The 2nd European Carotid Surgery Trial

Randomized trials have established the benefit of revascularisation by carotid
endarterectomy (CEA) for moderate and severe carotid stenosis. However, a risk
model derived from one of these trials and validated in another, showed that
only patients with a high risk of stroke under medical therapy benefited from
CEA. For a large range of patients there was neither clear benefit nor harm
from CEA. Medical therapy for stroke prevention has improved since these
original trials, with more widespread use of statins, more active lowering of
blood pressure and more effective antiplatelet regimes. Lower optimum targets
have been set for risk factor control e.g. blood pressure. Therefore CEA may
not be beneficial in many patients with carotid stenosis treated with modern
optimized medical therapy (OMT).

The aim of ECST-2 is to determine the best current regime for treating patients
with asymptomatic and symptomatic carotid stenosis who are at intermediate and
lower risk of stroke. Our main hypothesis is that patients who have clinical
characteristics that predict a 5-year risk of future stroke of <15% when
treated with modern optimized medical treatment (OMT) alone, will not benefit
from early revascularisation in addition to OMT, because any reduction in
future stroke rates after revascularisation will be balanced by an excess of
procedural stroke and death.
We propose that in the future it would be better if patients were routinely
selected for revascularisation on the basis of a detailed, up to date risk
assessment taking into account all the known risk factors.

ECST-2 is a multicentre, randomised, controlled, open, prospective clinical
trial with blinded outcome assessment. We will use a risk model based on
clinical characteristics to calculate a 5-year Carotid Artery Risk (CAR) score,
which will stratify patients as at high risk (>15%), intermediate risk
(7.5-15%), or low risk (<7.5%) of future stroke using predictive data from
previous trials. An interim analysis using MRI to determine rates of cerebral
infarction and haemorrhage at 2 years after randomisation will be performed to
assess safety and feasibility of the design and inform the design and sample
size calculations for the full trial.

carotid revascularisation (endarterectomy or, in exceptional cases, stenting) +
medication vs medication alone

The trial compares two existing forms of treatment currently used in many
hospitals. Hence, the trial is not an industry sponsored test of a new
treatment with unknown hazards. The trial protocol anticipates that some
patients may be harmed inadvertently as a result of revascularisation in the
trial and OMT is not expected to prevent all vascular events. Indeed, the
determination of the rate of these outcome events is a major aim of the trial.
However, we believe that the risks of these adverse events will be outweighed
by the benefits of treatment in either arm of the trial. The trial protocol
does not subject patients to hazards that the patient would not have
encountered if they had received the trial treatments outside the context of the
trial in routine practice.

In the first year after randomisation there will be four contact moments in the
AMC and one short telephone interview. After the first year there will be a
visit to the AMC once a year, with a minimum of 5 years and a maximum of 10
years. At each visit there will be blood withdrawal, carotid ultrasound,
physical examination and measurement of blood pressure. During the study a
patient will have three MRI's and three short memory tests and health
questionnaires.