EVAR 2012: Indications, Devices, and Techniques

Abdominal aortic aneurysms (AAA) are an important form of cardiovascular disease. In the U.S. alone, more than 1 million individuals between the ages of 50 and 84 may harbor an AAA.¹ One hundred thousand new cases are diagnosed and 50,000+ patients undergo AAA repair each year (Figure 1). As many as 15,000 deaths per year can be attributed to this disease, mostly related to rupture,^1,2 which makes it the 13th leading cause of mortality overall. Men are affected far more frequently than females (5:1), but women are well documented to have worse outcomes after repair and higher rupture mortality.^3,4 Since the 1950s when surgical techniques for resection and graft replacement were developed, definitive treatment has been available. AAA repair became a relatively common operation as early as the 1960s, and evolved to be one of the signature procedures for vascular surgeons everywhere. Amid the good news nature of such developments, it emerged rapidly that the operation was maximally invasive and often caused major morbidity, even death. Worse yet, many patients were excluded from treatment when deemed medically unfit for such major surgery.

Emergence of EVAR

Dr. Juan Parodi, together with Drs. Julio Palmaz and Hector Barone, performed the first endovascular aneurysm repair (EVAR) procedure at the Instituto Cardiovascular de Buenos Aires (Argentina) on Sept 7, 1990.Although unknown at the time, they eventually learned that others had been developing similar less invasive solutions for AAA disease, most notably Volodos in the Ukraine,⁶ Lazarus in the U.S.,⁷ and a few others.⁸ The revolutionary new technique was destined to change everything and signaled the beginning of a whole new era in aortic surgery and vascular surgery overall.⁵

EVAR Devices, Then and Now

Evolving over the last 20 years, FDA approval of the first two stent-graft devices at the end of September 1999 (Medtronic’s AneuRx and Guidant’s Ancure) marked the end of the infancy phase of the emerging new technologies. Major improvements and new iterations were just around the corner. The next logical step was major design improvements and enhanced devices. In all, 7 FDA-approved EVAR endograft devices are currently available in the U.S. market (Figure 2).

The latest unlimited approval was Medtronic’s Endurant in December 2010. It is thought of as an advanced-generation technology⁹ and has become quite dominant in many markets worldwide, the U.S. included. More recently yet, TriVascular’s Ovation AAA stent graft received limited Humanitarian Device Exemption (HDE) approval, predicated on its ultra-low profile 14 Fr delivery system that enables treatment of patients with very small and/or diseased access femoral and iliac arteries (Figure 3). It is a promising new technology and outcomes have been favorable so far, but a much larger clinical experience and long-term data will be required before rendering definitive judgment on the Ovation stent graft device.Just recently in April 2012, the FDA approved the premarket approval application for the Zenith Fenestrated AAA stent graft by Cook (Figure 4). This device features fenestrations and/or scallops to allow grafting into and revascularization of the renal and visceral arteries. Each proximal body component is customized for an individual patient. Commercial launch is expected in the summer of 2012.

Device Families

Stent grafts are frequently categorized as first generation, second generation, etc. It is a confusing nomenclature because generations have never officially been defined. It may prove more useful to describe devices according to their origin, or families. EVAR device families can therefore be defined by their manufacturers (Figure 5):

• Aptus: Endostaple, FDA-approved but not the graft;
• Bolton: Treovance, not approved;
• Cook: Zenith; Zenith Flex, FDA-approved; Zenith LP, not approved; and now Zenith Fenestrated, FDA-approved - customized;
• Cordis: Incraft, not approved;
• Endologix: Powerlink, FDA-approved; Nellix, not approved;
• Gore: Excluder; Excluder C3, FDA-approved;
• Lombard: Aorfix, not approved;
• Medtronic: AneuRx; Talent; Endurant, all FDA-approved;
• Trivascular: Ovation, HDE FDA approved;
• Vascutek: Anaconda, not approved.

