Covidien Presents 12-Month DEFINITIVE AR Results

November 4, 2014—Covidien plc announced 12-month results of the DEFINITIVE AR study, which is designed to identify the clinical benefits of plaque removal using directional atherectomy followed by treatment with a drug-coated balloon (DCB). This randomized study included angiographic follow-up at 1 year to assess patency. Professor Thomas Zeller, MD, presented the data at the VIVA 2014: Vascular Interventional Advances meeting in Las Vegas, Nevada.

DEFINITIVE AR is a prospective, multicenter, randomized, pilot study that utilized the Covidien SilverHawk and TurboHawk directional atherectomy systems and the Bayer Healthcare peripheral paclitaxel-coated angioplasty catheter with Paccocath technology.

According to Covidien, the DEFINITIVE AR results demonstrated higher technical success and lower incidence of vessel injuries known as flow-limiting dissections. Additionally, the study suggests the combination of directional atherectomy and antirestenosis therapy (DAART) with DCBs improves patency in long and severely calcified lesions.

The company noted that directional atherectomy allows for the largest amount of luminal gain while maintaining vessel integrity. Longer lesions have lower patency across all current treatments, and presence of calcification may prohibit drug uptake and lead to less durability and loss of patency.

Covidien reported that duplex ultrasound primary patency rates for the long (> 10 cm) lesion subset at 12 months were 96.8% in patients treated with DAART compared to 85.9% in patients treated with DCB alone. Primary patency rates at 12 months in severely calcified lesions, per core lab assessment, were 70.4% in DAART patients compared to 62.5% in patients treated with DCB alone.

DAART resulted in 94.1% primary angiographic patency when more plaque was removed with directional atherectomy (< 30% residual stenosis was achieved) compared to 68.8% patency when less plaque was removed (> 30% residual stenosis) before treatment with the DCB.

The primary endpoint of the study was defined as the percent stenosis (narrowing of the vessel), at 1 year per angiographic core lab assessment. At 12 months, the percent stenosis in the randomized groups was 33.6 ± 17.7 for the DAART arm compared to 36.4 ± 17.6 for the DCB arm. These results were observational because the study was not powered to detect differences between the groups.  

In Covidien’s press release, Prof. Zeller commented, “DEFINITIVE AR was designed as a hypothesis-generating study to detect trends in treatment differences between patients who were treated with DAART and patients who were treated with DCB alone. While the use of DCBs to treat peripheral artery disease has demonstrated reduced restenosis, there have been limited clinical studies evaluating the effectiveness of DCBs in complex disease. The results suggest DAART may address an unmet clinical need in difficult to treat long or severely calcified lesions.” Prof Zeller is from the Universitaets-Herzzentrum in Bad Krozingen, Germany.

Professor Gunnar Tepe, MD, of Klinikum Rosenheim, Germany, added, “Lumen gain, or the amount of plaque removed from the artery with directional atherectomy prior to DCB treatment, may also be a critical factor in contributing to the long-term clinical success of DAART therapy. This data suggests when the optimal amount of plaque is removed, that is < 30% residual stenosis, the patency rate is improved.”

Ten investigational sites in Europe enrolled 121 patients in this observational investigation. There were 102 patients enrolled in the randomized cohort (DAART, n = 48; DCB alone, n = 54). The study also included 19 nonrandomized DAART registry arm for severely calcified lesions, however, calcification was present in all groups. The DEFINITIVE AR trial included adverse event review and adjudication by an independent Clinical Events Committee.

The primary outcome was target lesion percent stenosis at 1 year after initial treatment. Key secondary outcomes included primary patency by duplex ultrasound at 12 months after the procedure, primary patency by angiographic assessment at 12 months after the procedure, and assessment of major adverse events at 12 months after the procedure. Clinical follow-up occurred at predischarge, 30 days, 6 months, and 1 year postprocedure. Two-year follow-up is underway. 

The company stated that this small but rigorous pilot study suggests an added benefit for DAART over DCB in challenging lesion and that further investigation in larger, prospective, statistically powered randomized trials is warranted to confirm the positive trends observed in DEFINITIVE AR and to evaluate a possible economic advantage to a DAART strategy. Patients in DEFINITIVE AR will be followed out to 24 months to assess the durability of the results, advised the company.