Drug-Eluting Balloon Improves Outcomes in Diabetic Critical Limb Ischemia

Angioplasty performed with drug-eluting balloons lead to lower restenosis rates

In diabetic patients with below-the-knee critical limb ischemia, use of a drug-eluting balloon (DEB) for angioplasty lead to markedly lower restenosis rates at 1 year compared to conventional angioplasty with uncoated balloons. The findings were reported online ahead of print in Circulation.

“This is an important trial that helps solidify the thinking in Europe and that is now spreading in the United States that [DEBs] appear to be a significant advancement in the treatment of peripheral arterial disease,” said Vincent Bufalino, MD, a cardiologist and national spokesperson for the American Heart Association and Senior Vice President and Senior Medical Director of Cardiology-AMG, Advocate Health Care in Naperville, Illinois. “This is the first trial to show significant advances in therapy in patients with below-the-knee ischemia, which is the group we have had the most difficulty with,” he said. 

Dr. Bufalino noted that the therapeutic options for these patients have been subpar. “The approaches would fail leading to eventual amputations, multiple interventions, and surgical revascularizations,” he explained.

Randomized Studies on This Modality Are Lacking

The main results from this study, which were published in the June issue of Diabetes Care, showed a low 4-year cardiac mortality rate in this high-risk population from Arezzo, Tuscany, Italy, with no significant impact of critical limb ischemia [on mortality]. “We attribute these results to an aggressive limb and coronary revascularization strategy and to a strict clinical surveillance.” In addition, a low rate of major amputation (approximately 1% per year) was found. However, “the rate of target lesion revascularization in patients treated by conventional balloon angioplasty in below-the-knee lesions remained unacceptable (around 30% to 50%),” said lead author Francesco Liistro, MD, a physician at San Donato Hospital in Arezzo, Italy. Thus, the researchers decided to test whether use of DEB for angioplasty improved outcomes.

“We were frustrated by the lack of randomized, solid evidence in this difficult subset of patients,” Dr. Liistro said. “We focused our trial on the preservation of vessel patency, as repeat interventions with multiple contrast exposures are harmful in these sick patients with frequent life-threatening comorbidities.

Marked Reduction in Binary Restenosis Rate Found

In this open-label trial, diabetic patients with below-the-knee ischemia were randomized to paclitaxel DEB (n=65) or conventional percutaneous transluminal angioplasty with uncoated balloons (PTA; n=67). A single brand of DEB was used in this study.

The incidence of binary restenosis at 12 months—the primary outcome—was significantly lower in the DEB group than in the PTA group (27% vs 75%; P<0.001). In addition, DEB was linked to lower rates of target lesion revascularization (18% vs 43%; P=0.002) and target vessel occlusion (17% vs 55%; P<0.001).

“We were able to show a major reduction in the primary endpoint of binary restenosis (relative risk reduction [RRR], 64%) and of secondary endpoint of vessel occlusion (RRR, 68%). This effect size is so large that it has probably never been seen before in randomized trials of below-the-knee interventions,” Dr. Liistro said. “The advantage provided by the DEB also translated to a clinical benefit (higher rate of index ulcer healing), although our trial was not powered to address this question. This major advantage also was hinted at in a nonrandomized [study] (Schmidt et al. J Am Coll Cardiol. 2011;58[11]:1105-1109), which had a shorter follow-up of 3 months,” he noted.

Similar Rate of Adverse Events Observed

No major adverse events occurred during hospitalization. Eight patients died during the follow-up period, with no difference between the two groups in the rate of cardiac versus noncardiac deaths. One major amputation was performed on a patient in the PTA group. Thirty-six patients underwent minor amputations with no difference in rate between the two groups.

“These are still sick patients with advanced vascular disease, so that explains why there were still a number of deaths in both groups,” Dr. Bufalino commented. However, “if you can save these patients an amputation because you are able to get the blood flow down to their foot again, this is a big improvement,” he added.

The researchers currently are performing a 2-year clinical and ultrasonographic follow-up of this cohort. In the future, they hope to evaluate whether other DEB platforms lead to equivalent or improved results, Dr. Liistro said.

Dr. Bufalino concluded that, above all, physicians need to be more aggressive with early screening and detection of peripheral vascular disease in patients with diabetes and treat them before they get to the point where their limb is in jeopardy. “We have been remiss over the last several decades in that we have been focused on the heart and not as focused on the periphery,” he said.

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