E D U C AT I O N A L S U P P L E M E N T

This educational supplement has been supported by an unrestricted educational grant from EndologixThis edition is an edited version of what appeared in the original supplement. Products not commercially available have been removed.

June 2017

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10 things to know about OvationBy Andrew Holden, Auckland, New Zealand

The Ovation iX Abdominal Stent Graft System is a 14F ultra-low profile stent graft. The uniquely

low profile of this device enables access to more patients than traditional endovascular aneurysm repair (EVAR) patients. Its conformable, kink-resistant PTFE iliac limbs are designed to reduce the risk of occlusion and staged deployment of the suprarenal stent allows precise placement. Uniquely, the polymer-filled sealing ring creates a custom seal and protects the aortic neck. Further, low permeability PTFE enables effective aneurysm exclusion and device patency.

Up until now, over 13,000 patients worldwide have been treated with the Ovation system, with over 1,300 patients treated in a controlled or real-world study. Clinical evidence at 30-day follow-up shows low major adverse event rates, short length of hospital stay, and low hospital admission rates, while five-year follow-up shows low rupture rate, no conversions, no migration and stable neck diameter.

Given this strong clinical track record, the question might be asked, “Why has Ovation had minimal adoption?” In my opinion, there may be some confusion between perception and reality. I have good experience using the device, and am able to pinpoint the 10 most

important things that I have learned about Ovation.

The neck remains importantWith traditional EVAR devices, the conventional neck requirement is a length ≥10mm or ≤15mm of parallel vessel along the length of the sealing zone. On the other hand, the Ovation system seals proximally at 13mm below the inferior renal (IR) artery, with neck diameter between 16mm and 30mm. With Ovation, the circumferential seal occurs at the midpoint of the sealing ring at IR+13.

Sizing with precisionSecond, although sizing with the Ovation system is more complex than for traditional EVAR, the results make it worthwhile when it comes to fixation and seal. For fixation, the operator must confirm that suprarenal aortic diameter at the level of the anchors (IR-35) does not exceed the maximum allowable diameter at that location for the chosen aortic body size. Similarly for seal, the operator should select aortic body size based on the diameter of the aorta at IR+13.

As for sizing the Ovation device in thrombus-laden or calcific necks, I would suggest that the operator includes 50% of thrombus (up to 2mm in any

direction), and also includes half the thickness of the calcium. As it relates to angulation and graft orientation, this should be determined by the suprarenal stent axis. The axis should be aligned with the expected stent axis, and if the angulation is between 45° and 60°, the axis should be adjusted by 10 degrees.

The integrated crossover lumenMy third piece of advice relates to the Ovation iX integrated crossover lumen. While contralateral limb cannulation could be difficult in the past, the crossover lumen helps to solve this problem.

Ovation iX Abdominal Stent Graft System

In this supplement:2 10 things to know about Ovation – by Andrew Holden4 Ovation: Finally an endograft that treats women equally – by Martin Storck

Endologix’s portfolio offers two innovative endograft systems that use polymer sealing to address some of the limitations of conventional endovascular aneurysm repair (EVAR). The Ovation iX Abdominal Stent Graft System, is an ultra-low profile endograft that enables access to more patients than traditional EVAR. The polymer-filled sealing ring creates a custom seal that stabilises the aortic neck, and the ultra-low profile enables treatment of patients with challenging distal anatomies. Not only has the Ovation platform demonstrated durability through five years in AAA patients, it can make EVAR a possibility for more women.* With Ovation iX, women may finally have gained equal access to EVAR. This supplement explores how personalising AAA with polymer sealing technologies is continuously changing the endovascular aortic landscape.

*Analysis based on available data from the LUCY Study female cohort (72 out of 76) and on comparisons with grafts ranging from 18F–21F OD manufactured by global market leaders.

Andrew Holden

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Wide applicabilityOf any other EVAR endograft on the market, the Ovation system has the widest applicability. This was indicated in the M2S Database of 43,000 abdominal aortic aneurysm computed tomography scans, in which 58% of Ovation patients can be treated within the instructions for use, compared to endografts manufactured by market leaders, which can treat 45–50% of patients.

Low rates of reinterventionThe fifth point relates to the reintervention rates associated with Ovation. Although Ovation’s neck is non-traditional and its sizing system is different, the need for reintervention, particularly for type Ia endoleaks, is extremely low. In the Ovation Global Pivotal Trial, for example, there was a 97% five-year freedom from reintervention for type Ia endoleak.

