically. (13) The advent of stent grafting, with the potential of reducing the morbidity and mortality of an open surgical procedure, may further expand the patients considered for surgical intervention.

Endovascular Stent Grafts

Currently open surgical resection of the aneurysm with graft replacement is considered the gold standard for aneurysm repair. Given the numerous patient factors (age, co-morbidities, location, and size of the aneurysm, presence or absence of dissection) and procedure variables involved in surgical repair, controlled trials of homogeneous patients and procedures would be required to determine if endovascular approaches are associated with equivalent or improved outcomes compared to surgical repair. Comparative mortality rates are of particular concern as well as the incidence of spinal cord ischemia. In addition, some patients who would not be considered a candidate for surgical therapy due to unacceptable risks might be considered candidates for an endovascular graft. In this situation, the outcomes of endovascular grafting could be compared to optimal medical management. In the abdominal aorta, the durability of the graft anchoring system and the incidence and long-term outcome of perivascular leaks around the graft have been concerns that are presumably shared by stent grafting in the thoracic aorta. Moreover, deployment of stent grafts into the thoracic aorta can be challenging; in some instances, reconstructions of the femoral or iliac artery may be required or open surgical access to the aorta or iliac artery is required. Also, left-subclavian-carotid transposition may be performed to facilitate an adequate proximal fixation site.

Similar to the FDA approval of abdominal aortic stent grafts, the FDA did not require randomized trials for approval of the GORE TAG thoracic endoprosthesis aortic stent graft. The FDA based its approval of the GORE TAG device on results of the PIVOTAL TAG 99-01 and the TAG 03-03 studies which are reported in the GORE TAG instructions for use manual. (14) TAG 99-01 was a controlled trial of patients with aneurysms of the descending thoracic aorta, treated with either surgical repair (n=94; 50 historical and 44 concurrent) or stent grafting (n=140) at 17 sites in the United States. Patients for both the graft group and control were selected using the same inclusion and exclusion criteria. After fractures in the wire frame of the TAG endoprosthesis were discovered in TAG 99-01, 51 patients underwent stent grafting with a modified TAG endoprosthesis at 11 sites in the subsequent TAG 03-03 study. (14) The primary outcomes assessed in both TAG 99-01 and TAG 03-03 were the number of patients who had one or more major adverse events and the number of patients that did not experience device-related events 12 months post-device deployment. The number of patients in the TAG 99-01 device group who experienced one or more adverse events was significantly lower than the surgical repair control group at one year follow-up (42% vs. 77% respectively, p<0.001). Major adverse events included neurologic, pulmonary, renal function and vascular complications, and major bleeding. In the TAG 99-01 device group, 4 of 140 patients (3%) experienced paraplegia or paraparesis vs. 13 of 94 patients (14%) in the control group. In the 12-month follow-up of TAG 99-01, 8 patients (3%) had one or more major adverse device-related events while the 12-24 month follow-up in this group noted only one major adverse device-related event. No major adverse device-related events occurred in the 30-day follow-up of the TAG 03-03 group. Information on 142 patients from the TAG 99-01 trial was published by Makaroun and colleagues; however, it did not report on comparative data from the surgical control group, citing regulatory requirements pending FDA review. (15) The authors reported favorable aneurysm-related (97%) and overall survival (75%) rates and concluded that the GORE TAG device was a safe alternative treatment for descending thoracic aortic aneurysms.

Makaroun reported 5-year results of endovascular treatment with the TAG device. (29) In this comparative study of 140 endograft patients with 96 non-contemporaneous controls, the authors concluded that endovascular treatment was superior to surgical repair at 5 years in anatomically suitable patients. For this study, significant sac size change was defined as 5 mm or greater increase or decrease from the 1-month baseline measurement. Migration was defined as 10 mm or more cranial or caudal movement of the device inside the aorta. At 5 years, aneurysm-related mortality was lower for TAG patients at 2.8% compared with open controls at 11.7% (P = .008). No differences in all-cause mortality were noted, with 68% of TAG patients and 67% of open controls surviving to 5 years. Endoleaks in the TAG group decreased from 8.1% at 1 month to 4.3% at 5 years. Five TAG patients have undergone major aneurysm-related re-interventions at 5 years (3.6%). Compared with the 1-month baseline, sac size at 60 months decreased in 50% and increased in 19% of TAG patients. At 5 years, there have been no ruptures, 1 migration, no collapse, and 20 instances of fracture in 19 patients, all before the revision of the TAG graft. They also noted that although sac enlargement was concerning, a modified device may be helping to resolve this issue.

