OLIVE Registry: Endovascular Therapy Outcomes for CLI ‘Reasonable’ at 3 Years

In patients with critical limb ischemia (CLI) and infrainguinal lesions, endovascular therapy results in acceptable amputation-free survival at 3 years, according to a registry study published in the September 1, 2015 issue of JACC: Cardiovascular Interventions.

The outcome is “reasonable despite high reintervention and moderate ulcer recurrence rate,” write Masato Nakamura, MD, PhD, of Ohashi Medical Center (Tokyo, Japan), and colleagues. They had previously reported 12-month data from the multicenter OLIVE registry but say recent prospective trials “have not systematically studied the long-term durability of [endovascular therapy].”

The 312 patients (mean age 73.1 years; 65% men) in the registry underwent endovascular therapy at 19 centers in Japan from December 2009 to July 2011. Culprit lesions were below the knee in 42%, femoropopliteal in 17%, and a combination of the 2 in 41%. Overall, 88% of patients had tissue loss (15% Rutherford class 6), 15% wound infection, and 20% multiple wounds. Additionally, 63% were wheelchair users and 25% were bedridden.

Endovascular therapy consisted of provisional nitinol stenting on femoral lesions and balloon angioplasty alone on infrapopliteal lesions. Initial success, defined as straight-line flow to the foot, was achieved in 93%, with a procedural complication rate of 4.0%.

Shift in Predictive Factors Over Time

Amputation-free survival at 3 years (primary endpoint) was 55.2% and freedom from major adverse limb events (major amputation or major reintervention) was 84%.

Multivariable predictors of major amputation or death at 3 years were age, body mass index (BMI) ≤ 18.5, dialysis, and Rutherford class 6, while those associated with major adverse limb events were heart failure and Rutherford class 6. Use of statins and straight-line flow to the foot were predictors of good long-term limb prognosis (table 1).

The only predictor of major amputation or death at 3 years that had also been identified at 1 year was BMI ≤18.5. On Kaplan-Meier analysis, the highest risk for major amputation or death occurred in the first 6 months. The same pattern was seen for major adverse limb events.

Wound-free survival was 49.6%, with isolated below-the-knee lesions the strongest predictor of wound recurrence (OR 4.54; 95% CI 2.20-9.37).

Kaplan-Meier analysis confirmed an overall survival rate of 63% at 3 years, with rates of major amputation-free survival and freedom from reintervention of 87.9% and 43.2%, respectively.

According to the study authors, the emergence of different short- and long-term predictive factors seen in the registry “could be clinically useful in identifying the treatment goals that change over time for CLI patients with complex morbidity. Moreover, CLI due to isolated [below-the-knee] lesions was the only identified predicting factor for ulcer recurrence, suggesting the significance of foot care and meticulous outpatient follow-up.”

Call for Collaboration

The European BASIL trial remains the only prospective, randomized trial to compare endovascular therapy with surgical bypass in this population. In an editorial accompanying the study, Matthew T. Menard, MD, of Brigham and Women’s Hospital (Boston, MA), observes that the 3-year amputation-free survival rate in OLIVE is comparable to that found in both the surgical and endovascular therapy arms of BASIL, even though the registry included sicker patients.

Furthermore, the “shift in results from 1 to 3 years highlights the critical importance of longer-term data in accurately judging the best treatment for complicated CLI patients,” Dr. Menard writes, adding that the emergence of low BMI as a predictor of poor outcome at both time points  “is a novel and intriguing result.”

According to Dr. Menard, there is need for “a more cooperative approach to CLI care.” Specifically, a range of collaborating specialists with unique skill sets must be willing to work together in patients’ best interest, he says, adding that surgeons with lingering resistance to endovascular therapy must “be open to its evolving role,” while those who offer percutaneous treatment must “be willing to partner with their surgical colleagues.”

An example of this spirit, he observes, is the ongoing, randomized BEST-CLI study.

In a telephone interview with TCTMD, William A. Gray, MD, of Columbia University Medical Center (New York, NY), agreed that partnership is important since no single person has all the answers and multispecialty collaboration is almost certain to benefit the patient. But “too often an environment has been created that has been antagonistic and that has dampened and or eliminated the capacity to collaborate,” he cautioned. “For the sake of patients, that needs to go away.”

BEST-CLI is enrolling slowly and has many challenges, Dr. Gray added, “but my hope is that it will answer some additional questions not answered by the limited number of studies that have been done.”

He also noted that one of the biggest obstacles in treating CLI patients is the large number of comorbid conditions that can lead to death after endovascular therapy, and he congratulated the researchers on completeness of follow up in such a “challenging patient group.”

As for lower BMI being a predictor of poor outcome in the registry, the finding is “coherent and consistent with data from other sets of patients,” Dr. Gray added, noting that it also makes sense since nutrition is an important part of wound healing. Moreover, the finding’s consistency over time also provides important insight into the natural history of this disease and may be helpful for treatment planning, he said.

Sources: 
1. Iida O, Nakamura M, Yamauchi Y, et al. 3-year outcomes of the OLIVE registry, a prospective multicenter study of patients with critical limb ischemia. J Am Coll  Cardiol Intv. 2015;8:1493-1502.
2. Menard MT. Intermediate-term results of the OLIVE registry [editorial]. J Am Coll Cardiol Intv. 2015;8:1503-1505.

Disclosures:

• The study was funded by the Associations for Establishment of Evidence in Interventions. 
• Drs. Nakamura and Gray report no relevant conflicts of interest. 
• Dr. Menard reports being a national principal investigator of the BEST-CLI trial, which is funded by the National Heart, Lung and Blood Institute. 

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