Symptomatic carotid stenosis

Randomised trial of endarterectomy for recently symptomatic carotid stenosis final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998 351(9113) 1379-1387. 

Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler M, Ringelstein EB. Dual antiplatelet therapy with clopidogrel and aspirin in s3miptomatic carotid stenosis evaluated using doppler embolic signal detection the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation 2005 lll(17) 2233-2240. 

The benefit of carotid endarterectomy for prevention of recurrent stroke has been studied previously in major trials.25,26 A recent meta-analysis has been completed that has combined these clinical trials to evaluate 6,092 patients.27 Carotid endarterectomy has been shown to be beneficial for preventing ipsilateral stroke in patients with symptomatic carotid artery stenosis of 70% or greater and is recommended in these patients. In patients with symptomatic stenosis of 50% to 69%, a moderate reduction in risk is seen in clinical trials. In all patients with stenosis of 50% to 69% and a recent stroke, carotid endarterectomy is appropriate. In other patients, surgical risk factors and surgeon skill should be considered prior to surgery. The patient should have, at a minimum, a life expectancy of 5 years, and the surgical risk of stroke and/or death should be less than 6%. Carotid endarterectomy is not beneficial for symptomatic carotid stenosis less than 50% and should not be considered in these patients. 

Most ischemic strokes are due to atherosclerotic cerebrovascular disease. Patients with symptomatic carotid stenosis of > 70% should be considered for endarterectomy. Aspirin is used for prophylaxis following transient ischemic attacks and minor stroke. 

Dittrich R, Ritter MA, Kaps M et al. (2006). The use of embolic signal detection in multicenter trials to evaluate antiplatelet efficacy signal analysis and quality control mechanisms in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial. Stroke 37 1065-1069... 

Chappell F, Wardlaw J, Best JKK et al (2006). Non-invasive imaging compared with intraarterial angiography in the diagnosis of symptomatic carotid stenosis a metaanalysis. Lancet 376 1503-1512... 

Cuffe R, Rothwell PM (2006). Effect of non-optimal imaging on the relationship between the measured degree of symptomatic carotid stenosis and risk of ischemic stroke. Stroke 37 1785-1791... 

Rothwell PM, Gibson R, Warlow CP on behalf of the European Carotid Surgery Trialists Collaborative Group (2000b). Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis. Stroke 31 615-621... 

However, without formal risk models, clinicians are often inaccurate in assessment of risk in their patients (Grover et al. 1995). Moreover, the absolute risk of a poor outcome for patients with multiple specific characteristics cannot simply be derived arithmetically from data on the effect of each individual characteristic such as age or severity of illness that is, one cannot simply multiply risk ratios for these characteristics together as if they were independent. Even if one could, it would still be rather complicated. In a patient with symptomatic carotid stenosis, for example, what would the risk of stroke without endarterectomy be in a 78-year-old (high risk) female (lower risk) with 80% stenosis who presented within two days (high risk) of an ocular ischemic event (low risk) and was found to have an ulcerated carotid plaque (high risk) ... 

Table 14.2. A Cox model for the five-year risk of ipsilateral ischemic stroke on medical treatment in patients with recently symptomatic carotid stenosis ...

Fig. 14.2. An external validation of the model detailed in Table 14.2 for the five-year risk of stroke on medical treatment in an independent randomized trial of endarterectomy versus medical treatment for symptomatic carotid stenosis (Rothwell et ai. 2005). Predicted risk of stroke on medical treatment is plotted against the observed risk of stroke in patients randomized to medical treatment in the trial (squares) and against the observed operative risk of stroke and death in patients randomized to surgical treatment (diamonds). Groups are quintiles of predicted risk.

Fairhead JF, Rothwell PM (2005). The need for urgency in identification and treatment of symptomatic carotid stenosis is already estahhshed. Cerebrovascular Diseases 19 355-358... 

