Pilot study of oral rapamycin to prevent restenosis in patients undergoing coronary stent therapy: Argentina Single-Center Study (ORAR Trial).
Rapamycin-coated stents are associated with low restenosis rates, but the ability of oral rapamycin to prevent restenosis is unknown. From December 2001 through February 2002, thirty-four patients with 49 lesions were treated with oral rapamycin for 1 month following percutaneous coronary intervention (PCI) with bare stents. Patients received a loading dose of 6 mg rapamycin followed by a daily dose of 2 mg. Rapamycin blood levels were measured in all patients during the third week of treatment. Cholesterol and triglycerides were evaluated before and 1 month after treatment. A 6-month follow-up angiogram was performed in all patients. Angiographic binary restenosis (> 50%), target lesion revascularization (TLR), late loss, treatment compliance and major adverse cardiac events were analyzed independent of rapamycin levels. Baseline characteristics included a history of diabetes in 35% of patients and the presence of in-stent restenosis in 24.5% of lesions (12/49). The rapamycin was well tolerated and only 1 patient discontinued the therapy due to mild side effects. Angiographic restenosis and TLR at 6 months was present in 26.5% of lesions (13/49). Restenosis in de novo lesions was 18.9% (7/37) compared to 50% of in-stent restenotic lesions (6/12; p = 0.08). Restenosis in de novo lesions in patients with rapamycin levels > 8 ng/ml was 0% (0/12), whereas it was 24% (6/25) when the rapamycin levels were < 8 ng/ml (p = 0.07). Late loss was significantly lower when rapamycin levels were > 8 ng/ml (0.3 mm versus 0.9 mm, respectively; p = 0.04). Thus, in this observational study, oral rapamycin administered for 1 month after PCI with bare stenting was safe and well tolerated. Higher therapeutic rapamycin blood levels were associated with a lower late loss and a trend toward a lower restenosis rate in de novo lesions.
Rodriguez
Alfredo E
AE
Cardiac Unit, Otamendi Hospital, Buenos Aires, Argentina. centroceci@ sion.com
Alemparte
Maximo Rodriguez
MR
Vigo
Cesar F
CF
Pereira
Carlos Fernandez
CF
Llaurado
Claudio
C
Russo
Miguel
M
Virmani
Renu
R
Ambrose
John A
JA
D000284:Administration, Oral; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D023903:Coronary Restenosis / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000008:administration & dosage*; D015607:Stents
D007166:Immunosuppressive Agents; D020123:Sirolimus