While results from the FDA trials have not been published, a number of case series investigating endovascular repair of thoracic aortic aneurysms have been published, the results of which are consistent with the above FDA findings. The larger case series are reviewed below:

• In one of the largest case series of 103 patients with thoracic aneurysms, Mitchell reported 81 percent 1-year survival, with major perioperative morbidity occurring in 30 percent of patients. (16) Morbidities included paraplegia, cerebrovascular accident, and respiratory insufficiency. It should be noted that the stents used in this series were "homemade," using self-expanding Z stents covered by a woven Dacron tube graft.
• Cambria and colleagues also used a similar "homemade" device in their case series of 28 patients undergoing thoracic aortic stent graft repair. (17) A total of 50 percent of patients were not considered surgical candidates, and 32 percent of patients had urgent or ruptured conditions. The procedural mortality was 3.5 percent, with 3 additional deaths in the follow-up period of 17 months.
• Criado and colleagues studied 47 patients with either thoracic aneurysms or dissections who received a stent graft. (18) Two patients died within 60 days of follow-up and 8 patients had adverse events within the first 30 days. However, there were no instances of paraplegia, stroke, or surgical conversion.
• In a case series of 37 patients, Taylor and colleagues reported that no patient treated electively died and that 3 patients developed endoleaks, with 1 patient requiring conversion to an open procedure. (19)
• Ellozy and colleagues reported on the outcomes of 84 patients who underwent stent graft repair of descending aortic aneurysms. (20) All patients were participating in a series of FDA trials as part of an investigational device exemption (IDE). With a mean follow-up of 15 months, successful aneurysm exclusion was achieved in 82% of patients, while major complications (a mix of procedure and device related) occurred in 38%.
• Grabenwoger and colleagues reported on stent grafting of the descending aorta in 21 patients. (21) In 15 of the 21 patients, multiple stents were necessary for aneurysm exclusion. Two patients died postoperatively, and repeat stenting was done in 3 patients because of intraoperative leakage.
• Thompson and colleagues studied the outcomes associated with a stent called the Gore Excluder in a case series of 45 patients. (22) Two patients died in the immediate postoperative period, and 2 patients had endoleaks that necessitated a second procedure for successful repair. There were no cases of spinal ischemia.
• Najibi and colleagues also used the Gore Excluder and the Talent endoprosthesis in a case series of 19 patients. (23) This report is unique in that the results were compared to anatomically similar historic controls treated between 1996 and 1998. No patient in either group experienced spinal ischemia, and there was 1 perioperative death in each group. The incidence of procedure-related complications was similar in both groups. In the endovascular group the length of hospital stay was 6.2 days with no days in the intensive care unit compared to 16.3 days in the surgical group, with all patients requiring a period of intensive care.
• White and colleagues reported on the outcomes of 18 patients who were treated with a Medtronic stent graft as part of a phase I FDA- approved clinical trial. (24) With a follow up of 1 to 22 months, 24 percent of patients died, primarily due to co-morbid conditions. One patient suffered bilateral lower extremity paralysis. No endoleaks were detected during the follow-up period, and the aneurysms had either a stable or decreasing size.
• Finally, Gravereaux and colleagues reported on a case series of 53 patients undergoing endovascular stent grafting, with a specific focus on the risk of spinal cord ischemia. (25) Spinal cord ischemia developed in 5.7 percent of patients postoperatively.

