EVAR Gets Slight Boost From U.K. Trial Results

By Mitchel L. Zoler

Midterm findings from two British studies of endovascular repair of abdominal aortic aneurysms may have limited relevance to U.S. practice because the aneurysms were relatively large at the time of intervention and the wait for surgery was long.

Despite these flaws, the findings offer another boost to the documented efficacy and safety of endovascular aneurysm repair (EVAR), which already is the preferred repair option in the United States, experts said. The findings also underscore the importance of reserving EVAR for patients who have aortic anatomy that's amenable to placement of an endovascular-repair device.

The results "validate the use of EVAR in properly selected patients," according to Jack L. Cronenwett, M.D., chief of vascular surgery at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

For elderly and higher-risk patients, the results "shift the balance in favor of EVAR, and many younger, lower-risk patients will now also shift toward EVAR to avoid the short-term morbidity of open repair."

"These data will be very helpful for giving patients a perspective on how the treatment works long-term," said Thomas S. Riles, M.D., chairman of the department of surgery and a vascular surgeon at New York University. "The more long-term data that we have, the easier it is for patients to make better choices. We currently do about 80% of our abdominal aortic aneurysm [AAA] repairs with EVAR, and as I look at these data, I think that maybe we should be a little more conservative. But if a group now does about 50% of their repairs with EVAR, maybe the results will push them to use EVAR more," he said in an interview.

According to Dr. Cronenwett, most American centers now use EVAR in about 60% of patients with AAAs that are large enough to warrant repair.

William D. Jordan, M.D., chief of vascular surgery at the University of Alabama, Birmingham, questioned the relevance of the two studies because the aneurysms were often large at the time of randomization (all AAAs had a diameter of at least 5.5 cm) and because many patients had long delays before surgery.

"In the U.S., you wouldn't have a practice if you waited 60 days before making a repair," he said in an interview with this newspaper.

The standard of care in the United States is to offer repair once an AAA reaches 5.0 cm in diameter, and with increasing use of routine surveillance, more patients are being diagnosed with AAAs of even smaller diameter.

Although the efficacy and safety of AAA repair for aneurysms that are 4.0-4.9 cm in diameter are now being studied in two trials, Dr. Jordan will currently repair an AAA of this size if the patient asks for it and is a suitable candidate. Some patients are too anxious to allow an AAA that's 4.0 cm or larger in diameter to go unrepaired, he said.

In addition, improving technology for assessing AAAs and in EVAR devices has probably made certain elements of the study outdated. For example, the anatomy of many AAAs in U.S. patients is now routinely assessed with CT scans and three-dimensional reconstruction to better assess the suitability of the proximal aortic neck for EVAR repair. This method for selecting patients who are best suited to EVAR was not available during the first years of the U.K. trials.

"Our research has stressed the value of three-dimensional reconstructions for endograft planning," Dr. Cronenwett told this newspaper.

The EVAR trials 1 and 2 were done at 34 hospitals in the United Kingdom, which assessed 4,799 patients with an AAA from September 1999 through December 2003. From this group, 1,423 patients had an AAA at least 5.5 cm in diameter and were judged eligible for either EVAR or open repair, and from this group a total of 1,082 were randomized and included in the primary end point analysis for trial 1. Among the more than 3,000 patients who were ineligible for randomization, 457 were deemed eligible for EVAR with an AAA at least 5.5 cm in diameter but unfit for open repair. Of these, 338 agreed to enroll in trial 2, which randomized the patients to EVAR or medical management.

The average age of patients in trial 1 was 74 years, and their median aneurysm diameter was 6.2 cm. The median time from randomization to surgery was 43 days in the EVAR group and 36 days in those who had open repairs. The EVARs were done using a variety of commercially available devices.

The investigators reported that by 30 days after surgery, patients treated with EVAR had 1.7% mortality, compared with 4.7% in those who got an open repair (Lancet 2004;364:843-8).

By the end of 2004, all patients had been followed for 1 year, 70% for 2 years, 47% for 3 years, and 24% for 4 years. At that point, the incidence of death from all causes was 100 out of 543 in the EVAR group (18.4%), and 109 out of 539 in the open-repair group (20.2%), a difference that was not statistically significant.

But aneurysm-related deaths occurred in 19 of the EVAR patients (3.5%), compared with 34 in the open-repair group (6.3%), a statistically significant difference. When the rate of aneurysm-related deaths was adjusted for clinical and demographic differences at baseline, EVAR was associated with a 49% drop in the rate of aneurysm-related deaths, compared with open repairs (Lancet 2005;365:2179-86).

Although aneurysm-related survival was better with EVAR, the procedure also led to more complications. By 4 years, 41% of patients in the EVAR group had at least one complication, compared with 9% among those who got open repair. The overall complication rate was 17.6/100 person-years with EVAR and 3.3/100 person-years with open repair. The most common complications of EVAR were a type 2 endoleak (in 79 patients) and a type 1 endoleak (in 27 patients). Reinterventions occurred at a rate of 6.9/100 person-years with EVAR, and 2.4/100 person-years with open repair.

In EVAR trial 2, the 166 patients randomized to EVAR had a median aneurysm diameter of 6.4 cm, and they waited a median of 57 days from their randomization until their procedure was done. While they awaited EVAR, nine of the patients experienced aneurysm rupture. Among the 172 patients who were randomized to medical management, 47 (27%) eventually had their aneurysm treated, either by EVAR or open repair.

During up to 4 years of follow-up in trial 2, there was no statistically significant difference between the two study groups in total mortality or in aneurysm-related mortality (Lancet 2005;365:2187-92).

The performance of EVAR in trial 2 was handicapped by two factors, Dr. Cronenwett said in an editorial that accompanied the two reports: First, there was a prolonged lag between randomization and the time was EVAR was done--a delay that probably led to the ruptures in nine patients who were awaiting their procedures. Second was the high rate of aneurysm repairs done in the patients who were randomized to medical management.

These two factors "bias the study against EVAR," he wrote (Lancet 2005;365:2156-8).

Despite this limitation, the message from trial 2 is that in patients who have a relatively short life expectancy, EVAR should be targeted to carefully selected patients, he said.

The message from trial 1 also involves patient selection, he wrote. Patients with low operative risk are the best candidates for open repair and should be considered for EVAR only if they have excellent anatomic suitability. According to Dr. Riles, that would mean a long, proximal, aortic neck, 1.5 cm or longer, and a width that's ideally no more than 28 mm.

Another issue is that the proximal aortic neck cannot be too angulated or tortuous. Patients with higher operative risk are generally better candidates for EVAR, but they still must have adequate aortic anatomy, Dr. Cronenwett wrote.

A relatively small fraction of patients with marginal anatomic suitability and a short life expectancy are best managed medically with no aneurysm repair. But a sizable fraction of patients fall into a gray area, where there is no clear advantage of EVAR or open repair. In these cases, patient preference is an important factor, he said.

Patient preference can be a key factor for even more patients. When patients are given the option of EVAR or open repair, the vast majority choose EVAR, Dr. Jordan maintained.

In fact, Dr. Riles noted, the data from the British trials will be useful for tempering the enthusiasm of some patients for EVAR by showing them that after EVAR is done, patients face an ongoing risk that a follow-up procedure will be needed.

'OUR RESEARCH HAS STRESSED THE VALUE OF THREE-DIMENSIONAL RECONSTRUCTIONS FOR ENDOGRAFT PLANNING.'