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document
Randomized , double-blind , placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis : the Oral Sirolimus to Inhibit Recurrent In-stent Stenosis ( OSIRIS ) trial . BACKGROUND Despite recent advances in interventional cardiology , including the introduction of drug-eluting stents for de novo coronary lesions , the treatment of in-stent restenosis ( ISR ) remains a challenging clinical issue . Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy , the aim of the present double-blind , placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR . METHODS AND RESULTS Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms : placebo or usual-dose or high-dose sirolimus . Patients received a cumulative loading dose of 0 , 8 , or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days . Angiographic restenosis at 6-month angiography was the primary end point of the study . Restenosis was significantly reduced from 42.2 % to 38.6 % and to 22.1 % in the placebo , usual-dose , and high-dose sirolimus groups , respectively ( P=0.005 ) . Similarly , the need for target vessel revascularization was reduced from 25.5 % to 24.2 % and to 15.2 % in the placebo , usual-dose , and high-dose groups , respectively ( P=0.08 ) . The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up ( P < 0.001 ) . CONCLUSIONS In patients with ISR , an oral adjunctive sirolimus treatment with an intensified loading regimen before coronary intervention resulted in a significant improvement in the angiographic parameters of restenosis .
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
Sirolimus
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Intervention_Control
placebo
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Intervention_Pharmacological
usual-dose or high-dose sirolimus
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Intervention_Physical
6-month angiography
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Outcome_Physical
restenosis
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Outcome_Physical
neointimal hyperplasia
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Outcome_Physical
Angiographic restenosis at 6-month angiography
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Outcome_Physical
Restenosis
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Outcome_Other
need for target vessel revascularization
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Outcome_Physical
The sirolimus blood concentration
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Outcome_Physical
angiographic parameters of restenosis .
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Participant_Condition
in-stent restenosis
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Participant_Condition
ISR
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Participant_Sample-size
Three hundred
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Participant_Condition
symptomatic patients with ISR