September 01, 2016
4 min read

Consensus on best treatment strategy for CLI requires additional research

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Chronic critical limb ischemia is a highly morbid and incapacitating condition, and an understanding of its epidemiology and current treatment options is essential to providing the best care for affected patients, according to a recent systematic review.

The review, written by Alik Farber, MD, and Robert T. Eberhardt, MD, both from Boston University Medical Center, is the result of a comprehensive search of literature published on the subject between 1980 and 2016.

“Critical limb ischemia represents the end stage of peripheral artery disease and is associated with impaired quality of life and high morbidity and mortality,” the authors wrote. “Its economic impact on the United States is significant, with annual health care costs estimated to be greater than $4 billion.”

The researchers detailed the latest findings on prevention and treatment of critical limb ischemia (CLI).

Defining CLI

The review defined CLI as a condition of arterial insufficiency characterized by chronic lack of tissue perfusion at rest. Chronic CLI manifests as ischemic rest pain, ulcers or gangrene accompanied by objective hemodynamic evidence of arterial insufficiency. The authors cited a recently published multidisciplinary consensus definition, which provides hemodynamic measurements for determining CLI. This document defines CLI as an ankle pressure of less than 70 mm Hg in patients with tissue loss and less than 50 mm Hg in those with ischemic rest pain.

Ankle-brachial index (ABI) is a common means of determining PAD and can also be used to classify CLI. According to the authors, an ABI < 0.9 is an indicator of PAD, whereas an ABI < 0.4 is considered indicative of CLI.

Additionally, a CLI staging method was recently created by the Society for Vascular Surgery; this scheme is based not on perfusion alone, but also factors such as wound extent, ischemia and extent of concomitant foot infection. In this classification scheme, details are given on four stages of clinical limb threat associated with amputation risk.

PAD is frequently caused by progressive, diffuse and multisegmental atherosclerosis. Therefore, PAD is strongly linked to risk factors such as smoking, diabetes and high cholesterol. CLI is an end stage to PAD, and the progression from PAD to CLI is associated with risk factors such as smoking, diabetes, older age and chronic renal disease. With the current aging of the baby boomer population, the rates of progression to CLI are expected to increase, the researchers wrote. Currently, according to the review, between 5% and 10% of patients with asymptomatic PAD or intermittent claudication are expected to progress to CLI within 5 years.

Smoking cessation is considered an essential lifestyle modification for preventing progression from PAD to CLI.

Surgical CLI treatment

Revascularization is the standard treatment for CLI, and the two most common surgical methods are lower extremity bypass (LEB) and endarterectomy.

In cases of significant occlusive disease involving the common or deep femoral arteries, surgical endarterectomy is usually the favored approach. The use of common femoral endarterectomy has been found to yield 5-year primary patency rates of 90%, but a review of 1,843 solitary common femoral endarterectomies reported high rates of wound complication (8%) and return to the operating room (10%).

Most patients with CLI have substantial infrainguinal occlusive disease. Consequently, infrainguinal LEB has proven to be the gold standard of revascularization, boasting superior clinical durability and rates of limb salvage. A retrospective series of 2,058 patients treated with saphenous LEB yielded an 81% secondary patency rate at 5 years and a 95% limb salvage rate.

However, LEB has been linked to perioperative complications. In a review of roughly 10,000 LEB procedures, researchers found a 6.3% rate of graft thrombosis at 30 days and an 11.1% rate of surgical site infection.

Endovascular treatment

The past 2 decades have ushered in widespread adoption of endovascular techniques in most areas of cardiology, and CLI treatment has evolved in this direction as well.

Endovascular treatment for CLI has led to reductions in periprocedural morbidity and mortality, but questions remain about durability, cost and potential inappropriate use.

“A diverse group of practitioners, among them interventional cardiologists, interventional radiologists and vascular surgeons, provide treatment for patients with CLI,” the authors of the review wrote. “The decision to recommend surgical or endovascular revascularization varies among physicians based on a range of factors, external factors, access to an appropriate procedural environment and, perhaps most importantly, disparate treatment.”

An overall consensus exists that patients at high risk for surgical procedures may benefit from endovascular treatment, and patients with aortoiliac occlusive disease may reasonably be considered candidates for an endovascular-first approach. Ambiguity remains, however, regarding patients with infrainguinal PAD who are eligible for both surgical and endovascular intervention. Although some have advocated an endovascular approach for patients with CLI and infrainguinal PAD, clinical trials and registry studies have indicated a disadvantage associated with surgeries performed after a failed endovascular intervention.

The authors noted that, to date, only one randomized clinical trial, the BASIL trial, has been undertaken to compare surgical vs. endovascular revascularization for patients with CLI. Although this trial showed no difference in amputation-free survival between patients randomly assigned to LEB-first vs. balloon angioplasty first, initial randomization to LEB was linked to an improvement in overall survival at 2 years. No significant differences in cost or health-related quality of life were seen at long-term follow-up.

The need for additional data to guide decision-making regarding CLI revascularization modality has led to a new randomized clinical trial, the BEST-CLI trial. This multicenter, multidisciplinary, pragmatic, open-label, superiority trial will compare outcomes achieved with the best open surgical vs. the best endovascularization in patients with CLI and infrainguinal PAD. The study’s primary endpoint is major adverse limb event-free survival.

“This novel aggregate endpoint captures all major repeated vascular procedures on the index limb, including above-ankle amputation and major reinterventions, and as such, captures the therapeutic goals of treatment for CLI, including preservation of a functional limb and avoidance of major reinterventions that adversely affect quality of life,” the authors wrote. – by Jennifer Byrne

Disclosure: Farber and Eberhardt report no relevant disclosures.