Summary

In summary, with respect to endovascular treatment of descending thoracic aortic aneurysms, initial case series have reported promising results. When considered with the controlled trial of the GORE TAG endoprosthesis, the data are sufficient to demonstrate the use of endovascular stent grafts in the thoracic aorta are associated with equivalent or improved outcomes compared to open surgical repair.
In November 2003, Medtronic announced the initiation of the VALOR study (Evaluation of the Safety and Effectiveness of the Medtronic Vascular Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms). (26) The three-armed study will be conducted at 35 sites within the United States and will include the following subsets of patients:

• Patients with thoracic aortic aneurysms who are considered candidates for open surgical repair and who are of low to moderate risk of major complications;
• Patients in this group will also consist of open surgical candidates but will allow for enrollment of patients with Type B thoracic aortic dissections, aneurysms associated with dissections and pseudoaneurysms; and
• High-risk/non-surgical candidates, including patients with traumatic thoracic aortic aneurysms who do not have a complete severing of the aorta.

Medtronic has published the design of another ongoing trial on the Talent Thoracic Stent Graft, the INSTEAD trial (INvestigation of STEnt grafts in patients with type B Aortic Dissection) and announced plans to start the VIRTUE post-market patient registry to evaluate the treatment of acute, sub-acute and chronic descending thoracic aortic dissections (Type B).(27,28)  VIRTUE will enroll 100 patients at approximately 15-20 clinical centers in Europe, with a primary endpoint of disease, procedure or device related mortality at 12 months post-procedure.  In addition, enrollment has begun on a second VALOR study.  The VALOR II clinical trial will enroll a maximum of 125 patients at up to 30 investigational sites in the United States and will examine the safety and efficacy of Valiant in treating descending thoracic aortic aneurysms, or dangerous bulges in the descending thoracic aorta. (28)

Results of the European multicenter, randomized INSTEAD trial and the first VALOR trial were expected in 2006 but remain unpublished at the time of this review.

