Role of oral rapamycin to prevent restenosis in patients with de novo lesions undergoing coronary stenting:: results of the Argentina single centre study (ORAR trial)

Objective: To assess the role of oral rapamycin in the prevention of coronary restenosis in patients undergoing coronary stenting. Methods: From December 2001 through February 2003, 76 patients with 103 de novo lesions treated percutaneously with bare stents received a loading dose of oral rapamycin 6 mg followed by a daily dose of 2 mg during 28 days in phase I (49 arteries in 34 patients) and 2 mg/day plus 180 mg/ day of diltiazem in phase II (54 arteries in 42 patients). Rapamycin blood concentrations were measured in all patients. A six month follow up angiogram was performed in 82.5% ( 85 of 103 arteries). Follow up angiographic binary restenosis (> 50%), target vessel revascularisation, late loss, treatment compliance, and major adverse cardiovascular events were analysed and correlated with rapamycin concentrations. Results: Rapamycin was well tolerated and only three patients discontinued the treatment for mild side effects. Angiographic restenosis was found in 15% of the arteries with angiographic restudy (13 of 85). The target vessel had been revascularised at follow up in 13.6% of the 103 vessels initially treated (14 of 103) and in 18.4% of the 76 patients (14 of 76). In-stent restenosis in phase I was 19% compared with 6.2% in phase II (p = 0.06). Angiographic in-stent restenosis in lesions of patients with rapamycin blood concentrations > 8 ng/ml was 6.2% and with rapamycin concentrations, 8 ng/ml was 22% (p = 0.041). Late loss was also significantly lower when rapamycin concentrations were > 8 ng/ml (0.6 mm v 1.1 mm, p = 0.031). A Pearson test showed a linear correlation between follow up late loss and rapamycin blood concentration (r = 20.826, p = 0.008). Conclusion: Oral rapamycin administered for one month after percutaneous coronary intervention was safe and with few minor side effects. High rapamycin blood concentrations were associated with significantly lower late loss and angiographic in-stent restenosis.