New Dual-Drug DES Adds Cilostazol to Boost Effectiveness of Paclitaxel

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A new drug-eluting stent (DES) that features a second drug, cilostazol, in addition to paclitaxel shows noninferiority to the standard Taxus stent, with angiographic outcomes similar to other DES currently in clinical use. Results of the small, randomized trial were published online February 8, 2011, ahead of print in the American Journal of Cardiology.

According to Seung-Jung Park, MD, PhD, of Asan Medical Center (Seoul, South Korea), and colleagues, the Cilotax stent (Cardiotec, Seoul, South Korea) was developed to increase the safety and efficacy of paclitaxel-eluting stents by including the antirestenotic agent cilostazol. The stent platform consists of cobalt chromium, and the drug-carrying polymers are a mixture of hydrophilic biocompatible cellulose acetate butyrate and bioabsorbable resomer.

For the study, the researchers randomized 111 patients with de novo coronary artery lesions less than 20 mm in length who were being treated at 2 South Korean centers to receive either Cilotax (n = 55) or paclitaxel-eluting Taxus Liberte (n = 56; Boston Scientific, Natick, MA) stents. Baseline characteristics were well matched between the 2 groups.

At 8-month angiographic follow-up, the Cilotax stent showed noninferiority compared with Taxus for the primary endpoint of in-segment late loss. Other parameters such as in-stent late loss and restenosis (in-stent and in-segment) were either improved with the Cilotax stent or equivalent between the 2 devices (table 1).

Table 1. Eight-Month Angiographic Outcomes

^a P for noninferiority; P = 0.056 for superiority.

At 8 months, rates of clinical outcomes were low and similar between the 2 groups. There were no cardiac deaths, MIs, or stent thromboses in either group. There was 1 noncardiac death with Taxus and none with Cilotax. Rates of TLR, TVR, and the composite of death, MI, or TLR were 3.6%, 3.6%, and 5.4% in the Taxus group vs. 1.9% for each endpoint in the Cilotax group (P = NS for each comparison).

“Despite the small number of patients, these findings suggest that a dual DES may improve the efficacy and safety of the paclitaxel-eluting stent,” the researchers conclude.

Cilostazol is an antiplatelet agent with a different mechanism of action from adenosine diphosphate receptor antagonists, selectively inhibiting phosphodiesterase III. It also has antiproliferative effects against vascular smooth muscle cells, the paper reports. Most of the cilostazol (6 µg/mm²) incorporated in the Cilotax stent is released within 3 months, while most of the paclitaxel (1 µg/mm²) is released within 1 month.

Outcomes Similar to Cypher, Xience V

Although the current group of patients had relatively simple lesions, the study authors note that the Cilotax stent, because of its low late loss, may ultimately find a role in patients with more complex stenoses. But larger studies geared toward clinical outcomes must be performed first to confirm the current findings, they stress.

In an e-mail communication with TCTMD, Dr. Park indicated that the angiographic outcomes of the Cilotax stent are similar to other DES in current use. “Based on the published data, angiographic efficacy values of the Cilotax stent are similar to those of the Cypher or Xience V stent,” he said. “In terms of clinical outcome (safety), I think more studies are needed.”

He added that cilostazol has “unique pharmacologic effects,” including antiplatelet, antiproliferative, and endothelial cell protective effects, that give the drug “potential synergisms with paclitaxel (reduction of restenosis, decreased risk of stent thrombosis, etc).”

Nevertheless, recent studies such as CILON-T have shown that while cilostazol can help reduce platelet reactivity when added to dual antiplatelet therapy in PCI patients, this change does not translate to improved outcomes. But Dr. Park was undeterred by such findings. “CILON-T is a relatively small trial with clinical follow-up,” he said. “There are many [other] studies to support the antirestenotic or antithrombotic effects of cilostazol.”

Dr. Park reported that a large-scale safety trial of the Cilotax stent is currently being planned.

Study Details

The median patient age in the study was 63 years, and the mean lesion length was 13.54 ± 4.40 mm. All patients were prescribed aspirin (100-200 mg/day) indefinitely and clopidogrel (75 mg/day) for at least 12 months. Stent implantation was successful in all patients.

 

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Source:
Lee CW, Park D-W, Seung KB, et al. Comparison of dual drug-eluting Cilotax stent and paclitaxel-eluting Taxus Liberte stent in native coronary artery lesions. Am J Cardiol. 2011;Epub ahead of print.

 

 

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