Comparison between a sustained administration of carvedilol versus atenolol to reduce restenosis after coronary stenting

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 randomly assigned to receive either carvedilol (50 mg/d, N = 80) or atenolol (50 mg/d, N = 79) at least 1 day before stenting and continued on the same medication over a period of 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 but reduced in 3 patients because of hypotension or dizziness. Angiographic follow-up was done in 137 patients (86%), and restenosis rate was not different significantly between both groups (17.1% versus 19.4%, P = .732). Conclusions A sustained oral administration of carvedilol is not effective to reduce restenosis after stenting in patients. With carvedilol targeting regulators of cell cycle progression and having a profound neointimal inhibition with a high blood concentration in an animal study, further investigations with a stent-based delivery to achieve a high local concentration may be warranted.