Peripheral artery disease of the lower extremities affects up to 8 million people in the United States and is especially common in people older than 50 years of age.1 The major symptoms of lower extremity peripheral artery disease range from intermittent claudication to ischemic rest pain to critical ischemia with major tissue loss.2,3 These symptoms can have a great impact on patient quality of life and may eventually lead to amputation of the affected limb.

Although bypass surgery was the former standard of care for iliac artery disease, endovascular treatments, particularly percutaneous transluminal angioplasty (PTA), are now much more commonly performed.4 PTA is well-suited for treating highly localized lesions in the iliac arteries.5 However, due to elastic recoil of the vessel, residual posttreatment stenosis, and vessel wall dissection, the results of PTA often lack long-term durability. Direct stent placement in the iliac artery has proven to be effective in overcoming the limitations of PTA and improving long-term patency6,7 and thus has become an increasingly more frequent treatment option. However, few randomized studies have shown clinical benefit of stenting over PTA.

Two types of stents may be used for treating iliac artery disease: balloon-expandable and self-expanding. The advantages of balloon-expandable stents include high radial force, precise placement, less foreshortening, and the possibility of further expansion. In contrast, selfexpanding stents offer greater flexibility and deliverability than their balloon-expandable counterparts. The Express LD Vascular Stent (Boston Scientific Corporation, Natick, MA), developed to treat iliac artery atherosclerosis, is a balloon-expandable stent that is designed to be flexible and conformable to the iliac vessel wall. The MELODIE trial was conducted to demonstrate the safety and efficacy of this stent, particularly with regard to long-term patency in iliac arteries.

TRIAL DESIGN
MELODIE was a prospective, single-arm, multicenter study that was designed to obtain safety and efficacy data for the Express LD Vascular Stent in the treatment of stenosed or occlusive atherosclerotic disease (de novo or restenosis) in iliac arteries.

Patient Selection
Between January 2004 and February 2005, 151 patients were enrolled at 10 study centers (nine were in Europe and one was in Canada). For inclusion in the trial, patients were required to have Fontaine class IIa, IIb, or III symptoms and a de novo or restenotic iliac artery lesion no longer than 10 cm in length with a visually estimated stenosis of ≥ 50%. The lesion had to be treatable with a maximum of two stents and have at least one patent ipsilateral runoff vessel. Patients with acute leg ischemia or Fontaine class I or IV symptoms were excluded from the trial, as were patients who had lesions with heavy calcification, excessive tortuosity, or lesions that were located within or near an aneurysm or in an area of persistent thrombus. Additional inclusion and exclusion criteria have been previously presented.8

Procedure
Before stent placement, diagnostic angiography was performed on each patient to assess the magnitude of the lesion and the availability of collateral vessels. Angiography was also performed after treatment to ensure that the stent was properly deployed and correctly positioned. During the course of the procedure, anticoagulant and/or antiplatelet therapy were administered based on the routine practice of the study center.

Patient Follow-Up
Patients in the MELODIE trial were required to have follow- up assessments at hospital discharge and at 30 days, 6 months, and 1 and 2 years after the procedure. Throughout the follow-up period, patients were required to take a daily dose of aspirin; clopidogrel or ticlopidine were substituted if aspirin was contraindicated. Ankle-brachial index measurements and symptom assessment based on the Fontaine classification were performed at all followup visits. In addition, arteriography was performed on each patient at the 6-month follow-up visit. Arteriograms were subjected to independent quantitative analysis at a core laboratory. Computed tomographic angiography was performed at the 1- and 2-year visits and was also analyzed by the core laboratory.

Study Objectives
The primary goal of the MELODIE study was to compare the angiographic mean percentage of lumen diameter loss with the Express LD Vascular Stent against a prespecified performance goal representative of outcomes with the Palmaz first-generation iliac stent (Cordis Corporation, Bridgewater, NJ). The Palmaz stent was chosen as the comparator because at the time the MELODIE trial was initiated, it was the only balloon-expandable stent approved by the US Food and Drug Administration for use in the percutaneous treatment of atherosclerotic disease in the iliac arteries. However, the Palmaz stent was not commercially available in Europe at the time of the study; therefore, a randomized study was not feasible. Other effectiveness parameters assessed across the study included lesion patency, technical and procedural success, and percent diameter stenosis.

Important clinical objectives included an analysis of MAEs (device- or procedure-related death, target lesion revascularization [TLR], and device-related distal embolization), as well as improvement in ankle-brachial index and patient symptoms, which were evaluated based on the Fontaine classification.

STUDY OUTCOMES
Patients and Lesions
The MELODIE trial enrolled and treated 151 patients with 163 lesions in 159 limbs. As shown in Table 1, the average age of enrolled patients was 60.1 years. Most were men who smoked currently or in the past and suffered from a level of claudication that left them unable to walk > 200 meters. A total of 13.9% had previous vascular surgery in the legs, and 12.6% had medically treated diabetes. The distribution of treatment in the iliac arteries is shown in Figure 1. Approximately 60% of the patients in the MELODIE trial required stenting of the external iliac artery.

