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Statin Therapy Reduces Stroke Risk in a Range of Patients



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Am Fam Physician. 2004 Nov 15;70(10):2001-2004.

Although statin therapy has been associated with an approximately 25 percent reduction in coronary events, the impact on strokes is less clear. A possible positive effect on ischemic strokes in younger patients may be counterbalanced by a negative association with hemorrhagic stroke, especially in patients with high blood pressure. The Heart Protection Study, a large, prospective international trial, studied the effects on stroke of lowering blood cholesterol with statin drugs.

The study recruited more than 20,000 patients 40 to 80 years of age who had cholesterol levels of at least 135 mg per dL (3.50 mmol per L) and a history of diabetes or cerebrovascular, coronary, or occlusive arterial disease; men 65 and older with treated hypertension also were eligible. Exclusions from the study included patients with significant coronary or cerebrovascular events within the previous six months; hepatic, renal, or muscular problems; contraindications to statin therapy; and comorbid conditions that could increase mortality or cause compliance problems.

After screening, including laboratory testing and advice about risk factors for vascular disease, participants took placebos for a four-week “run-in” period. This step was followed by four to six weeks of treatment with simvastatin at a dosage of 40 mg daily. Compliant patients who had no contraindications were then randomly assigned to continue taking simvastin or to take a placebo for five years.

Patients were assessed in study clinics at four, eight, and 12 months, then every six months. The data collected included regular laboratory monitoring of participants and information about incident strokes, cardiovascular episodes, and other serious medical conditions. Data were collected from the records of primary care physicians, death certificates, and national registers of cancer, stroke, and other conditions in the participating countries. Strokes had to be confirmed as the cause of either neurologic deficit lasting more than 24 hours or death. Imaging or autopsy evidence was used to classify strokes into ischemic, hemorrhagic, and other categories. Rankin scores were used to classify the severity of each stroke.

A total of 3,280 patients with cerebrovascular disease and 17,256 other high-risk patients were included. Of those with cerebrovascular disease at entry to the study, 63 percent had a history of ischemic stroke, 46 percent had transient ischemic attacks, and 10 percent had undergone carotid surgery. Aspirin was used by 77 percent of participants with a history of cerebrovascular disease. Throughout the study, 85 percent of patients in the treatment group took simvastatin as prescribed. About 17 percent of the placebo group also received nonstudy statin drugs.

The overall reduction in stroke was 25 percent. This reduction was principally the result of a 30 percent reduction in ischemic strokes. The incidence of stroke in patients with a history of cerebrovascular disease was not improved by statin therapy, but stroke incidence fell by 34 percent in other high-risk patients. Rates of hemorrhagic strokes were comparable in the statin-treated and placebo groups. The reduction in strokes became apparent during the second year of the study. Significant reductions were noted in the incidence of transient ischemic attacks and carotid surgeries in all patients except those with preexisting conditions. Benefits also were noted in cardiovascular disease. Overall, a 24 percent reduction was noted in time to first coronary event in patients randomized to statin therapy. In patients with a history of cerebrovascular events, there was a highly significant 20 percent reduction in major vascular events in patients taking statins.

The authors calculate that simvastatin therapy reduced the rate of strokes in high-risk patients by about one fourth, and that with good compliance, it could reduce the rate by up to one third. They estimate that statin therapy prevented 16 first or subsequent strokes per 1,000 patients during the five-year follow-up period. The benefits of stroke prevention were equivalent in the major categories of patients, such as those with coronary disease, diabetes, or hypertension, as well as patients older than 70 years of age, and those with initially elevated lipid levels.

Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20 536 people with cerebrovascular disease or other high-risk conditions. Heart Protection Study Collaborative Group. Lancet. March 6, 2004;363:757–67.



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