Summary

In summary, with respect to endovascular treatment of descending thoracic aortic aneurysms, initial case series have reported promising results.  When considered with the controlled trial of the GORE TAG endoprosthesis, the data are sufficient to demonstrate the use of endovascular stent grafts in the thoracic aorta are associated with equivalent or improved outcomes compared to open surgical repair.  The data related to endovascular stent grafts for the treatment of thoracic aortic dissections and aortic arch aneurysms is insufficient to permit conclusions regarding health outcomes.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 7.01.86
2. Clouse WD, Hallett JW, Schaff HV et al. Improved prognosis of thoracic aortic aneurysms: a population-based study. JAMA 1998;280(22):1926-9
3. Davies RR, Goldstein LJ, Coady MA et al. Yearly rupture or dissection rates for thoracic aortic aneurysms; simple prediction based on size. Ann Thorac Surg 2002;73(1):17-28
4. Coady MA, Rizzo JA, Hammond GL et al. Surgical intervention criteria for thoracic aortic aneurysms: a study of growth rates and complications. Ann Thorac Surg 1999;67(6):1922-6
5. Rectenwald JE, Huber TS, Martin TD et al. Functional outcome after thoracoabdominal aortic aneurysm repair. J Vasc Surg 2002;35(4):640-7
6. Huynh TT, Miller CC, Estrera AL et al. Thoracoabdominal and descending thoracic aortic aneurysm surgery in patients aged 79 years or older. J Vasc Surg 2002;36(3):469-75
7. Estrera AL, Miller CC, Huynh TT et al. Neurologic outcome after thoracic and thoracoabdominal aortic aneurysm repair. Ann Thorac Surg 2001;72(4):1225-31
8. Safi HJ, Miller CC, Subramaniam MH et al. Thoracic and thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass, profound hypothermia, and circulatory arrest via left side of the chest incision. J Vasc Surg 1998;28(4):591-8
9. Estrera AL, Rubenstein FS, Miller CC et al. Descending thoracic aortic aneurysm: surgical approach and treatment using the adjuncts cerebrospinal fluid drainage and distal aortic perfusion. Ann Thorac Surg 2001;72(2):481-6
10. Van Dongen EP, Schepens MA, Morshuis WJ et al. Thoracic and thoracoabdominal aortic aneurysm repair: use of evoked potential monitoring in 118 patients. J Vasc Surg 2001;34(6):1035-40
11. Safi HJ, Subramaniam MH, Miller CC et al. Progress in the management of type I thoracoabdominal and descending thoracic aortic aneurysms. Ann Vasc Surg 1999;13(5):457-62
12. Webb TH, Williams GM. Thoracoabdominal aneurysm repair. Cardiovasc Surg 1999;7(6):573-85
13. Umana JP, Miller DC, Mitchell RS. What is the best treatment for patients with acute type B aortic dissections – medical, surgical or endovascular stent grafting? Ann Thorac Surg 2002;74(5):S1840-3
14. Instructions for use: TAG thoracic endoprosthesis.  WL Gore & Associates.  2005.  www.goremedical.com/en/ifu/AJ0076.pdf  (Verified 08/01/08)
15. Makaroun MS, Dillavou ED, Kee ST et al. Endovascular treatment of thoracic aortic aneurysms: results of the phase II multicenter trial of the GORE TAG thoracic endoprosthesis. J Vasc Surg 2005;4(1):1-9
16. Mitchell RS, Miller DC, Dake MED et al. Thoracic aortic aneurysm repair with an endovascular stent graft: the "first generation." Ann Thorac Surg 1999;67(6):1971-80
17. Cambria RP, Brewster DC, Lauterbach SR et al. Evolving experience with thoracic aortic stent graft repair. J Vasc Surg 2002;35(6):1129-36
18. Criado FJ, Clark NS, Barnatan MF. Stent graft repair in the aortic arch and descending thoracic aorta: a 4-year experience. J Vasc Surg 2002;36(6):1121-8
19. Taylor PR, Gaines PA, McGuinness CL et al. Thoracic aortic stent grafts – early experience from two centres using commercially available devices. Eur J Vasc Endovasc Surg 2001;22(1):70-6
20. Ellozy SH, Carroccio A, Minor M et al. Challenges of endovascular tube graft repair of thoracic aortic aneurysm: midterm follow-up and lessons learned. J Vasc Surg 2003;38(4):676-83
21. Grabenwoger M, Hutschala D, Ehrlich MP et al. Thoracic aortic aneurysms: treatment with endovascular self-expandable stent grafts. Ann Thorac Surg 2000;69(2):441-5
22. Thompson CS, Gaxotte VD, Rodriguez JA et al. Endoluminal stent grafting of the thoracic aorta: initial experience with the Gore Excluder. J Vasc Surg 2002;35(6):1163-70
23. Najibi S, Terramani TT, Weiss VJ et al. Endoluminal versus open treatment of descending thoracic aortic aneurysms. J Vasc Surg 2002;36(4):732-7
24. White RA, Donayre CE, Walot I et al. Endovascular exclusion of descending thoracic aneurysms and chronic dissections: initial clinical results with the AneuRx device. J Vasc Surg 2001;33(5):927-34
25. Gravereaux EC, Faries PL, Burks JA et al. Risk of spinal cord ischemia after endograft repair of thoracic aortic aneurysms. J Vasc Surg 2001;34(6):997-1003
26. www.medtronic.com/newsroom/news_20031110a.html (Verified 08/01/08)
27. Nienaber CA, Zannetti S, Barbieri B et al. INvestigation of STEnt grafts in patients with type B Aortic Dissection: design of the INSTEAD trial--a prospective, multicenter, European randomized trial. Am Heart J 2005; 149(4):592-9
28. Medtronic Announces Start of Two Clinical Trials Studying Treatment of Thoracic Aortic Aneurysms and Dissections: INSTEAD, VIRTUE, VALOR I and II. http://www.clinicaltrials.gov/ct2/results?term=thoracic+aortic+aneurysm (Verified  08/01/08)
29. Makaroun MS, Dillavou ED, Wheatley GH et al. Five-year results of endovascular treatment with the Gore TAG device compared with open repair of thoracic aortic aneurysms. J Vasc Surg 2008 Mar 17 (Epub ahead of print)

Cross References

Endovascular Grafts for Abdominal Aortic Aneurysms, Regence Medical Policy Manual, Surgery, Policy No. 98

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