Oral Rapamycin for Recalcitrant Restenosis - Oral Rapamycin for Recalcitrant Restenosis


The goal of the trial was to evaluate the safety and feasibility of the use of oral rapamycin after coronary angioplasty in patients at high risk for restenosis.


Oral rapamycin may be an effective alternative to local delivery for the prevention of restenosis.

Study Design

Study Design:

Patients Enrolled: 22
Mean Follow Up: Mean 9.9 months
Mean Patient Age: Mean age 57.1 years
Female: 36

Patient Populations:

Patients with in-stent restenosis and who had not responded to intracoronary radiation or patients who were not candidates for intracoronary radiation

Primary Endpoints:

Clinical restenosis requiring TLR

Secondary Endpoints:

Death, myocardial infarction, and target vessel revascularization

Drug/Procedures Used:

Following angioplasty, patients were treated with a 6 mg oral loading dose of sirolimus followed by 2 mg/d for four weeks.

Concomitant Medications:

Aspirin (325 mg/d) and clopidogrel (75 mg/d) indefinitely

Principal Findings:

Half of the patients in the trial (n=11) discontinued the oral sirolimus prior to the 30-day course of the medication due to side effects or laboratory abnormalities, with hypertriglyceridemia (n=3) and leukopenia (n=3) as the most frequent adverse events.

The primary end point of target lesion revascularization (TLR) occurred in 53.6% of lesions (15/28) and 59.1% of patients (13/22). The rate of TLR did not differ between patients receiving a complete course of sirolimus (72.7%, n=8) versus patients who stopped the medication early (45.5%, n=5; p=NS).

Restenosis, defined as >50% diameter stenosis, occurred in 86.7% (13/15) of patients who underwent clinically driven repeat cardiac catheterization. There were no deaths or myocardial infarctions during the follow-up.


Among patients at high risk for restenosis following coronary angioplasty, there was no apparent benefit associated with treatment with oral rapamycin.

The recent SIRIUS trial showed a significant reduction in restenosis and TLR associated with the rapamycin-eluting stent. This study sought to determine if oral, systemic delivery of rapamycin also reduced restenosis and the need for TLR, similar to the local delivery of rapamycin on drug-eluting stents. While this study was only a small pilot trial, no apparent benefit was observed with oral rapamycin, with more than half of patients undergoing TLR at a mean follow-up of 9.9 months. Additionally, only half of the 22 patients completed the study medication, due to side effects or lab abnormalities.

The authors speculate that the lack of benefit may be due to inadequate concentrations of the rapamycin at the tissue level of the artery, unlike a direct delivery via a drug-eluting stent. Conclusions from this study should be taken in context of the small sample size and nonplacebo-controlled and nonrandomized design of the study.


Brara PS, Moussavian M, Grise MA, et al. Pilot trial of oral rapamycin for recalcitrant restenosis. Circulation. 2003;107:1722-4.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Hypertriglyceridemia, Chronic Angina

Keywords: Myocardial Infarction, Follow-Up Studies, Leukopenia, Coronary Restenosis, Drug-Eluting Stents, Cardiac Catheterization, Hypertriglyceridemia, Constriction, Pathologic, Sirolimus, Angioplasty, Stents

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