Current and Future Developments

While the currently available devices perform quite well in general, there are still several unmet needs that have appropriately become the main drivers for ongoing research and new developments, including:

• AAA with a short and/or angulated proximal neck. Endurant was the first commercial U.S. device developed with such anatomies in mind. However, the approved on-label indication does not reflect such capabilities, and although favorable early and mid-term European results with the use of Endurant in such disadvantaged necks have been reported, the potential for failure and complications in such settings remains incompletely studied at this time.⁹ Another advanced design technology for the specific purpose of treating severely angulated aortic necks is the AorFix stent graft (Figure 8), which was granted CE mark regulatory approval for commercialization in Europe with an on-label indication that includes AAA anatomies with a proximal neck angulation up to 90°. This is the first and only regulatory approval (anywhere in the world) for angulations of such severity.
• Lower profile. Lowering stent-graft profile remains an important objective to obviate lingering access-related issues, improve deliverability, and enable the shift to percutaneous EVAR. It is likely that several stent grafts with an outer diameter profile of 14-16 Fr will become available within the next few years. The recent HDE approval of the Ovation device is encouraging in this regard.
• Branches. Aortic branch management represents the next frontier with the promise to expand applicability and optimize performance.  Cook’s Fenestrated AAA device was just approved and is expected to be launched in the U.S. in the near future.¹⁰ While this must be viewed as a significant development, the focus will likely shift to non-customized, simpler, and less expensive platforms that can be used off the shelf for many such patients in the future.¹¹ Endologix’s Ventana fenestrated-cuff design is an excellent example of the current and future trends in this area.¹²
• Treat the sac. The Endologix Nellix device represents the first serious attempt at thinking outside the box in the EVAR field.¹³ The Nellix system aims to treat the sac and does not rely on proximal-neck fixation and seal with subsequent aneurysm-sac exclusion/depressurization followed by sac shrinkage. With this system, the aneurysm itself is anchored with a set of 2 thin-walled polyester polymer-filled endobags that freeze the sac in a definitive and permanent manner (Figure 6). So far, clinical experience is limited (n=34 patients in an international phase I trial), but device performance and clinical outcomes show promising results. Regulatory approval in Europe is expected later this year. While it is too early to make predictions, the Nellix device could potentially revolutionize EVAR therapy by potentially eliminating type II endoleaks and being applicable to no-neck aneurysms.

Evidence-Based Treatment of AAA

Modern treatment of AAA is increasingly being performed based on scientific evidence. The EVAR-1 and DREAM trials^14,15 have contributed the most in this regard. The most powerful data point related to operative (30-day) mortality: 5% for OR vs 1.5% for EVAR, a 3.5-fold difference in favor of endovascular treatment. The mortality advantage held out for 4 years, but there was no difference in all-cause mortality. Long-term complications and secondary interventions favored OR over EVAR. A recent publication of the EVAR-1 trial results with follow-up extended up to 10 years (median 6 years)¹⁶ showed that the AAA-related mortality benefit had been lost by the conclusion of the study. A number of late aneurysm ruptures and new complications appeared up to 8 years post-procedure with 30% of the patients requiring a secondary intervention (up to 8 years); the same was seen in the DREAM trial (up to 6 years).

While the EVAR-1 and DREAM trials show favorable results for EVAR, the emerging overall picture is somewhat mixed because of the late failures, including late aneurysm ruptures and the relatively high rate of reinterventions. It is paramount to note that these trials were designed and patient enrollment completed more than 10 years ago, with many substantial improvements and technological evolutions having occurred since then. Therefore, it would not be far-fetched to assume that endovascular experts today could achieve far better outcomes than those produced 10 years ago. Tempering such enthusiasm is recent information on long-term follow-up revealing unexpected high rates of sac enlargement and other issues.¹⁷ Experts and researchers worldwide are still hard at work elucidating the relevance of such findings.

EVAR: Transforming the AAA Therapy Landscape

EVAR developments have had enormous impact in AAA treatment. Though the total number of AAA repairs hasn’t changed much if at all, EVAR noticeably affected the comparative dominance of one procedure over the other and the procedures’ outcomes.¹⁸ Elective aneurysm repairs have increased by 8% and repair of ruptured aneurysms (rAAA) has plummeted by 35% since the introduction of EVAR in the U.S. in 1999. By 2004, EVAR overtook OR as the most common treatment in the U.S. and by 2005, EVAR accounted for 56% of all intact aneurysm repairs but only 27% of operative mortality, which is a life-saving achievement. Since 1993, AAA-related deaths decreased by 42%, and for every constituent of this drop (including total repair-related deaths, rAAA repair deaths, and elective repair deaths), the decline rate in mortality has proven significantly steeper after the introduction of EVAR. However, OR mortality remained stable with an average of 4.6%. This can be contrasted with an EVAR mortality of 1.3%. Most significantly, recent evidence shows that long-term survival may be better after EVAR when compared with open surgical treatment.¹⁹

In closing, the EVAR 2012 landscape is populated with an exciting mix of impressive achievements, many lives saved, fast-moving technologies, and new treatment paradigms. EVAR’s future potential is essentially unlimited, but the lingering unresolved issues noted above do need to be overcome before we can proclaim a total triumph.
 

