Treatment of Hyperlipidemias

Clinical trials analyzing the relationship of lipid lowering strategies and stroke have yet to confirm a reduction in risk for patients with TIA or stroke. For TIA and stroke-free subjects, a recent meta-analysis of 16 trials of lipid lowering using the new statin agents has found significant reductions in stroke risk. A 29% reduced risk of stroke and a 22% reduction in overall mortality was found. Secondary prevention trials showed a 32% stroke risk reduction and primary trials a 20% reduction. In the Scandinavian Simvastatin Survival Study there was a significant reduction in fatal and nonfatal stroke among persons treated with hypercholesterolemia, as well as a clear reduction in total mortality and cardiac events. Lipid lowering strategies may be most beneficial in preventing those strokes attributed to atherosclerosis. Some clinical trials have demonstrated some exciting results regarding carotid plaque regression with lipid-lowering agents. The Asymptomatic Carotid Artery Plaque Study used serial carotid ultrasound measurements and demonstrated that control of modest elevations of LDL will retard the progression of asymptomatic carotid atherosclerotic plaque. Thus, observational and clinical trial data provide mounting support for the role of lipoproteins as precursors of carotid atherosclerosis and ischemic stroke, and the potential benefits of cholesterol lowering in stroke reduction. Patients with cholesterol above 200 and cardiovascular risk factors, should have a complete lipid panel and may require cholesterol lowering regimens.

Carotid Endarterectomy for Asymptomatic Carotid Stenosis

The efficacy of carotid endartectomy in asymptomatic carotid stenosis has been evaluated in three separate clinical trials: CASANOVA (Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin), Veterans Administration Asymptomatic Carotid Endartectomy Study, and ACASS (Asymptomatic Carotid Artery Surgery Study). While CASANOVA found no confirmatory data to support carotid endartectomy for treatment of asymptomatic carotid disease, this trial excluded all cases with high grade stenosis greater than 90%. The Veterans Administration trial confirmed a decrease in neurological events, specifically transient ischemic attack (outcomes reduced from 20% to 8%), associated with the carotid endartectomy treatment group versus the medical treatment group, but no significant reduction for ipsilateral stroke.

Patients eligible for ACASS were under age 80 with asymptomatic carotid stenosis greater than 60% and could not have any unstable cardiac disease. Centers were screened for the accuracy of carotid Duplex Doppler in detecting carotid stenosis greater than 60% and the expertise of the operating surgeons with established surgical morbidity and mortality of less than 3%. Overall, the 30-day ipsilateral stroke or death rate among the surgically treated patients was only 2.3%. The trial found a 5-year ipsilateral stroke risk of 10.5% among the medical group and 4.8% in the surgical group. There was a 55% risk reduction of ipsilateral stroke associated with carotid endarectomy. The benefit for men was greater than for women (risk reduction 69% vs. 16%). Further subgroup analyses are pending. Among those patients with asymptomatic carotid stenosis greater than 60% who have an acceptably low risk of operative complications, endarterectomy confers a significant reduction in stroke risk as long as the surgeon can maintain the operative risk below 3%.

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