Lesion-Based Results
Technical success and procedural success, as defined in Table 1, were achieved in 98% and 97.1% of treated lesions, respectively. In addition, the angiographically assessed 6-month mean percentage of luminal diameter loss plus upper confidence interval of 19.1% with the Express LD Vascular Stent was shown to be noninferior to a performance goal based on outcomes with the Palmaz iliac stent plus upper confidence interval (20%) (Figure 2).9 Thus, the primary endpoint in the MELODIE trial was achieved.

Furthermore, at 2 years after treatment, primary patency and assisted primary patency were maintained in 87.8% and 98.2% of patients, respectively (Figure 3).10 The durability of the results is also illustrated by the stability of the percent diameter stenosis through 2 years (Table 2).

MAEs
As illustrated in Figure 4A, the composite rate of MAEs in the MELODIE trial at 1 year was 11.1% plus an upper confidence boundary of 5.6%. This rate compared favorably to the literature-based performance goal for current- generation iliac stents of 19% (expected MAE rate + upper confidence interval). The components of the composite MAE rate include 30-day procedure- or device-related death, in-hospital myocardial infarction, 12-month TLR, and 12-month target limb amputation. No device- or procedure-related deaths occurred within 30 days postprocedure or over the entire 2-year course of the MELODIE trial. The individual rates of other adverse clinical events, as shown in Figure 4B, are low and acceptable. Through the 2-year follow-up period, the rate of TLR remained stable (Figure 5), and no patients had a distal embolization.

TLR in Clinically Relevant Subgroups
Patients with diabetes. Diabetic patients treated in the MELODIE trial had consistently higher TLR rates through 2 years compared with patients who did not have diabetes. Of the diabetic patients who had a TLR during the MELODIE trial, more than one-third occurred before hospital discharge. By comparison, none of the nondiabetic patients were reported to have had a TLR until later than 30 days postprocedure.

Patients treated in the external iliac artery. As shown in Figure 6, patients who were treated in the external iliac artery had a slightly greater rate of TLR events throughout the trial compared to patients who received treatment only in the common iliac artery.

Clinical Improvement
The vast majority of patients in MELODIE experienced significant improvement in clinical symptoms after iliac stenting. As shown in Figure 7, a total of 84.1% of patients had Fontaine class IIb symptoms or worse at baseline. At 2 years after the procedure, only 16.8% of patients had symptoms considered Fontaine class IIb or worse. Also, the mean ankle-brachial index pretreatment improved from a measurement of 0.63 ± 0.22 to 0.85 ± 0.22 at discharge (Table 3). This mean anklebrachial index measurement was sustained through the end of the study at 2 years.

CONCLUSIONS
In summary, patients in the MELODIE trial who were treated with the Express LD Vascular Stent experienced substantial and sustained improvements in Fontaine class clinical symptoms and ankle-brachial index through the entire 2 years of the trial. The percentage of patients with Fontaine class IIb symptoms or worse improved from 84.1% before the procedure to 16.8% at 2 years after the procedure (P < .0001). The 2-year ankle-brachial index remained significantly improved compared to preprocedure measurements (0.85 vs 0.63; P < .0001). The primary endpoint of 6-month mean percentage of luminal diameter loss was 16.2% and was noninferior to the performance goal (upper 95% confidence boundary of 19.1% vs performance goal of 20%; P = .0061). Primary patency rates were 92.1% at 6 months and were maintained at 2 years with a rate of 87.2%. The safety of the Express LD Vascular Stent was demonstrated by the complete absence of device- or procedure-related deaths or distal embolization in the MELODIE population throughout the entire trial. Furthermore, rates of major amputation, TLR, and in-hospital myocardial infarction were low and acceptable throughout the trial.

As expected, patients with diabetes had a somewhat higher rate of TLR throughout the trial and required revascularization procedures earlier compared to their nondiabetic counterparts. However, neither diabetic nor nondiabetic patients experienced distal embolization or device- or procedure-related death during the trial.

Patients treated in the external iliac artery had a higher rate of TLR through 2 years compared to patients who were only treated in the common iliac artery.

In conclusion, the 2-year results of the MELODIE trial show that the Express LD Vascular Stent is safe, effective, and durable in the treatment of stenosed or occlusive atherosclerotic common or external iliac arteries.

Jill S. Bleuit, PhD, is Senior Medical Writer, Boston Scientific Corporation in Marlborough, Massachusetts. She has disclosed that she is employed by Boston Scientific Corporation. Dr. Bleuit may be reached at (508) 683-4563; jill.bleuit@bsci.com.

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