Cholesterol Lowering and Stroke Prevention

Sources: Crouse JR III, et al. Arch Intern Med 1997;157:1305-1310; Hebert PR, et al. JAMA 1997;278:313-321.


Recent studies have indicated the presence of hypercholesterolemia as a stroke risk associated with secondary risk of coronary heart disease (CHD) and have recommended the use of statin therapy to lower cholesterol levels in patients with consistent LDL values higher than 160 mg/dL. The statin agents recommended were lovostatin, pravastatin, and simvastatin/vasastatin.

The two more recent reports by Crouse and colleagues and Herbert and colleagues provide strong support for the statins to protect a wider group of patients than at first suspected. Crouse et al analyzed 88,647 patient years of statin treatment vs. no treatment in trials aimed at reducing hypercholesterolemia in either primary or secondary coronary heart disease (CHD). Average cholesterol reduction among treated patients lay between 26% and 32% except for a large Swedish cohort using simvastatin, which reduced the level by 38%. Reduced stroke risk ranged from zero to as high as 50% among the smaller groups of the primary CHD cohort, but averaged a 15% reduction per annum in the overall sample size of 7808 persons. Among the larger cohort of 11,710 persons involved in the secondary CHD trial, statin use induced an average per annum reduction in stroke rate of 31%. Unexplainable, however, is that among the total of the 13 study groups, six showed no relative reduction in stroke incidence. Sample size may be one reason: only one of those non-favorable groups included more than 1000 patients. The overall total outcome of treated/nontreated persons identified a 27% annual reduction in stroke rate among the treated ones.

Based on a literature search (not including the above data), the Hebert group reviewed the protective effects of statin included in 16 trials containing 29,000 subjects. Patients were followed for an average time of 3.3 years, and outcomes included analysis of protection for either primary or secondary stroke. They also analyzed the data for any hint of unexpected deaths or cancer in the treated arms of the study. Outcomes included a total incidence of 454 strokes. Patients receiving statins had a 30% reduction in low density lipoprotein cholesterol levels as well as a 29% reduction of strokes. No unexpected increase in noncardiovascular deaths or cancer occurred in either treated or non-treated patients.

Comment by Fred Plum, MD

The data in these two studies have been carefully collected and statistically well presented. We believe that neurologists should appropriately evaluate cholesterol levels in patients over 45 years of age, especially if they have hypertension or any evidence of carotid-vertebral arterial atherosclerotic disease. As mentioned in our earlier article on the subject, an orderly, cholesterol-lowering diet should be the first step of therapy, but the presence of fasting, low-density cholesterol levels that persist above 155-160 mg/dL deserve monitored treatment with currently introduced statins.