In general, patients suffering from an abdominal aortic aneurysm (AAA) currently have two treatment options: open surgery, which involves a large incision in the abdomen to allow a surgeon to clamp off the aorta and replace the damaged section with a surgical graft; or, a much less invasive alternative, endovascular aortic repair (EVAR), during which an endograft is guided into the body by a catheter system to seal off the aneurysm from within.

It's not hard to figure out which method most physicians and patients would prefer – EVAR usually results in a shorter recovery period and has a higher patient survival rate than open surgery, according to Cook Medical (Bloomington, Indiana). But a significant population of AAA patients, particularly women and Asians, are not currently good candidates for EVAR. Cook is hoping to change that with its next-generation Zenith Low Profile AAA (Zenith AAA LP) endovascular graft.

The company reported this week that it has initiated enrollment in a trial of its Zenith AAA LP endograft. The device is aimed at enhancing safety for patients undergoing endovascular aneurysm repair of AAAs, while also making the procedure available to patients whose vascular anatomies are unsuited to the large-diameter device in use today, Cook said.

"There is a certain number of patients that the current devices on the market don't really work well for," Mark Farber, MD, associate professor of surgery and program director of the vascular surgery fellowship at the University of North Carolina Hospitals (Chapel Hill), told Medical Device Daily. Farber said the vascular anatomies in about 5% to 10% of AAA patients are small and the catheter through which the device is delivered won't fit. When that happens, the physician has to move to an artery farther up in the belly that is larger, he said.

By reducing the diameter of the delivery system to 16 French and eliminating the need for a top cap to ensure precise delivery of the device to the target location within the patient's aorta, Cook said the Zenith AAA LP represents a significant reinvention of its Zenith Flex AAA endograft system. If proven safe and effective, the new system could make EVAR possible for millions of AAA sufferers worldwide, particularly female and Asian patients who tend to have narrower, more tortuous vessels that current AAA endografts may have difficulty navigating safely, the company said.

Cook reported getting an investigational device exemption conditional approval to begin this 120-patient trial last fall (Medical Device Daily, Nov. 24, 2008).

Farber performed the first placement in a U.S. patient of Cook's Zenith AAA LP endograft. He told MDD that the procedure was performed several weeks ago and that the patient has already been back for a follow-up appointment and the device is in "great position" and is working as anticipated.

"While EVAR has become the preferred treatment method for AAA in most cases, patients with smaller vascular anatomies had few, if any, treatment options outside of highly invasive open surgery," Farber said. "With the new Zenith Low Profile AAA endovascular graft, physicians can now provide this challenging patient population with the solution of choice for treating AAA, which is the 13th leading cause of death in the U.S. The Zenith LP AAA endovascular graft provides a low-profile delivery system and a simplified deployment procedure while maintaining the precision of the current Zenith Flex endograft. The Zenith LP creates more options for my patients that in the past could not have the endovascular procedure. The LP is building upon the tradition of technology innovation within the Zenith product line."

Mike Williams, product manager for the AAA line at Cook, told MDD that physicians have told the company they get the precision of deployment that other grafts have lacked but the device is also easy to deliver. "With this one they get that accuracy and it's a very simple deployment so that's probably the biggest change that people will notice," he said.

Williams said Cook hopes to complete the trial by the end of the year and seek a CE mark for it early next year, followed by FDA approval.

AAAs affect nearly 200,000 Americans every year and occur when a section of the aortic wall, the body's main blood vessel, weakens and creates a dangerous bulge that can rupture. When treated by open surgery, a large incision is made in the abdomen to allow a surgeon to clamp off the aorta and replace the damaged section with a surgical graft. This highly invasive method can lead to serious complications and extended recovery times. Conversely, during the minimally invasive EVAR procedure, an endograft is guided into the body by a catheter system to seal off the aneurysm from within. This treatment method usually results in a shorter recovery period and has a higher patient survival rate than open surgery, according to Cook.

