BACKGROUND: Carvedilol is a direct inhibitor of vascular smooth muscle cell migration and proliferation through inhibition of mitogen-activated protein kinase activity and regulation of cell cycle progression. It produced an 84% suppression of neointimal hyperplasia in rat carotid angioplasty model, but no data are available regarding its effect on stent restenosis in patients. We tested whether a sustained oral administration of carvedilol reduces restenosis after coronary stenting in patients. METHODS: One hundred fifty nine patients were randomized to receive either carvedilol (50 mg/day, n=80) or atenolol (50 mg/day, n=79) at least 1 day before stenting and continued on the same medication over 3 months. The primary end point was angiographic restenosis (>50% diameter stenosis) at follow-up angiography. RESULTS: Baseline clinical and angiographic variables were similar between the carvedilol and atenolol group. The carvedilol dose was tolerable in most patients after adjustment of other medications, but reduced in 3 patients due to hypotension and dizziness. Angiographic follow-up was done in 137 patients (86%) and the restenosis rate was not different significantly between both groups (17.1% versus 19.4%, p=0.732). CONCLUSION: A sustained oral administration of carvedilol is not effective to reduce stent restenosis. With carvedilol targeting regulators of cell cycle progression and having a profound neointimal inhibition with a high blood concentration in an experiment, further investigations using a stent-based delivery to achieve a high local concentration may be warranted.
Administration, Oral ; Angiography ; Angioplasty ; Animals ; Atenolol ; Cell Cycle ; Cell Movement ; Coronary Restenosis ; Dizziness ; Drug Therapy ; Follow-Up Studies ; Humans ; Hyperplasia ; Hypotension ; Muscle, Smooth, Vascular ; Prospective Studies* ; Protein Kinases ; Rats ; Stents*