Imatinib for Restenosis Prevention - Imatinib for Restenosis Prevention
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).
Patients Enrolled: 180
Mean Follow Up: One year
Mean Patient Age: Mean age 66 years
Mean Ejection Fraction: Baseline mean 55%
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.
Acute coronary syndromes, presence of severe kidney failure, or contraindications to the medication used in the trial.
Angiographic restenosis at follow-up, defined as stenosis ≥50%
Death or myocardial infarction (MI) and target lesion revascularization (TLR) at one-year follow-up.
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.
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.
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).
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.
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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