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Imatinib for Restenosis Prevention - Imatinib for Restenosis Prevention
Description:
The goal of the trial was to evaluate the efficacy of treatment with imatinib, a platelet-derived growth factor (PDGF) receptor kinase inhibitor, compared with placebo among patients with in-stent restenosis (ISR).
Study Design
Study Design:
Patients Enrolled: 180
Mean Follow Up: One year
Mean Patient Age: Mean age 66 years
Female: 21
Mean Ejection Fraction: Baseline mean 55%
Patient Populations:
Angiographically significant ISR, defined as lumen renarrowing of ≥50% at a previously stented segment, in a native coronary vessel along with angina pectoris or positive stress test.
Exclusions:
Acute coronary syndromes, presence of severe kidney failure, or contraindications to the medication used in the trial.
Primary Endpoints:
Angiographic restenosis at follow-up, defined as stenosis ≥50%
Secondary Endpoints:
Death or myocardial infarction (MI) and target lesion revascularization (TLR) at one-year follow-up.
Drug/Procedures Used:
Two days before repeat intervention and following diagnosis of ISR on diagnostic angiography, patients were randomized in a double-blind manner to treatment with oral imatinib (600 mg/day) (n=89) for 10 days or placebo (n=91). Conventional angioplasty was performed to treat the ISR, with stenting allowed in the presence of a suboptimal result or a large residual dissection. Repeat angiography was performed at a median of 198 days.
Concomitant Medications:
Clopidogrel 600 mg at least 2 h before and 500 mg intravenous aspirin immediately before the intervention; following the intervention, clopidogrel 75 mg (for at least 6 months) and 100 mg aspirin twice daily indefinitely.
Principal Findings:
Diameter stenosis at baseline was 65%. Diffuse restenosis was present more frequently in the placebo group (52.7% vs 37.1%, p=0.03). Revascularization was performed using balloon angioplasty in 92% of patients, with new stent placement in the remaining 8%. Drug-related side effects were frequent in the imatinib group (22.5%), predominantly gastrointestinal events. Serum creatinine at the end of the 10 day treatment were higher in the imatinib group compared with placebo (1.56 mg/dl vs 1.29 mg/dl, p<0.001).
There was no difference between groups in the primary endpoint of binary angiographic restenosis at follow-up (38.8% for imatinib vs 41.3%, relative risk 0.94, p=0.75). There was also no difference in diameter stenosis (44.0% vs 43.0%, p=0.75), late lumen loss (0.59 mm vs 0.60 mm, p=0.92), or net lumen gain (0.54 mm vs 0.67 mm, p=0.15). At one year clinical follow-up, there were no deaths; MI occurred in 1.1% of patients in both groups. Target vessel revascularization did not differ by treatment group (28.1% for imatinib vs 28.6% for placebo, p=0.94), nor did the composite of death, MI or TVR (29.2% vs 29.7%, p=0.95).
Interpretation:
Among patients with in-stent restenosis, treatment with oral imatinib, a platelet-derived growth factor receptor kinase inhibitor, was not associated with a difference in binary restenosis at angiographic follow-up compared with placebo.
Several studies have evaluated oral therapies for prevention of restenosis but all have had limited or no benefit. Pre-treatment with high dose oral sirolimus was associated with a reduction in recurrent restenosis in the OSIRIS trial, but no treatment effect was seen with usual-dose sirolimus. In contrast to oral therapy, drug-eluting stents have been shown to be associated with reduced rates of restenosis compared with balloon angioplasty among patients with in-stent restenosis in the ISAR-DESIRE trial.
References:
Zohlnhöfer D, et al. A Randomized, Double-Blind, Placebo-Controlled Trial on Restenosis Prevention by the Receptor Tyrosine Kinase Inhibitor Imatinib. J Am Coll Cardiol 2005;46:1999–2003.
Keywords: Risk, Follow-Up Studies, Coronary Restenosis, Drug-Eluting Stents, Pyrimidines, Piperazines, Sirolimus, Constriction, Pathologic, Creatinine, Receptors, Platelet-Derived Growth Factor, Protein Kinase Inhibitors, Benzamides, Exercise Test
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