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Intracoronary Stenting and Angiographic Restenosis Investigators – Test Efficacy of Rapamycin-Eluting Stents With Different Polymer Coating Strategies - ISAR-TEST-3
Description:
The goal of the trial was to evaluate treatment with biodegradable-polymer stents and polymer-free stents compared with sirolimus-eluting stents (permanent-polymer) among patients with obstructive coronary artery disease.
Hypothesis:
The use of biodegradable-polymer stents and polymer-free stents will be noninferior in preventing coronary restenosis.
Study Design
- Randomized
Patients Enrolled: 605
Mean Follow Up: 6-8 month angiographic follow-up, 1-year clinical follow-up
Mean Patient Age: 66
Female: 21
Mean Ejection Fraction: 54
Patient Populations:
Patients at least 18 years of age with ischemic symptoms or objective evidence of ischemia, and native coronary stenosis of at least 50%
Exclusions:
• Inability to obtain written informed consent
• Target lesion in the left main trunk or bypass graft
• In-stent restenosis
• Acute myocardial infarction
• Cardiogenic shock
• Malignancy or other comorbidity with resultant life span of less than 1 year
• Allergy to any of the study medications
• Pregnancy
Primary Endpoints:
In-stent late luminal loss
Secondary Endpoints:
• Binary in-segment restenosis
• Need for target lesion revascularization
• Death or myocardial infarction
• Stent thrombosis
Drug/Procedures Used:
Patients with obstructive coronary disease were randomized to a biodegradable-polymer stent (n = 202), a polymer-free stent (n = 201), or a sirolimus-eluting stent (permanent-polymer) (n = 202).
Concomitant Medications:
Prior to the intervention, all patients received 600 mg of clopidogrel. During the intervention, patients received intravenous aspirin, heparin or bivalirudin, and a glycoprotein IIb/IIIa inhibitor according to operator discretion. After the intervention, patients were treated with 200 mg of aspirin daily and 150 mg of clopidogrel daily for the first 3 months, then 75 mg of clopidogrel daily for at least 6 months.
Principal Findings:
Repeat angiography was performed in 81.3% of patients. Diabetes was present in 27.4% of the patients. There were 26% bifurcation lesions, 7.7% total occlusions, and 74.1% type B2 or C lesions by the American Heart Association/American College of Cardiology classification. The mean lesion length was 14.3 mm and the mean reference diameter was 2.75 mm.
The mean in-stent late lumen loss at 6-8 months was 0.17 mm in the biodegradable-polymer group (p < 0.001 for noninferiority vs. permanent-polymer), 0.47 mm in the polymer-free group (p = 0.94 for noninferiority vs. permanent-polymer), and 0.23 mm in the sirolimus group (permanent-polymer).
Binary restenosis at angiographic follow-up was 9.0% in the biodegradable-polymer group, 16.9% in the polymer-free group, and 10.8% in the permanent-polymer group. Target lesion revascularization at 1 year was 5.9% in the biodegradable-polymer group, 12.9% in the polymer-free group, and 7.9% in the permanent-polymer group.
Death or myocardial infarction at 1 year was 2.5% in the biodegradable-polymer group, 4.0% in the polymer-free group, and 3.5% in the permanent-polymer group. Definite stent thrombosis at 1 year was 0% in the biodegradable-polymer group, 1.0% in the polymer-free group, and 0.5% in the permanent-polymer group.
Interpretation:
The use of a biodegradable-polymer or polymer-free sirolimus-eluting stent is feasible. The use of a biodegradable-polymer sirolimus-eluting stent is noninferior regarding late lumen loss compared with a commercially available sirolimus-eluting stent (permanent-polymer); however, a polymer-free sirolimus-eluting stent is inferior to a permanent-polymer sirolimus-eluting stent in preventing late lumen loss.
This is an important study for helping to answer what the optimal release kinetics of an antiproliferative agent should be. According to the study investigators, sirolimus is eluted in 2 weeks with the polymer-free stent. This time frame may be too short since the polymer-free stent had the numerically highest target lesion revascularization rate and was inferior to the permanent-polymer stent in preventing late lumen loss.
On the other hand, the biodegradable-stent releases sirolimus over 6-9 weeks. This stent was noninferior to the permanent-polymer stent in preventing late lumen loss, and it showed the numerically lowest target lesion revascularization rate. A biodegradable-polymer stent could theoretically have the advantage of preventing late stent thrombosis. An appropriately powered study is needed to address these safety and efficacy questions.
References:
Mehilli J, Byrne RA, Wieczorek A, et al., on behalf of the Intracoronary Stenting and Angiographic Restenosis Investigators – Test Efficacy of Rapamycin-eluting Stents with Different Polymer Coating Strategies (ISAR-TEST-3) Randomized trial of three rapamycin-eluting stents with different coating strategies for the reduction of coronary restenosis. Eur Heart J 2008;Jun 11:[Epub ahead of print].
Keywords: Myocardial Infarction, Follow-Up Studies, Coronary Restenosis, Thrombosis, Polymers, Sirolimus, Angioplasty, Balloon, Coronary, Diabetes Mellitus, Stents
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