COBRA Published: Cryoplasty Balloon Effective in Diabetic Patients with SFA Lesions

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Diabetic patients who receive nitinol stents for superficial femoral artery (SFA) disease typically experience high rates of restenosis after treatment. But adding another step to the procedure—post-dilation using a cryoplasty balloon rather than a standard angioplasty balloon—can reduce this risk over 1 year, according to a paper published online September 12, 2012, ahead of print in the Journal of the American College of Cardiology.

Results from the randomized COBRA (Cryoplasty Or conventional Balloon post-dilation of nitinol stents for Revascularization of peripheral Arterial segments) trial were previously presented at the 2011 Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA.

For the trial, Subhash Banerjee, MD, of the University of Texas Southwestern Medical Center (Dallas, TX), and colleagues studied 74 diabetic patients (16 required bilateral intervention; n = 90 lesions) with severe intermittent claudication or critical limb ischemia (Rutherford stage ≥ 3) and SFA disease treated with self-expanding nitinol stents. All lesions required stents greater than 5 mm in diameter and 60 mm in length, and half were totally occluded at baseline. Lesions were randomized to post-dilation with cryoplasty (PolarCath Peripheral Dilatation System, Boston Scientific, Natick, MA; n = 45) or conventional balloon angioplasty (n = 45).

Cold Reduces Restenosis

At 12 months, the primary endpoint of binary restenosis (≥ 2.5-fold increase in peak systolic velocity by duplex ultrasonography) was lower with cryoplasty than with conventional balloon post-dilation in the entire cohort, and a similar improvement occurred in lesions of patients requiring bilateral intervention. There also was a trend toward better results with cryoplasty in total occlusions (table 1). Overall, the cumulative risk of restenosis was more than doubled in lesions that underwent standard angioplasty (HR 2.28; 95% CI 1.14-4.61).

Table 1. Binary Restenosis at 12 Months

Five patients died during follow-up (3 cryoplasty, 1 conventional balloon, and 1 bilateral with both interventions), but none of the deaths were related to the index procedure.

Immediately after intervention, ankle-brachial index (ABI) improved from baseline for the cryoplasty group (from 0.60 ± 0.20 to 0.96 ± 0.14) and the conventional balloon group (from 0.59 ± 0.20 to 0.89 ± 0.21; P < 0.001 vs. baseline for both). ABI further improved by 12 months for cryoplasty-treated lesions (0.77 ± 0.30; P = 0.004) but returned to original levels for conventionally treated lesions (0.65 ± 0.26; P = 0.66). In addition, both groups showed reductions in Rutherford stage and gains in patient-reported walking ability over follow-up.

Building the Case

“Diabetic patients have more diffuse and angiographically more severe peripheral artery disease than nondiabetic patients. Femoropopliteal stenting remains highly prevalent among patients with diabetes mellitus, given the poor patency rates after balloon angioplasty or occluded SFA segments,” the investigators observe, explaining why diabetic patients were the target population of COBRA.

The mechanism behind cryoplasty remains unknown, Dr. Banerjee and colleagues acknowledge. However, they say “it is widely accepted that cryoplasty, by delivering cryotherapy precisely at -10° C to the arterial wall, induces smooth muscle cell apoptosis while limiting cell necrosis. In the present investigation, it was hypothesized that cryoplasty may reduce restenosis, especially in diabetic patients, who already have a greater smooth muscle cell proliferative response to vascular injury.”

In an editorial accompanying the paper, Anand Prasad, MD, of the University of Texas Health Science Center at San Antonio (San Antonio, TX), points out that cryoplasty via the PolarCath system has been commercially available since 2004. “The widespread adoption of this technology has been limited by mixed clinical data and a lack of fundamental understanding of cryobiology in relation to PAD,” he notes.

The unique post-dilation strategy employed in COBRA makes comparison with previous research challenging, Dr. Prasad says. Also limiting are the small size of the trial and lack of generalizability beyond the diabetic population, he adds. “Lastly, we cannot predict where the strategy outlined in the COBRA trial will fit in with the current and upcoming endovascular treatments for PAD [such as primary debulking, biodegradable technologies, and drug-eluting balloons]. With the concerns of stent fracture and restenosis, many interventionalists have migrated away from stenting.”

Diabetes, SFA Disease Pose Special Need

Dr. Banerjee told TCTMD in a telephone interview that the study’s takeaway message is that diabetic patients with PAD deserve focused attention. Rather than thinking of the COBRA results in terms of a specific device, he said, physicians should consider the overall strategy being tested. “[T]he extent of interventions performed in [diabetic] patients are not focal and include a large number of total occlusions and TASC C and D type lesions,” in which endovascular therapies have thus far led to suboptimal results, he explained. While cryoplasty achieved good results for these patients, restenosis levels “are still not where we want them to be.”

The interventional community must therefore dedicate more research into finding technologies and treatments that can help this patient subset, Dr. Banerjee urged.

Dr. Banerjee reported that his group plans to evaluate whether the strategy in COBRA is cost effective and, in the future, how cryoplasty might pair with DES dedicated to SFA disease. For now, he said, the technique is “readily available and very simple to perform” as a way of reducing restenosis.

Few, if Any, Drawbacks

In an e-mail communication with TCTMD, Hitinder S. Gurm, MD, of the University of Michigan Cardiovascular Center (Ann Arbor, MI), began with the caveat that as a pilot study, COBRA should be considered proof-of-concept prior to further validation. That being said, the results are “provocative and encouraging, and this technique merits further consideration,” he commented.

Dr. Gurm said that most clinicians would be able to perform the procedure and saw no drawbacks to cryoplasty for this indication. He agreed with the editorial that “stenting as a primary therapy is not so much in favor since there is no stent that is specifically designed to perform well long term under the mechanical strain unique to the femoral artery. Thus, many of us favor using angioplasty alone or some form of plaque ablation/removal as the first approach and reserve stenting for bailout.”

Based on the COBRA results, he said, “I can envision a scenario where I would try and avoid stenting when recanalizing an SFA, but when faced with the need to use a stent, I would consider cryoplasty for post-dilation.”

Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), also vouched for the feasibility of cryoplasty. However, he told TCTMD in a telephone interview, “it’s sort of a niche thing. There are some places that use it and some places that don’t.”

Further research will show whether cryoplasty can make a dent in clinical outcomes, he observed. Apart from some pain experienced by patients during the 2-minute balloon inflation, however, the only potential drawback might be cost. “Every time you add devices, that increases the cost of a procedure significantly,” Dr. Kirtane said, noting that even “balloons [for PAD] aren’t cheap.”

Study Details

Mean lesion length was 148 ± 98 mm, stented length was 190 ± 116 mm, and stent diameter was 6.1 ± 0.4 mm. Approximately half of patients in the cryoplasty arm underwent conventional balloon dilation of their stents prior to cryoplasty.

Sources:

1. Banerjee S, Das TS, Abu-Fadel MS, et al. Pilot trial of cryoplasty or conventional balloon post-dilation of nitinol stents for revascularization of peripheral arterial segments: The COBRA trial. J Am Coll Cardiol. 2012;Epub ahead of print.
2. Prasad A. Post-dilation of superficial femoral artery stents with cryoplasty: Does the COBRA trial take a bite out of diabetic restenosis? J Am Coll Cardiol. 2012;Epub ahead of print.

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• COBRA: Postdilation with Cryoplasty Reduces Restenosis in Diabetic SFA Lesions
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