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Treatment with Pravastatin and Risk of Stroke



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Am Fam Physician. 2001 Feb 15;63(4):752-754.

Cerebrovascular accidents are the second leading cause of death worldwide. A direct correlation between elevated cholesterol levels and coronary artery disease has been well established. However, studies have not consistently shown a similar relationship between lipid levels and stroke. In one large study, a relationship with ischemic stroke was found, but an increase in intracerebral hemorrhage was also noted. Several trials that studied gemfibrozil, niacin or diet to lower cholesterol levels found no reduction in the rate of stroke. At least four small studies that used a 3-hydroxy-3-methylglutaryl-coen-zyme A reductase inhibitor reported a reduction of 25 to 30 percent in the overall rate of stroke. White and colleagues recently reported additional results of the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study.

Patients were enrolled over a period of 30 months. All study participants had a history of myocardial infarction or unstable angina pectoris during the previous three to 36 months. A total cholesterol level of 155 to 271 mg per dL (4.00 to 7.00 mmol per L) was required for enrollment, and the triglyceride level could not be greater than 445 mg per dL (5.02 mmol per L). Patients underwent double-blind randomization to receive placebo or 40 mg of pravastatin daily. The primary end point of the study was death, with the secondary end point being stroke from any cause (total strokes), including hemorrhagic and nonhemorrhagic stroke. A diagnosis of either type of stroke was based on previously established clinical criteria as well as the results of computed tomographic scans or magnetic resonance imaging.

A total of 9,014 patients was enrolled in the study, with 4,512 randomized to the pravastatin group and 4,502 to the placebo group. The median age of the patients was 62 years, and 83 percent were men. Eighty-two percent were already taking aspirin, and 4 percent had a previous history of stroke. During the six years of follow-up, the treatment group had a mean decline in total cholesterol level from 218 to 179 mg per dL (5.65 to 4.60 mmol per L), which was 18 percent greater than the reduction in the placebo group. The treatment group also had a mean decline in low-density lipoprotein (LDL) cholesterol of 27 percent, 25 percent more than the placebo group.

A total of 419 strokes was confirmed, of which 231 occurred in patients in the placebo group and 188 in those who took pravastatin. This translates to a relative risk reduction of 19 percent and eight fewer stokes for every 1,000 patients treated with pravastatin for six years (see accompanying table). The rates of hemorrhagic stroke did not differ significantly between the treatment and placebo groups. After readjusting the data for a variety of baseline characteristics, including older age, systolic blood pressure, diabetes, current smoking, history of stroke or atrial fibrillation, the study found a 16 percent reduction in overall risk of stroke and a 21 percent reduction in the risk of nonhemorrhagic stroke. The rates of mortality following stroke, 13.0 percent in the pravastatin group and 13.2 percent in the placebo group, did not differ significantly.

Risk Ratios for Stroke

FIGURE.

Risk ratios for stroke from any cause (total stroke) and various types of stroke, according to study group. The horizontal lines indicate 95 percent confidence intervals. The scale for risk ratios is logarithmic. Because of rounding, values for subcategories do not necessarily sum to the category totals.

Reprinted with permission from White HD, Simes J, Anderson NE, Hankey GJ, Watson JD, Hunt D, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000;343:321.

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Risk Ratios for Stroke


FIGURE.

Risk ratios for stroke from any cause (total stroke) and various types of stroke, according to study group. The horizontal lines indicate 95 percent confidence intervals. The scale for risk ratios is logarithmic. Because of rounding, values for subcategories do not necessarily sum to the category totals.

Reprinted with permission from White HD, Simes J, Anderson NE, Hankey GJ, Watson JD, Hunt D, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000;343:321.

Risk Ratios for Stroke


FIGURE.

Risk ratios for stroke from any cause (total stroke) and various types of stroke, according to study group. The horizontal lines indicate 95 percent confidence intervals. The scale for risk ratios is logarithmic. Because of rounding, values for subcategories do not necessarily sum to the category totals.

Reprinted with permission from White HD, Simes J, Anderson NE, Hankey GJ, Watson JD, Hunt D, et al. Pravastatin therapy and the risk of stroke. N Engl J Med 2000;343:321.

The authors conclude that pravastatin provides a modest benefit in prevention of stroke among patients with known coronary artery disease. Treatment did not make a difference in rates of mortality related to stroke. However, the study did find a 24 percent relative reduction in the risk of death related to coronary artery disease and a 22 percent relative risk reduction in death from all causes, which were the primary end points of the first part of this trial.

White HD, et al. Pravastatin therapy and the risk of stroke. N Engl J Med. August 3, 2000;343:317–26.



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