December 17, 2003
In April 2001, we issued a public health notification on problems associated with endovascular grafts for repair of abdominal aortic aneurysm (AAA). This notification is to provide you with updated information on the mortality risks associated with the AneuRx® Stent Graft System when implanted for the prevention of AAA rupture, so that you can make a more informed decision about using this product to treat your patients. This information is based on an analysis of the extension of an investigational premarket study, which began in March of 1996, and involved a subgroup of 942 patients, followed through October 24th, 2002.
This Public Health Notification focuses on the AneuRx® device, as it is the only currently marketed device with long-term clinical follow-up. Two other commercially available stent graft systems are not included in this notice because appropriate long-term data are not currently available for these devices.
Our earlier notification identified several serious adverse events, including aneurysm ruptures, in patients treated with the AneuRx® Stent Graft. Since then, we have worked with the manufacturer, Medtronic AVE, as well as other sources, to obtain more complete follow-up data for the premarket cohort of patients who received the flexible model of the AneuRx® Stent Graft. These patients were considered good candidates for treatment with conventional open surgery. Certain categories of high risk patients were excluded from the study: American Society of Anesthesiology grade above IV; morbid obesity; acute renal failure or chronic dialysis; active systemic infection; less than one year of life expectancy; leaking aneurysm; aortic dissection; and aortic-iliac occlusive disease1.
Our analysis assessed aneurysm-related death rates in patients treated with the AneuRx® Stent Graft. We defined aneurysm-related death to include deaths from rupture of the AAA or from any procedure intended to treat the AAA. If a death occurred within one month of any procedure intended to treat the AAA, it was presumed to be aneurysm-related, unless there was evidence to the contrary.
The analysis showed that the perioperative (within 30 days) aneurysm-related death rate associated with the AneuRx® Stent Graft was 1.5% (14/942). Following implantation, an additional 8 AAA related deaths were identified during the subsequent 3 years of follow-up covering 2,080 patient years, for an annualized late mortality rate of 0.40% per year. This FDA analysis estimates an AAA-related death rate of 1.9% at one year post-implant, 2.2% at two years post-implant, and 2.7% at three years post-implant.
Analysis of perioperative mortality associated with both endovascular and open surgical repair is complex, and may vary as a function of the patient's age, comorbidities and aneurysm morphology, surgeon, and hospital. Adding to this complexity, studies of open surgical repair typically include patients from all risk levels, whereas the investigational premarket study excluded many high-risk categories. Published literature from multi-center studies including population-based series employing statewide and national databases, states that the mortality rates for open surgical repair range between 3-5% at 30 days2,3,4,5 This range is also consistent with the mortality for open surgery observed in two small aneurysm trials, the VA Cooperative Study6 and the UK Small Aneurysm Trial7, which reported operative mortality rates of 2.7% and 5.8%, respectively. Operative mortality rates reported in single center studies range between 0-5% 8,9,10,11,12,13,14. Results from multi-center studies may provide a better estimate of expected clinical outcome, as results from single center studies cannot typically be generalized to larger populations.
Repair of AAA also involves late mortality risk. This risk appears to be less for open surgery than for procedures using the AneuRx® stent graft. A review of late mortality associated with open surgical repair of AAA indicates the potential for mortality from pseudo-aneurysms developing at the aortic suture line and from infections15. Several individual studies suggest long term aneurysm-associated mortality rates associated with open surgical repair of AAA ranging from 0 % to 0.34 % per year, averaging approximately 0.18 % per year3,6,8,9,13,14,16,17. It should be noted that data from these studies have met varying standards of scientific rigor associated with different follow-up and diagnostic methodologies.
The results summarized above underscore the importance of following the manufacturer's instructions regarding careful selection and follow-up monitoring of patients with endovascular stent grafts, as stated in our April 2001 Public Health Notification.
Based on the findings of the present study, we recommend that the AneuRx® Stent Graft be used only in patients who meet the appropriate risk-benefit profile and who can be treated in accordance with the instructions for use.
In determining the risk-benefit profile for patients with AAA disease and the appropriate treatment option, among the factors to consider are:
- Long term AAA-related mortality, especially due to AAA rupture. The information above suggests that the risk of late AAA-related mortality associated with AneuRx® may exceed that associated with open surgery in some institutions. Because of this, the overall AAA-associated mortality from the AneuRx® Stent Graft is likely to cross-over and exceed the AAA-associated mortality from open surgery at some point in time.
- The experience of the institution or the physician. If open or endovascular surgery is performed in institutions or by physicians with little experience with open or endovascular AAA repair, the mortality rate may be considerably higher than average.
- Surgical risk factors for the individual patient. In patients who have substantial surgical risk factors such as age18 and comorbidities (e.g., cardiac, renal and pulmonary), the mortality rate for open resection of AAA may be considerably higher than average. For example, the predicted operative mortality for a 70-year old could range from 2% if no risk factors were present to over 40% if multiple co-morbidities were present19.
- The patient's life expectancy. Treatment with an endovascular graft may be preferable for patients with a shortened life expectancy.
- The patient's willingness to comply with the follow-up schedule for the endovascular graft.