The benefits of low profileWhile other low-profile endografts may have shown otherwise, low-profile endografts can in fact be clinically effective and durable. The Ovation iX has the lowest profile (14F outer diameter) of any FDA-approved devices enabling access to more patients. Additionally, occlusions are rare, with a 99% five-year freedom from reintervention for occlusion.

Suitability for women and in smaller anatomiesGiven the ability to address patients with small access vessels, the Ovation platform is ideal for women with abdominal aortic aneurysms, as well as for patients with smaller anatomies such as those from an Asian descent who otherwise may not be suitable for traditional EVAR technology.

The backing of clinical evidenceThere are some who believe that the Ovation results are simply too good to be true, and discordant with current clinical experience. That was certainly my impression when first reviewing the data. However, the results associated with the device are backed by clinical evidence in over 1,300 patients in a number of trials. The five-year results from the Global Pivotal Clinical Study show good safety and effectiveness at five years and a low reintervention rate. Reinterventions for proximal endoleak were few (one year=two;

two years=one, three years=nil, four years=nil, five years=one). This results in a 97% five-year freedom from reintervention for type Ia endoleak and a 98% five-year freedom from aneurysm-related mortality.

In the US experience, the Ovation Global Pivotal Trial had the lowest reported major adverse event rate across the other IDE trials for FDA-approved abdominal aortic aneurysm devices.

Similarly, the Ovation EU Post-Market Registry has shown durable results through three years with 99% freedom from rupture, 99% freedom from conversion, 99% freedom from aneurysm-related mortality and 88% freedom from all-cause mortality. The EU registry also reports 97% freedom from type I endoleak, 99% freedom from type III endoleak, and in terms of freedom from three-year reintervention, 97% for type I endoleak, 95% for type II endoleak and 97% for occlusion.

Neck dilationAs for neck dilation, the ninth point on Ovation is that the sealing ring creates no chronic outward force and insulates the neck from systemic pressure and neck dilatation. In the core lab adjudicated Ovation Global Pivotal Trial, neck stability was noted through five-year follow-up with no evidence of aortic neck dilation. This is a unique and important finding and very different to the neck changes seen with EVAR devices using self-expanding stents. It confirms that once satisfactory neck seal is achieved, it remains durable in the long term.

Ovation Alto*: The next stepFinally, the next-generation product in the Ovation family— Ovation Alto—is an investigational device with a sealing ring at approximately IR+7mm, integrated balloon, webbing at the bifurcation to facilitate cannulation, offset aortic body legs for improved visualisation, and an ultra-low profile for small access and tortuous anatomy. Our first in-human experience with Alto has been very positive.

Ovation Alto is currently being evaluated in the ELEVATE IDE Study (Expanding patient applicability with polymer sealing Ovation Alto stent graft) with 75 patients at up to 15 centres, and the ELEVATE2 EU Post Market Registry is planned for 300 patients at up to 40 centres.

Ovation iX Abdominal Stent

Graft System

*The Ovation Alto Abdominal Stent Graft System has not been reviewed and/or approved in any market. Device not for sale.

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Ovation: Finally an endograft that treats women equallyBy Martin Storck, Karlsruhe, Germany

Abdominal aortic aneurysm (AAA) has historically been perceived as a man’s disease

even though women are also at risk —in fact, the rate is high with one in five AAA patients being women,1 and prevalence growing at a higher rate.2 Women with AAA tend to be older, and common risk factors such as smoking, heart disease, and chronic obstructive pulmonary disease should be consid-ered for AAA screening.1 Additionally, AAAs in women rupture at a smaller diameter than in men—three separate trials conducted in the USA, Canada, and Finland showed that a higher percentage of AAA in women than men rupture at a diameter of <5.5cm.3–5

Morphological eligibility for traditional endovascular aneurysm repair (EVAR) is an obstacle for operators to treat women with EVAR. Only 34% of women with AAA are eligible for EVAR treatment as compared to 54% in men.6,7 Even when treated with EVAR, women are more likely than men to sustain access-related arterial injury and have higher rates of iliac access angioplasty, uni-iliac conversion and iliac chimney conduit than men.8

In-hospital mortality is also greater for women after traditional EVAR.9 Statistics show that length of stay is longer for women than men, and that unplanned hospital readmissions at 30 days and one year are higher, as is mortality at 30 days and at one year post-EVAR.10,11 Late mortality is greater in women as well. A comparison of EVAR and open repair for elective and ruptured AAA found that the six-year survival rate for elective AAA is lower in women, although they sustained survival benefit over open repair, and that the six-year survival following ruptured AAA was substantially higher for men.12 Additionally, a meta-analysis of elective EVAR and open repair found that mortality favours men after both procedures.13

