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Pilot trial of oral rapamycin for recalcitrant restenosis
Prabhtej S Brara1, Mehran Moussavian, Mark A Grise
1Division of Cardiovascular Diseases, Scripps Clinic, 10666 North Torrey Pines Rd, La Jolla, Calif 92037, USA.
Background:
Sirolimus-coated stents are a promising new therapy for restenosis. We treated a select group of patients at especially high risk for restenosis with oral sirolimus.
Methods And Results:
Patients were treated with an oral sirolimus-loading dose of 6 mg after coronary angioplasty, followed by 2 mg/d for 4 weeks. Serum electrolytes, lipid profile, renal panel, and complete blood cell count were measured at 1, 3, and 5 weeks after drug initiation. Oral sirolimus was prescribed to 22 patients who had a total of 28 lesions and were at high risk for restenosis. Of the 22 study patients, 11 (50%) discontinued oral sirolimus early because of side effects or laboratory abnormalities. Hypertriglyceridemia and leukopenia were the most frequent adverse events, occurring in 3 patients each. All adverse drug effects were reversible after discontinuation. Follow-up was obtained in 100% of patients at a mean of 9.9+/-1.8 months, ranging from 6.5 to 11.8 months. Target lesion revascularization (TLR) occurred in 15 of 28 lesions (53.6%) and 13 of 22 patients (59.1%). There was no difference in TLR for patients receiving a complete course of sirolimus (n=8; 72.7%) compared with patients who terminated treatment prematurely (n=5; 45.5%; P=NS). Clinically driven repeat cardiac catheterization was obtained in 15 (68.2%) patients; restenosis (>50% diameter stenosis at follow-up) was present in 13 (86.7%).
Conclusions:
Oral sirolimus does not appear to provide benefit to patients with recalcitrant restenosis. Adverse drug effects are frequent, underscoring the importance of local drug delivery to achieve high tissue concentrations without systemic adverse drug effects.
Insights
Oral sirolimus did not benefit patients with difficult restenosis and frequently caused side effects. Local drug delivery may be a safer alternative for achieving therapeutic concentrations without systemic toxicity.
Area of Science:
- Cardiology
- Pharmacology
- Interventional Cardiology
Background:
- Sirolimus-coated stents show promise for treating restenosis.
- Oral sirolimus was investigated in high-risk patients to prevent restenosis.
Purpose of the Study:
- To evaluate the efficacy and safety of oral sirolimus in patients at high risk for restenosis.
- To assess adverse events and restenosis rates associated with oral sirolimus therapy.
Main Methods:
- 22 high-risk patients received oral sirolimus (6 mg loading dose, then 2 mg/d for 4 weeks).
- Laboratory tests (electrolytes, lipids, renal function, CBC) were monitored.
- Follow-up included clinical assessment and cardiac catheterization.
Main Results:
- 50% of patients discontinued oral sirolimus due to side effects (hypertriglyceridemia, leukopenia).
- Target lesion revascularization occurred in 53.6% of lesions and 59.1% of patients.
- Restenosis was present in 86.7% of patients who underwent repeat catheterization.
Conclusions:
- Oral sirolimus offers no apparent benefit for recalcitrant restenosis.
- Frequent adverse drug effects highlight the need for localized drug delivery to avoid systemic toxicity.
