Background
Atherosclerotic narrowing of the carotid arteries can cause stroke. In Europe at least one million people and about 100,000 people in the UK have severe stenosis (narrowing) in one or both or their carotid arteries.
ACST-1 (1993-2003) was an multi centre international trial comparing CEA with best medical treatment versus no immediate procedure. The trial randomised 3000 patients with substantial carotid artery disease but no recent neurological symptoms (stroke or TIA). The five year paper (May 2004) showed that carotid endarterectomy (CEA) reduced the risk of stroke when compared to best medical treatment alone.
Its successor, ACST-2, is a large simple international randomised trial comparing CEA with CAS in patients with asymptomatic carotid stenosis where there is substantial uncertainty which treatment is more appropriate. ACST-2 seeks to randomise such individuals between CEA and CAS to compare both the immediate hazards of the two procedures (1 month), and the subsequent stroke rates over the next 5 to 10 years.
ACST-2 can only succeed if many thousands of patients are randomised. The workload per patient has been minimised, so that the study can be integrated easily into routine health care.
The need for a large scale randomised trial comparing CEA vs CAS
A Cochrane meta-analysis of CEA vs CAS trials (mainly in symptomatic patients) stated that ‘the current evidence does not support a widespread change in clinical practice away from recommending CEA as the treatment of choice for suitable carotid artery stenosis. There is a strong case to continue recruitment in the current randomised trials comparing carotid stenting with endarterectomy'. Multicentre trials, undertaken mainly in symptomatic patients (eg, ICSS, SPACE, EVA-3S, CREST & SAPPHIRE ) have not yet resolved this uncertainty. Much larger trials are now needed, particularly in asymptomatic patients. The European Stroke Initiative recommendations for stroke management supported this, and stated that ‘carotid angioplasty (balloon dilatation), with or without stenting, is not routinely recommended for patients with asymptomatic carotid stenosis. It may be considered in the context of randomised clinical trials'.
Randomisation Started 15th January 2008.
Click for the Full ACST 2 Protocol (PDF) or the Summary Protocol (JPG image).
Treatments for patients with carotid artery stenosis
Medical treatment: Appropriate medical treatment with anti-platelet, anti-hypertensive and cholesterol lowering medicines helps to prevent both heart attack and stroke. In addition, interventional procedures can be used to reduce the stroke risk still further.
Carotid endarterectomy (CEA): In 1991 two large trials of CEA to remove carotid artery stenosis in ‘symptomatic' patients (ie, those who had had a stroke or stroke-like symptoms <6 months previously, irrespective of whether these still persist) showed that CEA reduced the risk of future stroke (ECST and NASCET 3&4 ). CEA is now widely used for stroke prevention in symptomatic patients. The first Asymptomatic Carotid Surgery Trial (ACST-1) and the Asymptomatic Carotid Atherosclerosis Study then investigated the role of CEA in 5000 patients with carotid stenosis, but with no stroke or stroke-like symptoms during the previous 6 months. In ACST-1 3000 patients were randomised between medical treatment only or medical treatment and ‘immediate' surgery. CEA involved a small (~3%) but definite peri-procedural risk of stroke or death, a substantial (~3% vs ~12%) reduction in the subsequent stroke rate over the next 5 years and a net 5-year gain (~6% vs ~12%) in the overall risk of stroke or peri-procedural death. The 5-year findings of ACST-1 are already changing surgical practice, and long-term follow-up of stroke rates continues.
Carotid artery stenting (CAS): CAS is a newer method of treating carotid stenosis whereby a catheter is passed from the groin up the femoral artery and aorta and into the narrowed carotid artery. A wire mesh stent is passed up the catheter and placed across the narrow portion of the artery. A balloon can then be inflated inside the stent to widen it and keep the artery open. The catheter and balloon are then removed. During stent placement some of the diseased artery may crumble, blocking the blood supply to the brain and causing a stroke. Compared with CEA, CAS avoids surgical wound discomfort, is usually performed under local anaesthetic, could shorten hospital stay, might reduce the risk of peri-procedural heart attack or stroke and may be more acceptable to the patient than surgery. There is, however, substantial uncertainty about the immediate hazards and long-term reliability of CAS compared to CEA.