However, although the gender differ-ences are well documented, there were not prospective clinical trials dedicated to evaluating outcomes in women until the LUCY study that concluded in February 2017 in the USA. Women remain under-represented in EVAR clinical trials, with only about 10% of enrolled patients in EVAR investigational device exemption (IDE) studies being female. They are often precluded from EVAR because of their gender, and this ineligibility is driven by small access vessels and short neck length.7

Newer lower-profile devices on the market, which are better able to navigate the challenging distal anatomy, provide hope that women may finally have equal access to therapies that are more successful. The Ovation iX Abdominal Stent Graft System (Endologix) appears to address the issues that are specific to female patients with AAA. It has three main qualities that render it suitable: its broadened patient applicabil-ity, a custom polymer sealing ring and con-formable, kink-resistant limbs. It also has one of the lowest profile delivery systems, with a 14F delivery system outer diameter. The ultra-low profile system enhances deliverability and minimises vessel trauma, allowing fast, safe access to the aneurysm.

The conformable, kink-resistant iliac limbs facilitate the treatment of patients with narrow distal aortas. The polytetra-fluoroethylene (PTFE)-covered iliac limbs have helical architecture for exceptional flexibility and minimal luminal encroach-ment. The delivery catheter becomes more flexible as the diameter decreases. The Ovation system is built for manoeuvrabil-ity, which is critical in navigating through narrow and tortuous anatomies. The low permeability PTFE also allows effective aneurysm exclusion and device patency.

An important benefit of Ovation is the custom polymer sealing ring. Liquid polymer is injected to inflate the ring, and this then cures to a solid durable state. The seal is essentially customised for each patient. The sealing ring conforms to vessel wall irregularities and creates a circumferential seal at the mid-point of the sealing ring. Additionally, because the sealing ring technology exerts no chronic outward force and insulates the neck from blood pressure, the Ovation platform protects the neck.

The Ovation European Post-Market Registry14 is a multicentre prospective study of 501 patients across 30 European Union sites. Patients were enrolled between May 2011 and December 2013, with a Clinical Events Committee (CEC) adjudi-cation of device-related adverse events. A gender subanalysis shows that the 14% of females in the trial (there were 69 women and 432 men) had smaller access vessels and shorter, more angulated necks with larger diameters. Using Kaplan-Meier esti-mates by gender, data as of 6 October 2016 demonstrate that over a three-year period:n 100% of women had freedom from

AAA-related mortality, compared to 99% of men

Personalising AAA Care with Polymer Sealing

We must continue to strive against com-placency and the idea that AAA is not a female disease.

Unmet needs for women in EVARn 20% of all abdominal aortic

aneurysms present in women1

n Women rupture at smaller diameters3–5

n Aneurysm growth is higher in women2

n Women are underrepresented in EVAR trials7

n More women are precluded from EVAR7

n Smaller vessels and shorter necks drive EVAR ineligibility7

n Women are more prone to peri- and postoperative complications8

n In-hospital mortality is greater for women9

n Hospital stay is longer, readmissions more common and mortality greater in women10

n Both early and late mortality and morbidity are greater in women10,11

Martin Storck

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n 90% of women had freedom from all-cause mortality, compared to 87% of men

n 94% of women had freedom from type I endoleak, compared to 97% of men

n 100% of women had freedom from type III endoleak, compared to 99% of men

n 94% of women had freedom from occlusion, compared to 98% of men

n 100% of women had freedom from rupture, compared to 99.7% of men

n 99.5% of women had freedom from

conversion, compared to 98.5% of men, and

n 91% of women had freedom from AAA sac growth >5mm, compared to 93% of men.That women did as well as men in

this cohort is unusual and therefore represents a huge success.

Another study looking at the impact of Ovation on female patients is the LUCY study (Evaluation of Females who are Underrepresented Candidates for Abdominal Aortic Aneurysm Repair). This is the first prospective study to

prove non-inferiority in outcomes in female and male patients.

The LUCY study is a novel, prospec-tive study evaluating the clinical benefits associated with EVAR using the Ovation Prime and iX systems in female patients. The US prospective study consists of 225 patients, in a ratio of two males to every one female. Enrolment in 39 centres was completed on 14 February 2017, and results will be presented during the Vascular Annual Meeting of the SVS in June 2017. The EU LUCY Post-Market Registry is currently enrolling 60 patients in up to 12 EU centres, with a female single-arm.

