Oral Sirolimus Reduces In-stent Hyperplasia
Sirolimus led to stomatitis in two patient groups but was tolerated overall.
Oral sirolimus (Rapamune, Wyeth) safely and effectively inhibited in-stent intimal hyperplasia in an open randomized study from Sao Paulo Hospital in Brazil.
The researchers, led by Valter C. Lima, MD, PhD, a cardiologist at the hospital, found the percent volumetric obstruction reduced in 36% of patients who received a dose of 2 mg/day and in 40% who received a dose of 5 mg/day.
Phase-3 studies should be undertaken to validate the results of this study, according to the researchers.
In-stent intimal hyperplasia
Lima and colleagues randomized 45 stable patients with coronary artery disease into three groups of 15 patients each. The first group did not receive sirolimus and served as a control.
The second group received 2 mg/day of sirolimus for 30 days and a loading dose of 6 mg before percutaneous coronary intervention (PCI); the third group received 5 mg/day of sirolimus for 30 days with a loading dose of 15 mg before PCI.
Efficacy
The primary endpoint of the study was intravascular ultrasound (IVUS) percent volumetric obstruction. IVUS outcomes showed 54.6% volumetric obstruction in control patients, 33.2% in patients who received the lower dose of sirolimus and 35.2% in patients who received the higher dose.
Volumetric obstruction corrected by stent length was 5.1 among control patients and 3.5 and 3.3 among patients who received the lower and higher doses of sirolimus, respectively (P < .05 lower- and higher-dose vs. control) (Figure).
Angiographic outcomes showed that control patients experienced a late loss of 1.31 mm; lower-dose patients, 0.78 mm; and higher dose patients, 0.85 mm. The loss index was 0.89, 0.45 and 0.49 for control, lower-dose and higher-dose groups, respectively (P < .05, lower- and higher-dose vs. control).
Patients who received sirolimus were able to tolerate the drug for 30 days, according to the study, despite stomatitis in eight lower-dose and seven higher-dose patients.
All PCI procedures were successful in the three groups. Two sudden deaths occurred: one at 3 months in a control patient and one at 6 months in a patient who received 5 mg/day of sirolimus.
Four control patients, three patients who received 2 mg/day of sirolimus and one patient who received 5 mg/day of sirolimus, needed target lesion revascularization. The difference among groups was not statistically significant, according to the study.
Study design
The target drug whole blood concentration in the lower-dose group was 5 ng/mL to 10 ng/mL, while in the higher-dose group, it was 10 ng/mL to 15 ng/mL.
All patients, regardless of randomized group assignment, were put on a regimen of 200 mg of daily aspirin indefinitely and 75 mg of daily clopidogrel for 30 days following a loading dose of 300 mg.
Eight months after PCI, patients underwent angiographic and intravascular ultrasound evaluations. 