COBRA: Postdilation with Cryoplasty Reduces Restenosis in Diabetic SFA Lesions

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SAN FRANCISCO, CA—Using cryoplasty for postdilation following stent implantation reduces restenosis compared with conventional balloon angioplasty in diabetic patients with superficial femoral artery (SFA) disease. Results of the COBRA trial were presented during a late breaking trial session November 11, 2011, at the Transcatheter Cardiovascular Therapeutics scientific symposium.

Cryoplasty uses liquid nitrous oxide rather than saline to inflate the angioplasty balloon, cooling its surface temperature to approximately -10° C. Proponents of the technique have suggested it reduces restenosis by altering plaque response, reducing elastic recoil, and inducing apoptosis in smooth muscle cells.

For the COBRA (Cryoplasty Or conventional Balloon post-dilation of nitinol stents for Revascularization of peripheral Arterial segments) trial, researchers led by Subhash Banerjee, MD, of the University of Texas Southwestern Medical Center (Dallas, TX), studied 90 diabetic patients with severe intermittent claudication or critical limb ischemia (Rutherford stage 3 or above) and SFA disease treated with self-expanding nitinol stents. Patients were randomized to postdilation with cryoplasty (PolarCath Peripheral Dilatation System, Boston Scientific, Natick, MA; n = 45) or conventional balloon angioplasty (n = 45).

Primary Endpoint Met

Procedural success with the cryoplasty system, which consists of a balloon catheter, a nitrous oxide refrigerant cylinder, and a microprocessor-controlled inflation unit, was 100%, with a mean fluoroscopy time of 31.82 ± 20.30 min. The primary endpoint of binary restenosis at 12 months was significantly reduced in patients receiving cryoplasty (figure 1), with conventional angioplasty showing a cumulative hazard ratio of 2.39 (95% CI 1.19-4.78; P < 0.01). On subanalysis, cryoplasty also reduced 12-month restenosis in patients with CTO lesions and in those who received bilateral stent implantation, although the difference in the former group just missed statistical significance (table 1).

Table 1. COBRA Subanalysis: 12-Month Binary Restenosis

Ankle brachial index measurements improved from baseline to 12 months in both groups, but the difference was only significant in cryoplasty patients (0.59 ± 0.21 to 0.77 ± 0.30; P = 0.004). Improvements in walking impairment questionnaire scores, meanwhile, were significant in both the conventional angioplasty (P = 0.002) and cryoplasty (P = 0.005) groups.

Adverse events were low in all patients, with just 4 deaths (3 cryoplasty, 1 conventional balloon), no amputations, no surgical revascularizations, and no cases of MI, stroke, or CIN.

“In patients with diabetes presenting with life-style limiting claudication, postdilation of nitinol self expanding stents in the SFA using cryoplasty significantly reduced 12-month in-stent restenosis compared to conventional balloon postdilation,” Dr. Banerjee said. “However, my personal desire is to take these results further and look at potential ways of impacting stent postdilation strategies on endovascular treatment of symptomatic peripheral arterial disease not only with this technology but with upcoming new, emerging technologies.”

He clarified that in addition to cryoplasty’s apoptotic effects, “at the same time, it minimizes smooth muscle cell necrosis, and hence the [therapy’s] potential role in reducing new intimal proliferation and in-stent restenosis.”

Clinical Utility Still TBD

In a telephone interview with TCTMD, Hitinder S. Gurm, MD, of the University of Michigan Medical Center (Ann Arbor, MI), noted that “this study shows proof of concept, but the clinical utility needs to be established, and it really behooves the company to follow up with a larger study to show that this translates to clinical event reduction.” He added that such a study needs to focus on TLR and address the question as to, “How many of these patients actually had a clinical procedure performed because of restenosis?” Dr. Gurm said.

Still, he noted that the COBRA results are “quite promising,” and “if I [had] a diabetic with a long occlusion that I’m stenting, I would seriously think about using cryoplasty for postdilation.”

As far as the mechanism behind the therapy, this is more nebulous, Dr. Gurm noted. “This is one of the few fields that has not been investigated that well. They always claim that cryoplasty reduces apoptosis and smooth muscle cell hyperplasia, but the number of studies on that are scant,” he said. “I’ve not seen a well-done study that has looked into the mechanistic underpinnings of cryoplasty. The data are just not there, and that’s the thing that bothers me. The therapy is being used, and we didn’t even know up to this point whether it worked.”

Using the Blue Cross Blue Shield of Michigan Cardiovascular Consortium-PVI registry, Dr. Gurm estimated that cryoplasty was used in about 4% of all patients undergoing lower extremity revascularization in the state of Michigan in 2010.

Despite the lack of mechanistic data, Dr. Gurm indicated that he has no problem seeing wider adoption of the therapy if a larger study shows positive results. “It’s very easy and convenient to do, and it’s not a big leap of faith,” he said. “If someone could demonstrate that this actually translates to a reduction in clinical events, we would very easily see this used on a regular basis.”

Study Details

In COBRA, patients in the cryoplasty and conventional balloon groups were well matched in terms of baseline characteristics, with equally high levels of hyperlipidemia and hypertension. The mean Rutherford stage was 3 in all patients, with an average lesion length over 146 mm.

 

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Source:
Banerjee S. COBRA trial: Cryoplasty Or conventional Balloon post-dilation of nitinol stents for Revascularization of peripheral Arterial segments. Presented at: Transcatheter Cardiovascular Therapeutics 2011; November 11, 2011; San Francisco, CA.

 

Disclosures:

• Dr. Banerjee reports receiving grant or research support from Boston Scientific, Gilead, Relypsa, and The Medicines Company and consulting fees and/or honoraria from Boehringer Ingelheim, Cordis, Gilead, Medtronic, Sanofi-Aventis, and St. Jude.
• Dr. Gurm reports no relevant conflicts of interest.

 

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