Trial of Drug Eluting Stent Versus Bare Metal Stent to Treat Coronary Artery Stenosis

Background:

The balance of the long-term risks and benefits of coronary drug-eluting stents versus bare metal stents is not known.

Study objective:

The primary objective of the trial is to compare in a real-world setting the long-term effects on the incidence of death and myocardial infarction (composite primary end-point) after implantation of drug-eluting stents versus bare-metal stents. The secondary objective is to compare the long-term effects on the incidence of total death, cardiovascular deaths, major cardiovascular events, angina pectoris, revascularization procedures, and on health-related quality of life after implantation of drug-eluting stents versus bare-metal stents. The main tertiary objective is to assess the safety and efficacy in patient subgroups with specific demographic, clinical, and vessel- or lesion characteristics, and to conduct a cost-effectiveness analysis.

Study design:

This is a randomized, five-year prospective, multicenter, open-label clinical trial with blinded end point-evaluation.

Setting:

Investigator initiated trial conducted at 8 Norwegian interventional centres. The trial is sponsored by the Norwegian Research Council, the Regional Health Authorities and other not-for-profit organizations.

Randomization:

Patients will be randomized to receive either drug-eluting stent(s) or a bare-metal stent(s) in a 1:1 ratio.

Patients:

The trial will include 9000 patients with de novo lesions in native coronary arteries or by-pass grafts who meet the eligibility criteria. Men and women with stable angina pectoris or acute coronary syndrome will be included.

End-point:

The primary composite end point is total death and nonfatal myocardial infarction.Secondary end-points include total death and subcategories of death, fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, angina pectoris, revascularization, major bleeding, health-related quality of life.

Length of follow-up:

Five years.

End-points collected by electronic linkage to national registries:

The trial will use the unique Norwegian 11-digit person number to search the National Patient Registry and the National Death Registry for nonfatal and fatal end-points during follow-up, thereby minimizing loss to follow-up. Information on angina pectoris and health-related quality of life will be collected by questionnaires.

Statistical power:

The trial has a statistical power of 93 percent to detect a three percent (RR 1.176) absolute difference in incidence between the study groups, and a power of 64 percent to detect a two percent (RR 1.118) absolute difference, given a two-sided alpha value of 0.05.

Statistical analysis:

Statistical analyses will be conducted according to the intention-to-treat principle, and will be performed by using widely accepted statistical and/or graphical software.

Data collection:

Electronic Case Record Form (e-CRF)

Clinical Event Committee:

Adjudication of all end-points according to pre-specified and standardized criteria by Clinical Event Committee blinded to study assignment.

Expected Timelines:

First patient enrollment: September 2008 Last patient enrollment: February 2011 Completion of Follow-up: December 2014.

Inclusion criteria

• Men and women >18 years with stable angina pectoris or acute coronary syndrome
• The patient has consented to participate and has signed the patient informed consent form
• All lesions requiring intervention in one or more native coronary artery/coronary artery by-pass graft are amendable for implantation of drug-eluting stents only, or bare-metal stents only.
• The patient has a unique 11-digit Norwegian person number, is able to communicate in Norwegian, and is expected not to emigrate during study follow-up.

Exclusion criteria

• Previous implantation of a coronary bare metal stent or coronary drug eluting stent
• Planned intervention of a bifurcation lesion with overlapping 2-stent technique
• The patient has a serious medical condition (other than coronary artery disease) with a life expectancy less than 5 years
• The patient is currently participating in another randomized trial that clinically interferes with the present trial, or requires coronary angiography or other coronary artery imaging procedures
• Hypersensitivity or allergies to drugs or components in use with percutaneous coronary intervention
• Contraindications for treatment with clopidogrel/ticlid for 9-12 months
• Patient is receiving chronic anticoagulation therapy (e.g., warfarin, heparin)