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CLINICAL RESEARCH: CLINICAL TRIAL

Oral Rapamycin After Coronary Bare-Metal Stent Implantation to Prevent Restenosis

The Prospective, Randomized Oral Rapamycin in Argentina (ORAR II) Study

Alfredo E. Rodriguez, MD, PhD, FACC^_*,_*, Juan F. Granada, MD, Máximo Rodriguez-Alemparte, MD^_*, Cesar F. Vigo, MD^_*, Juan Delgado, MD, Carlos Fernandez-Pereira, MD^_*, Antonio Pocovi, MD^_*, Alfredo M. Rodriguez-Granillo, BS^_*, Daryl Schulz, RTN, Albert E. Raizner, MD, FACC, Igor Palacios, MD, FACC, William O'Neill, MD, FACC, Grzegorz L. Kaluza, MD, PhD, Gregg Stone, MD, PhD, FACC^|| for the ORAR II Investigators

^_* Otamendi Hospital, Buenos Aires, Argentina
The Methodist Hospital Research Institute, Houston, Texas
Massachusetts General Hospital, Boston, Massachusetts
William Beaumont Hospital, Royal Oak, Michigan
^|| Columbia University, New York, New York Dr. Delgado is now affiliated with the Corbic Research Foundation, Envigado, Columbia

Manuscript received October 21, 2005; revised manuscript received November 24, 2005, accepted December 13, 2005.

^_* Reprint requests and correspondence: Dr. Alfredo E. Rodriguez, Otamendi Hospital, Callao 1441 4 B, Buenos Aires, Argentina 1024 (Email: rodrigueza{at}sanatorio-otamendi.com.ar).

OBJECTIVES: The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation.

BACKGROUND: Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation.

METHODS: Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year.

RESULTS: Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p < 0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p < 0.001), and major adverse cardiovascular events (20% vs. 44%, respectively, p = 0.018).

CONCLUSIONS: This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Abbreviations and Acronyms   MACE = major adverse cardiovascular event   PCI = percutaneous coronary intervention   TLR = target lesion revascularization   TVR = target vessel revascularization

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