Stenosis of the coronary arteries may be treated by balloon dilatation followed by the implantation of a metal stent. However, restenosis occurs in 10-20% of patients treated with bare metal stents (BMS). Restenosis and treatment of restenosis is associated with risk of myocardial infarction (MI) and death. Drug eluting stents (DES)release drugs to the vessel wall that delay or inhibit the process of restenosis. Some reports have found that DES are associated with risk of acute stent thrombosis, MI and death. The precise magnitude of this risk is not known. Current evidence is therefore insufficient to balance the long-term risk and benefit of BMS vs DES.

The purpose of this trial is to compare the long-term effects on MI and total mortality of BMS vs DES. The trial will recruit 8000 patients from 8 Norwegian hospitals. The patients will be randomized to treatment with BMS or DES. Clinical events will be registered for 5 years after treatment. The study hypothesis is that there is no difference in the risk of death or myocardial infarction after treatment with BMS vs DES. The trial is initiated and run by university researchers and is sponsored by not-for-profit organizations.

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)