Clinical updates of this investigational cohort are made available annually by Medtronic as a condition of AneuRx® approval. Practitioners can review the most recent information on the long term outcomes of AneuRx® patients enrolled in this investigation online, at www.Medtronic.com, and may request reprints from the Medtronic Customer Service Number, (800) 961-9055.
Reporting Adverse Events to FDA
The Safe Medical Devices Act (SMDA) of 1990 requires hospitals and other user facilities to report deaths and serious injuries associated with the use of medical devices, including endovascular stent grafts for AAA repair. You should follow the procedures established by your facility for such mandatory reporting.
We also encourage you to report any AAA stent graft malfunctions. You can report these directly to the device manufacturer. You can also report to MedWatch, the FDA's voluntary reporting program. You may submit reports to MedWatch one of four ways: online at http://www.accessdata.fda.gov/scripts/medwatch/ by telephone at 1-800-FDA-1088; by FAX at 1-800-FDA-0178; or by mail to MedWatch, Food and Drug Administration, HF-2, 5600 Fishers Lane, Rockville, MD 20857.
Future Public Health Notices will be provided as needed to update clinical information regarding the endovascular treatment of abdominal aortic aneurysm. The inputs from the above surveillance programs provide valuable resources for this purpose.
Getting More Information
FDA Medical Device Public Health Notifications are available on the Internet. You can also be notified through email each time a new Public Health Notification is added to our web page. To subscribe, visit: http://service.govdelivery.com/service/subscribe.html?code=USFDA_39.
David W. Feigal, Jr., MD, MPH
Center for Devices and Radiological Health
Food and Drug Administration
- Medtronic Corporation. Investigational Plan: Medtronic AneuRx
Endovascular Prosthesis Treatment of Abdominal Aortic Aneurysms.
- Anderson, et al. "A Statewide Experience with Endovascular AAA Repair –Rapid Diffusion with Excellent Early Results". Currently accepted for publication by the Journal of Vascular Surgery.
- Johnston KW, "Nonruptured Abdominal Aortic Aneurysm: Six-year Follow-up Results form the Multicenter Prospective Canadian Aneurysm Study", J Vasc Surgery 20: 163-70, 1994.
- Hallin A, et al, "Literature review of surgical management of abdominal aortic aneurysm", Eur J Vasc Endovasc Surg; 22:197-204, 2001.
- Dardik A, et al. "Results of elective abdominal aortic aneurysm repair in the 1990's: A population-based analysis of 2335 cases", JVS 30: 985-995, 1999
- Lederle FA, et al, "Immediate repair compared with surveillance of small abdominal aneurysms", N Eng J Med. 2002 May 9, 346(19):1437-44.
- Cronenwett JL, et al, "The United Kingdom Small Aneurysm Trial: Implications for surgical treatment of abdominal aortic aneurysms", J Vasc Surg 29(1); 191-194, 1999.
- Arko, et al, "Aneurysm-related death: Primary endpoint analysis for comparison of open and endovascular repair", J Vasc Surg 36(2): 297-304, 2002.
- Hallet, et al, "Graft-Related Complications after Abdominal Aortic Aneurysm Repair: Reassurance from a 36-Year Population-based Experience", J Vasc Surgery 25:277-286, 1997.
- Cao P, et al, "Abdominal Aortic Aneurysms: Current Management", Cardiologia 44(8): 711-717, 1999.
- Golden MA, et al, "Selective Evaluation and Management of Coronary Artery Disease in Patients Undergoing Repair of Abdominal Aortic Aneurysms", Ann. Surg 212(4): 415-423, 1990.
- Perry, et al, "Abdominal Aortic Aneurysm Surgery: The Basic Evaluation of Cardiac Risk", Ann. Surg 208(6): 738-742, 1988.
- Biancari F, et al, "Durability of Open Repair of Infrarenal Abdominal Aortic Aneurysm: A 15-Year Follow-up Study", J Vasc Surg 35: 87-93, 2002.
- Hertzer NR, et al, "Open Infrarenal Abdominal Aortic Aneurysm Repair: The Cleveland Clinic Experience from 1989 to 1998", J Vasc Surg 35,: 1145-1154, 2002.
- Limet R, Creemers E. Comparison Between Open and Closed Repair for Abdominal Aortic Aneurysms: A Word of Caution. Acta Chir Belg 100: 12-15, 2000.
- Plate G, Hollier LA, O'Brien P, Pairolero PC, Cherry KJ, Kazmier FJ. Recurrent Aneurysms and Late Vascular Complications Following Repair of Abdominal Aortic Aneurysms. Arch Surg 120: 590-594, 1985.
- Williamson WK, Nicoloff AD, Taylor LM, Moneta GL, Landry GJ, Porter JM. Functional Outcome after Open Repair of Abdominal Aortic Aneurysm. J Vasc Surg 33: 913-920, 2001.
- Sicard, GA, et al. "Endoluminal graft repair for abdominal aortic aneurysms in high risk patients and octogenarians. Is it better than open repair?" Ann. Surg. 234: 427-437, 2001.
- Steyerberg at al, "Perioperative mortality of elective abdominal aortic aneurysm surgery: A clinical prediction rule based on literature and individual patient data". Arch. Intern Med, 155: 1998-2004, 1995