VDM Speaks with Jes S. Lindholt, MD, DMSci, PhD, Principal Investigator, Scandinavian PROPATEN Clinical Trial

Tell us about the findings of the Scandinavian clinical trial involving the GORE^® PROPATEN^® heparin-bonded vascular graft for the treatment of lower-limb ischemia.

Overall, the heparin-bonded vascular expanded polytetrafluoroethylene (ePTFE, GORE^® PROPATEN^® Vascular Graft, W. L. Gore & Associates, Inc., Flagstaff, Arizona) graft had significantly better primary and secondary 1-year patency rates compared to ordinary (ePFTE grafts) without heparin bonding. This benefit was especially observed in patients with critical ischemia and in those needing a femoro-popliteal bypass. In such cases, the risk of losing primary patency was reduced by half with the use of the PROPATEN vascular graft.

Tell us about the study’s design and scope. What were the inclusion and exclusion criteria and primary and secondary endpoints?

The aim of this study was to compare the 1-year primary patency of the PROPATEN with pure ePTFE in a robust, randomized, blinded, clinically controlled, multi-center study. Primary and secondary patency rates were the primary and secondary endpoints, and inclusion criteria involved patients who were scheduled to undergo a femoro-femoral bypass or a femoro-popliteal bypass due to chronic lower limb ischemia. Consequently, claudicants, as well as patients with critical ischemia, were included, but those with acute ischemia were not. The only real exclusion criteria was if proper follow up could not be expected, as allergy to heparin is extremely rare. Eleven Scandinavian centers participated, and the investigators agreed to conduct the trial with a substantial power of 90% to minimize the risk of failing to detect a relevant difference in patency. Thus, we calculated that a minimum of 484 patients were needed, but ended up randomizing a total of 569 patients. Of those who underwent the scheduled procedure, 546 had sufficient follow-up data for the assessment of 1-year primary patency.

What type of imaging technology was used to determine procedural outcomes?

If occlusion was suspected, it had to be confirmed by duplex scan or some kind of arteriogram. When an occlusion was not suspected, a mandatory duplex scan after 1 year was performed.

How long will the patients be followed?

Due to the fact that the trial is an independent and unfunded project, only 1-year follow up was initially planned because this is what is normally offered at the participating centers. However, after the enrollment success and the initial results, the department managers involved have agreed to an additional 2-year follow-up examination.

Are patients with critical limb ischemia candidates for the GORE PROPATEN Vascular Graft?

Definitely. It seems that the more difficult the clinical situation becomes, the better it performs compared to pure ePTFE grafts. In general, the GORE PROPATEN Vascular Graft reduces the risk of primary patency loss by half in critical ischemia, by 40% when a femoro-femoral crossover bypass is needed, and by two-thirds when a femoro-popliteal bypass is needed.

Describe the features of the PROPATEN vascular graft. What makes it unique?

It is not the first time that heparin-bonded grafts have proven to be beneficial. Devine and McCullum showed this in a beautiful multicenter randomized, controlled trial from the south of Manchester. However, these results did not change our clinical habits — at least not in Scandinavia, probably because the heparin-bonded grafts were made of Dacron. I think there is a preference for ePTFE grafts due to the material’s physical features compared to Dacron — and this is perhaps combined with tradition. As a young trainee you use what is available in your department and tend to stick with these products and devices when you become more experienced and independent. In my view, the PROPATEN graft does not have unique physical features compared to other ePTFE grafts; what makes it unique is that it is the only heparin-bonded ePTFE graft that has been shown to improve patency rates, and is thus an ePTFE alternative to heparin-bonded Dacron grafts.

What do you see in the future for the treatment of lower limb and critical limb ischemia?

The expansion of endovascular approaches to treat longer and longer lesions will continue. However, it is difficult for me to believe that it is as efficient as bypassing long lesions. Unfortunately, this development will be without justification from high level-of-evidence trials similar to the Scandinavian PROPATEN Trial. If, as I expect, such trials are performed and show surgical bypass to be superior, the enthusiasm for endovascular treatment will continue, with the argument that techniques and adjuvant therapies have developed and improved since the trials started.

Disclosure. Dr. Lindholt discloses that he has received financial support from W. L. Gore & Associates to arrange the annual meeting of investigators, as well as funding to participate in the Veith and CX symposia.

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Jes S. Lindholt, MD, PhD, DMSci., Consultant Vascular Surgeon, Department of Vascular Surgery, Viborg Hospital, Viborg, Denmark. Since 2004, Jes Lindholt has been the head of the Vascular Research Unit at Viborg Hospital, and an associate professor affiliated with the University of Aarhus. His primary research focus involves abdominal aortic aneurysms (AAA): epidemiology, prevention, screening, biomarkers, and medical treatment of aneurysms. In 1998, he defended a PhD thesis on the initial results of screening for AAA, and in 2010, he became doctor of medical sciences (DMSci) with a thesis on AAA. The “Scandinavian PROPATE® Trial” is his first trial as principal investigator for the treatment of lower limb ischemia. This trial was initiated because the hospital would not spend money on a more expensive graft that had not been proven superior. He has published more than 120 scientific papers indexed in PubMed, and is a member of the European Research Consortium: Fighting Aneurysmal Disease (FAD).