Major efforts are underway to study the efficacy and safety of stents coated with drugs such as paclitaxel or sirolimus, which may prevent restenosis. Typically, the stent coating is a polymer that slowly dissolves, releasing the drug over a period of time.

An alternative method of drug delivery is to use the lipophilic properties of paclitaxel to treat vessels without the presence of polymer. This approach utilizes a metal stent that has a paclitaxel coating on its abluminal surface.

In European and Asian studies, this approach appeared reduced incidence of in-stent restenosis in coronary lesions. Accordingly, U.S. investigators attempted to replicate these findings in a larger, randomized comparison of a paclitaxel-coated stent versus a bare metal stent.

Investigators undertook the DELIVER trial to assess the effectiveness and safety of the paclitaxel-coated stent for treatment of de novo lesions in native coronary arteries ranging from 2.5 to 4 mm in diameter. Sponsors of the study included Guidant Corp. and Cook, Inc.

The main endpoint of the trial was target vessel failure at 270 days. Target vessel failure is the composite of death, myocardial infarction, and revascularization of the target lesion or vessel. A major secondary endpoint was in-stent angiographic binary restenosis at 240 days.

Dr. O’Neill reported results for 1,041 patients. The mean age of the patients was approximately 62 years and 70% were male. All patients received aspirin and clopidogrel before the procedure. During the procedure, they received heparin. Some received glycoprotein (GP) IIb/IIIa inhibitors at the discretion of the operator. After the procedure, patients received daily aspirin for at least 1 year and clopidogrel 75 mg/day for at least 3 months.

Results showed that the paclitaxel-stent produced a significant decrease in fibrointimal hyperplasia versus the uncoated stent. However, the magnitude of this effect was not large enough to meet pre-specified endpoints. For example, incidence of target lesion revascularization was 8.1% in the paclitaxel-coated stent arm and 11.3% in the bare metal stent arm (p=0.092). Likewise, angiographic binary restenosis occurred in 16.7% of patients in the paclitaxel-coated stent arm, versus 22.4% in the bare stent arm (p=0.149).

Target vessel failure at 270 days was 11.9% in the paclitaxel-coated stent arm and 14.5% in the metal stent arm (p=0.128).

The study at least shows that using a paclitaxel-coated stent is safe in this patient population. Investigators reported a 1% mortality rate for both the paclitaxel-coated and metal stents, and 1% incidence of major adverse clinical events at 30 days. The incidence of stent thrombosis and aneurysm were 0.4% and 0.9% respectively.

Investigators were not sure why they were unable to meet the pre-specified endpoints. Some speculate that there may be a drug-drug interaction between the paclitaxel and GP IIb/IIIa inhibiting agents. About 64% of the patients in the trial received a GP IIb/IIIa inhibitor during the procedure.

Furthermore, an increased dose of paclitaxel could improve efficacy. Dr. O’Neill said future research should focus on more optimal dose-response evaluation of this formulation.