External validity can also be affected if trials have protocols that differ from usual clinical practice. For example, prior to randomization in the trials of endarterectomy for symptomatic carotid stenosis patients had to be diagnosed by a neurologist and to have conventional arterial angiography, neither of which are routine in many centers. The trial intervention itself may also differ from that used in current practice, such as in the formulation and bioavailability of a drug, or the type of anesthetic used for an operation. The same can be true of the treatment in the control group in a trial, which may use a particularly low dose of the comparator drug or fall short of best current practice in some... 

Apart from patients with symptomatic carotid stenosis and endarterectomy, to date, only the Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence (FASTER) trial has addressed the difference between specific treatments administered early for patients with TIA and minor stroke (Kennedy et al. 2007). 

Rothwell PM, Gutnikov SA, Eliasziw M for the Carotid Endarterectomy Trialists Collaboration (2003). Pooled analysis of individual patient data from randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 361 107-116... 

Bond R, Rerkasem K, Shearman CP et al. (2004c). Time trends in the published risks of stroke and death due to endarterectomy for symptomatic carotid stenosis. Cerebrovascular Diseases 18 37-46 Bossema ER, Brand N, Moll EL et al. (2005). Perioperative microembolism is not associated with cognitive outcome three months after carotid endarterectomy. European Journal of Vascular Endovascular Surgery 29 262-268... 

Mayberg MR, Wilson E, Yatsu F for the Veterans Affairs Cooperative Studies Programe 309 Trialist Group (1991). Carotid endarterectomy and prevention of cerebral ischaemia in symptomatic carotid stenosis. Journal of the American Medical Association 266 3289-3294... 

Which patients have most to gain from surgery for symptomatic carotid stenosis ... 

Fig. 27.3. The effect of endarterectomy on the five-year risks of each of the main trial outcomes in patients with varying degrees of stenosis (< 30%, 30-49%, > 70% without near occlusion, and near occlusion) in an analysis of pooled data from the three main randomized trials of endarterectomy versus medical treatment for recently symptomatic carotid stenosis (Rothwell et al. 2003b).

Women had a lower risk of ipsilateral ischemic stroke on medical treatment and a higher operative risk in comparison with men. For recently symptomatic carotid stenosis, surgery is very clearly beneficial in women with > 70% stenosis, but not in women with 50-69% stenosis (Fig. 27.4). In contrast, surgery reduced the five-year absolute risk of stroke by 8.0% (95% Cl, 3.4-12.5) in men with 50-69% stenosis. This sex difference was statistically significant even when the analysis of the interaction was confined to the 50-69% stenosis group. These same patterns were also shown in both of the large published trials of CEA for asymptomatic carotid stenosis (Rothwell 2004). 

Prediction of risk using models requires a computer, a pocket calculator with an exponential function or internet-access (the ECST model can be found at www.stroke. ox.ac.uk). As an alternative, a simplified risk score based on the hazard ratios derived from the relevant risk model can be derived. Table 27.3 shows a score for the five-year risk of stroke on medical treatment in patients with recently symptomatic carotid stenosis derived from the ECST model. As is shown in the example, the total risk score is the product of the scores for each risk factor. Fig. 27.7 shows a plot of the total risk score against the five-year predicted risk of ipsilateral carotid territory ischemic stroke derived from the full model and is used as a nomogram for the conversion of the score into a risk prediction. 

Alternatively, risk tables allow a relatively small number of important variables to be considered and have the major advantage that they do not require the calculation of any score by the clinician or patient. Fig. 27.8 shows a risk table for the five-year risk of ipsilateral ischemic stroke in patients with recently symptomatic carotid stenosis on medical treatment, derived from the ECST model. The table is based on the five variables that were both significant predictors of risk in the ECST model (Table 27.3) and yielded clinically important subgroup-treatment effect interactions in the analysis of pooled data from the relevant trials (sex, age, time since last symptomatic event, type of presenting event(s) and carotid plaque surface morphology). 

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