In addition to having a low profile, Farber said the device is also is a nitinol-based product unlike previous stainless steel versions of the device. He said the stainless steel devices were a problem for some patients who had to have an MR scan and the metal hindered the imaging.

"[The Zenith AAA LP] still has incorporated the other changes that we've made to the device over time ... few modifications so we can treat more patients effectively," Farber said.

Significantly smaller than most commonly used systems measuring 20 French to 24 French, the Zenith AAA LP system features a 16 French delivery sheath. Its size and simple delivery mechanism enable physicians in many cases to access the femoral artery percutaneously, without the surgical cut down currently needed. With this approach, a needle is inserted into the blood vessel through the skin, allowing the guide wire and delivery sheath to enter the artery with far less blood loss and trauma. The lower profile delivery sheath will also reduce the need for physicians to use more invasive conduits, surgical bypass grafts, to gain aortic access in patients with advanced atherosclerosis.

"The first U.S. placement of the Zenith Low Profile AAA endovascular graft marks an important step by bringing minimally invasive treatment options to a broader set of patients worldwide," said Phil Nowell, global leader of Cook's aortic intervention strategic business unit. "The new Zenith system is a major advancement in Cook's endograft and delivery system technology. If approved, it will equip physicians with a superbly designed and crafted tool that offers the clinical benefits of Zenith, which is already the world leader in sales, with the advanced flexibility to treat a far larger subset of patients suffering from AAA using EVAR."

The trial is designed to evaluate the safety and effectiveness of the small endograft delivery system in 120 patients at 24 trial sites, Cook noted. Farber receives financial support from Cook to educate physicians in the proper use of the Zenith endograft system. Ronald Fairman, MD, chief of vascular surgery and endovascular therapy at the University of Pennsylvania (Philadelphia), serves as the trial's principal investigator.

While this trial is just getting underway, another Cook trial is wrapping up. The company said it has completed patient enrollment in its REFORM trial evaluating the company's Formula balloon expandable stent for renal artery stenosis. Cook says renal stenosis, a narrowing of the renal artery, can result in hypertension, renal atrophy, and kidney failure if left untreated.

"The REFORM trial completed enrollment in record time considering the small number of select investigative sites invited to participate in the trial," said Robert Bersin, MD, the trial's principal investigator and medical director of endovascular services at Seattle Cardiology and Swedish Medical Center. "The speed with which enrollment was completed speaks to the comfort the operators, including myself, have with the performance of this dedicated renal stent platform. The acute outcomes have been nothing but superb. The trial is now in follow-up and we are confident that long-term patient outcomes will be as good as the acute outcomes we observed."

Mark Breedlove, director of the vascular therapies technology unit, told MDD that the REFORM trial started in late February 2008 and the last patient was enrolled on May 1, 2009.

The trial enrolled 100 patients at seven investigative sites throughout the U.S. Initial clinical results on the trial's endpoint of revascularization of the target lesion to perfuse the kidney measured at nine-months post-procedure are expected to be available in the second quarter of 2010, and an FDA regulatory submission is expected to be made based on those data, Cook said.

"Cook has long been a leader in balloon and stent technology in the peripheral arteries, and the enthusiasm seen amongst clinical trial participants using our new Formula stent indicates that we are on the verge of bringing an advanced stenting technology to patients suffering renal artery blockages," said Rob Lyles, VP and global business unit leader of Cook's peripheral intervention division. "We look forward to timely completion of the clinical follow-up on these patients."

According to the company, balloon angioplasty has been the treatment method of choice for renal artery disease, but does not always result in permanent reopening of the narrowed blood vessel, prompting investigators to explore whether the use of a stent can result in better long-term patient outcomes.

The Formula stent has an "extremely low profile" that is lower than many cobalt chromium stent platforms, Cook noted. In addition, the stent does not shorten upon expansion, which can potentially improve accurate placement across the diseased lesion, Breedlove said.