In-Stent Restenosis Treated With Stent-Based Delivery of Paclitaxel Incorporated in a Slow-Release Polymer Formulation - TAXUS III

Description:

TAXUS III was a single-arm, two-center study evaluating the feasibility and safety of the TAXUS NIRx paclitaxel-eluting stent in the treatment of in-stent restenosis (ISR).

Hypothesis:

Treatment of ISR lesions with the TAXUS NIRx paclitaxel-eluting stent would be safe and would result in acceptable rates of MACE and restenosis.

Study Design

Study Design:

Patients Screened: 28
Patients Enrolled: 28
Mean Follow Up: 12 months
Mean Patient Age: Mean 63 years
Female: 32

Patient Populations:

ISR of a native coronary artery with objective evidence of ischemia. Angiographic inclusion criteria were lesion length ≤30 mm, 50-99% diameter stenosis, and vessel diameter 3.0-3.5 mm.

Exclusions:

Acute myocardial infarction; left ventricular ejection fraction <30%; stroke within six months; renal dysfunction; or contraindication to aspirin, clopidogrel, or ticlopidine

Primary Endpoints:

MACE (death, myocardial infarction, target-vessel repeat PCI, or CABG) at six and 12 months after the procedure

Secondary Endpoints:

Six-month quantitative coronary angiographic measurements of MLD, percent diameter stenosis, late loss (difference between the MLD after procedure and that at follow-up), and binary restenosis (>50% diameter stenosis within the target lesion); and intravascular ultrasound follow-up measurements including neointimal volume and percent volume obstruction

Drug/Procedures Used:

Percutaneous coronary intervention (PCI) with the TAXUS NIRx paclitaxel-eluting stent, with a slow-release copolymer carrier system that gives biphasic release of paclitaxel (initial release over the first 48 hours followed by slow release over 10 days). Stents were 15 mm long and 3.0 or 3.5 mm in diameter.

Concomitant Medications:

Periprocedural intravenous heparin was given to maintain an activated clotting time ≥250 seconds; all patients received aspirin and clopidogrel (300 mg loading dose followed by 75 mg once daily for six months).

Principal Findings:

A total of 28 patients with 28 target lesions were enrolled. Fourteen percent of patients had diabetes mellitus, the mean reference segment diameter was 2.75 mm, the mean lesion length was 13.6 mm, and 64% of lesions had a diffuse ISR pattern. Two stents were used in 46% of patients.

Procedural success was achieved in all patients. There were no cases of acute or subacute thrombosis. Six- and 12-month major adverse cardiac event (MACE) rates were identical (29%), driven largely by target vessel revascularization (six patients with PCI [21.4%] and one patient with CABG [3.6%]). Among the six patients who underwent repeat PCI, three patients met criteria for angiographic restenosis, while two patients had PCI due to incomplete stent apposition or underexpansion, and one underwent PCI due to symptoms with a small luminal diameter at follow-up.

Eighty-nine percent of patients underwent follow-up angiography at six months. The binary restenosis rate was 16% (four patients: two in a gap between two TAXUS stents, one in a bare metal stent used to treat an edge dissection, and one within a TAXUS stent), with an average percent diameter stenosis of 30.8%, and late loss of 0.54 mm. Further subgroup analyses demonstrated smaller minimal lumen diameter (MLD) and larger diameter stenosis in patients receiving two stents compared to one stent.

Interpretation:

Although small, this study demonstrates the first experience with the TAXUS paclitaxel-eluting stent for the treatment of ISR. Deployment of the stent appeared safe, with reasonable late loss and restenosis rates. However, the MACE rate (driven primarily by repeat target revascularization) and restenosis rates were significantly greater in this trial than seen in other trials of drug-eluting stents to treat de novo lesions, despite the relatively short lesion length and low risk profile of the patients enrolled.

These facts point to the difference in restenotic response of ISR lesions compared to de novo lesions. Furthermore, they suggest that despite the availability of potent therapies such as drug-eluting stents, repeat restenosis following intervention for ISR will continue to remain an active clinical problem, albeit a diminished one in the drug-eluting stent era.

References:

Tanabe K, Serruys PW, Grube E, et al. TAXUS III Trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation 2003;107:559-64.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Interventions and Coronary Artery Disease

Keywords: Paclitaxel, Coronary Artery Disease, Follow-Up Studies, Metals, Thrombosis, Drug-Eluting Stents, Constriction, Pathologic, Diabetes Mellitus, Percutaneous Coronary Intervention


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