Immunosuppressive Therapy for the Prevention of Restenosis After Coronary Artery Stent Implantation - IMPRESS

Description:

This double-blind, randomized, placebo-controlled trial evaluated the effects of oral prednisone on restenosis rate in patients with elevated C-reactive protein (CRP) levels 72 hours after coronary stent implantation.

Hypothesis:

Administration of immunosuppressive therapy to patients with evidence of significant inflammation after coronary stent implantation may decrease the rate of stent restenosis.

Study Design

Study Design:

Patients Screened: 527
Patients Enrolled: 83
NYHA Class: Patients with NYHA class >II were excluded.
Mean Follow Up: 12 months
Mean Patient Age: 40-80 years
Female: 17
Mean Ejection Fraction: Patients with ejection fraction <40% were excluded.

Patient Populations:

Patients were enrolled if they had typical angina or documented myocardial ischemia and underwent successful implantation of a single stent of a length less than 19 mm. Patients were required to have a normal CRP level (≤0.5 mg/dl) prior to stenting and an elevated CRP level (>0.5 mg/dl) after the procedure.

Exclusions:

Unstable angina; recent myocardial infarction; stenting of restenotic lesions, total occlusions, or vein grafts; connective tissue disease; renal failure; heart failure with New York Heart Association (NYHA) class >II; ejection fraction <40%; and recent steroid use or contraindication to steroid use

Primary Endpoints:

Survival free from death, myocardial infarction, or recurrence of symptoms requiring revascularization at 12 months

Secondary Endpoints:

Restenosis (in-stent stenosis ≥50%) and late loss (minimal luminal diameter after stenting minus the value at follow-up angiography)

Drug/Procedures Used:

Patients were randomly assigned to receive oral prednisone or matching placebo beginning 72 hours after stent implantation. The dose of prednisone was 1 mg/kg for 10 days, followed by tapering doses for a total of 45 days of therapy. Follow-up angiography was performed at six months or earlier if symptoms developed, and clinical follow-up extended to one year.

Concomitant Medications:

Patients received aspirin 325 mg daily indefinitely, ticlopidine 250 mg twice daily for four weeks, and pantoprazole 40 mg daily for 45 days. Beta-blockers, calcium antagonists, nitrates, statins, and angiotensin-converting enzyme (ACE) inhibitors were given at the discretion of the investigator. Of note, less than 40% of patients were treated with beta-blockers, and 12% were treated with statins.

Principal Findings:

Administration of prednisone was associated with a lower rate of clinical and angiographic restenosis. The primary clinical endpoint at 12 months was reached by 35% of patients in the placebo group and 7% of the prednisone group (p=0.0016 for event-free survival). The adjusted relative risk reduction of events associated with prednisone use was 0.15 (confidence interval 0.04-0.59, p=0.007). Angiographic follow-up was obtained in 98% of patients.

Restenosis rates were 33% in the placebo group and 7% in the prednisone group (p=0.001). Late loss and minimal lumen diameter values were significantly lower in the prednisone group compared with the placebo group.

Interpretation:

Administration of prednisone to patients with normal baseline CRP levels and persistently elevated CRP after coronary stent placement for low-risk stable angina was associated with a reduction in the primary endpoint of freedom from death, myocardial infarction, and revascularization after 12-month clinical follow-up. Repeat angiography at six months showed a significantly lower rate of stent restenosis in patients treated with prednisone. Limitations of this study include small size, restrictive inclusion criteria (83 patients enrolled out of 527 screened), and low rate of beta-blocker and statin therapy in the study population.

References:

Versaci F, Gaspardone A, Tomai F, et al. Immunosuppressive therapy for the prevention of restenosis after coronary artery stent implantation (IMPRESS study). J Am Coll Cardiol 2002;40:1935-42.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Inflammation, Risk, Myocardial Infarction, C-Reactive Protein, Follow-Up Studies, Prednisone, Coronary Restenosis, Angina, Stable, Coronary Angiography, Disease-Free Survival, Confidence Intervals, Stents


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