Traditionally, women have had limited eligibility for EVAR and worse outcomes afterwards. But Ovation expands EVAR eligibility. The European Post-Market Registry demonstrates that women and men derive similar benefits with the Ovation stent graft through three years, and the LUCY study will further evaluate Ovation performance in females. My expectation is that it will increase the reach of EVAR to many more female patients than we have been able to treat previously, and to those with small and otherwise disadvantaged access femoral-iliac arteries.

We must continue to strive against complacency and the idea that AAA is not a female disease.

References 1. DeRubertis et al. J Vasc Surg 2007; 46: 630–5. 2. Solberg et al. Eur J Vasc Endovasc Surg 2005; 29:

145–9. 3. Skibba et al. J Vasc Surg 2015; 62(6): 1429–36. 4. Brown et al. J Vasc Surg 2003; 37: 280–4. 5. Heikkinen et al. J Vasc Surg 2002; 36: 291–6. 6. Ulug et al. Lancet 2017; 25 Apr: epub http://dx.doi.

org/10.1016/S0140-6736(17)30639-6 7. Sweet et al. J Vasc Surg 2011; 54(4): 931–7. 8. Lo et al. J Vasc Surg 2016; 63(3): 839–44. 9. Healthcare Cost and Utilization Project. Procedure

Code 39.71 Endo Impl Grft Abd Aorta. Retrieved 6 June, 2016 from http://www.hcup-us.ahrq.gov/

10. Hospital Episode Statistics (HES) of 20,780 EVAR cases performed between 2006–2015.

11. Deery et al. J Vasc Surg 2017; 65: 1006–1312. Egorova et al. J Vasc Surg 2011; 54: 1–12.13. Grootenboer et al. Br J Surg 2010; 97: 1169–79.14. Storck et al. J Cardiovasc Surg 2016; 21 Jun, epub

ahead of print.

Ovation platform is well suited for women with AAA

Men and women present different AAA morphologies

LUCY Registry first Karlsruhe case, January 2017

Ovation® AbdominalStent Graft System

www.endologix.com/herEVARstory #herEVARstory #LUCYstudy

* Non-significant difference1 Analysis based on available data from the LUCY Study female cohort (72 out of 76) and on

comparisons with grafts ranging from 18F – 21F OD manufactured by global market leaders.2 LUCY Study 30-day results extracted on May 1, 2017. N=225; Female arm n=76 & Male arm n=149.3 Deery, S, et al. J Vasc Surg 2017;65:1006-13.4 Broos, P, MD, et al. J Vasc Surg 2015;62:312-8.5 Ovation European Post-Market Registry 3-year results extracted on October 6, 2016. N=501;

Female n=69 & Male n=432.

Outcomes will vary and are not guaranteed. The Ovation® Abdominal Stent Graft Platform and associated components are not available in all countries or regions. Please contact your Endologix representative for details regarding product availability. Prior to use, refer to the “Instructions for Use” for complete and specific indications, contraindications, all warnings and precautions. Rx only. Endologix and Ovation are registered trademarks of Endologix, Inc. All other trademarks are the property of their respective owners. ©2017 Endologix, Inc. All rights reserved. MM1749 Rev 01

3Y E A R

Durability

Freedom from AAA-Related Mortality: Women 100% | Men 99% [ NS* ]

Freedom from Rupture: Women 100% | Men 99.7% [ NS* ]

Freedom from Reintervention for Type Ia Endoleak: Women 96% | Men 98% [ NS* ]

Freedom from Reintervention for Occlusion: Women 96% | Men 97% [ NS* ]

E U P O S T - M A R K E T R E G I S T R Y 5

Edna, LUCY Study Patient

OUR STORY

HER STORY IS

The first-ever prospective study to specifically evaluate EVAR in women

LUCY STUDY: The Ovation System can make EVAR a possibility for 28% - 109% more women with proven outcomes.1

100% deployment success occurred in women and 98.7% in men [ NS* ]

30D A Y

M A J O R C O M P L I C A T I O N S T Y P E I E N D O L E A K L I M B O C C L U S I O NM O R T A L I T Y

0%1.3% 1.3% 0%0% 2.0%0% 0%L U C Y S T U D Y 2

Traditional E V A R 5.8%3 1.3%4 2.0%49.6%31.1%32.9%3

Complications and Outcomes

[ NS* ]

[ p < .001 ] [ p < .001 ]

[ NS* ]

DISCOVER HOW WE ARE

REDEFINING WHAT’S

POSSIBLE FOR WOMEN:

VISIT OUR WEBSITE TO

LEARN THE RESULTS

OF THE LUCY STUDY,

THE FIRST-EVER

PROSPECTIVE STUDY

TO SPECIFICALLY

EVALUATE EVAR IN WOMEN.