References

1. Kent KC, Zwolak RM, Egorova NN, et al. Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. J Vasc Surg. 2010;52(3):539-548.
2. Schermerhorn M. A 66-year-old man with an abdominal aortic aneurysm: review of screening and treatment. JAMA. 2009;302(18):2015-2022.
3. Norman PE, Powell JT. Abdominal aortic aneurysm: the prognosis in women is worse than in men. Circulation. 2007;115(22):2865-2869.
4. Vouyouka AG, Kent KC. Arterial vascular disease in women. J Vasc Surg. 2007;46(6):1295-1302.
5. Criado FJ. EVAR at 20: the unfolding of a revolutionary new technique that changed everything. J Endovasc Ther. 2010;17(6):789-796.
6. Volodos NL, Shekhanin VE, Karpovich IP, Troian VI, Gur’ev IuA. A self-fixing synthetic blood vessel endoprosthesis [in Russian]. Vestn Khir Im I I Grek. 1986;137(11):123-125.
7. Lazarus HM. Intraluminal graft device, system and method. United States Patent number 4,787,899; November 29 1988 (filed December 10, 1986).
8. Balko A, Piasecki GJ, Shah DM, Carney WI, Hopkins RW, Jackson BT. Transluminal placement of intraluminal polyurethane prosthesis for abdominal aortic aneurysm. J Surg Res. 1986;40(4):305-309.
9. Bastos Gonçalves F, de Vries JPPM, van Keulen JW, et al. Severe proximal aneurysm neck angulation: early results using the Endurant stentgraft system. Eur J Vasc Endovasc. 2011;41(2):193-200.
10. Verhoeven EL, Vourliotakis G, Bos WT, et al. Fenestrated stent grafting for short-necked and juxtarenal abdominal aortic aneurysm: an 8-year single-centre experience. Eur J Vasc Endovasc Surg. 2010;39(5):529-536.
11. Park KH, Hiramoto JS, Reilly LM, Sweet M, Chuter TA. Variation in the shape and length of the branches of a thoracoabdominal aortic stent graft: implications for the role of standard off-the-shelf components. J Vasc Surg. 2010;51(3):572-576.
12. Endologix Announces First Clinical Implant of Ventana™ Stent. 2011. https://www.prnewswire.com/news-releases/endologix-announces-first-clinical-implant-of-ventana-stent-graft-106514633.html
13. Donayre CE, Zarins CK, Krievins DK, et al. Initial clinical experience with a sac-anchoring endoprosthesis for aortic aneurysm repair. J Vasc Surg. 2011;53(3):574-582.
14. EVAR Trial Participants. Endovascular aneurysm repair versus open repair in patients with abdominal aortic aneurysm (EVAR trial 1): randomised controlled trial. Lancet. 2005;365(9478):2179-2186.
15. Blankensteijn JD, de Jong SECA, Prinssen M, et al; for the Dutch Randomized Endovascular Aneurysm Management (DREAM) Trial Group. Two-year outcomes after conventional or endovascular repair of abdominal aortic aneurysms. N Engl J Med. 2005;352(23):2398-2405.
16. The United Kingdom EVAR Trial Investigators, Greenhalgh RM, Brown LC, Powell JT, Thompson SG, Epstein D, Sculpher MJ. Endovascular versus open repair of abdominal aortic aneurysm. N Engl J Med. 2010;362(20):1863-1871.
17. Schanzer A, Greenberg RK, Hevelone N, et al. Predictors of abdominal aortic aneurysm sac enlargement after endovascular repair. Circulation. 2011;123(24):2848-2855.
18. Giles KA, Pomposelli F, Hamdan A, Wyers M, Jhaveri A, Schermerhorn ML. Decrease in total aneurysm-related deaths in the era of endovascular aneurysm repair. J Vasc Surg. 2009;49(3):543-551.
19. Jackson RS, Chang DC, Freischlag JA. Comparison of long-term survival after open vs endovascular repair of intact abdominal aortic aneurysm among Medicare beneficiaries. JAMA. 2012;307(15):1621-1628.

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From the MedStar Union Memorial Hospital, Baltimore, Maryland.

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The author reports honoraria received for consultancy from Medtronic.