Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) have been shown to significantly benefit adult patients in the primary and secondary prevention of cardiovascular and cerebrovascular events. The impact that the medications have on elderly patients is less clear, and it even has been suggested that lowering cholesterol levels could put elderly patients at increased risk of mortality. Shepherd and colleagues studied 5,804 elderly persons at risk of cardiovascular or cerebrovascular events to ascertain the effect of statin therapy.
The investigators recruited 2,804 men and 3,000 women 70 to 82 years of age from several centers in Scotland, Ireland, and the Netherlands. All participants either had confirmed cerebrovascular or cardiovascular disease or were at significant risk of these conditions because of smoking, hypertension, or diabetes. After completing a battery of physical and psychologic screening tests, all patients participated in a four-week placebo period to assess compliance. Patients who used less than 75 percent or more than 120 percent of the prescribed placebo medication were excluded from the study. The remaining patients were randomly assigned to treatment with 40 mg per day of pravastatin (2,891 patients) or placebo (2,913 patients) and were evaluated every three months.
The primary outcome of interest was the combined total of definite or suspected deaths from a cardiac cause, nonfatal myocardial infarction, and any stroke. All cerebrovascular and cardiovascular events in the participants were monitored, as were assessments of disability and cognitive function and changes in baseline risk factors such as smoking, diabetes, hypertension, and lipid status.
The groups were comparable at the time of randomization. The average age of participants was 75 years, and 48 percent were men.
About 27 percent were smokers, 11 percent had diabetes, more than 60 percent had hypertension, and more than 25 percent had a history of angina. After three months, the levels of low-density lipoprotein (LDL) cholesterol were 34 percent lower, the levels of high-density lipoprotein cholesterol were 5 percent higher, and the triglyceride levels were 13 percent lower in compliant patients in the treated group. By the second year, reduction in LDL cholesterol levels was 33 percent. The overall risk of a primary end point was 15 percent lower in patients receiving pravastatin. This was caused by a 19 percent reduction in coronary events with no discernible reduction in cerebrovascular events.
In the treated group, transient ischemic attacks (TIAs) were reduced by 25 percent and death from coronary heart disease by 24 percent. The groups did not differ significantly in rates of overall mortality, hospital admission, or revascularization procedures. The greatest reduction in risk was in men and in secondary rather than primary prevention. About 55 percent of patients in both groups reported one or more serious adverse effects, but there was no excess of myalgia among patients in the treatment group. New cancers were more common in the treatment group (245 patients) than in the placebo group (199 patients).
The authors conclude that in elderly patients at risk of cardiovascular disease, treatment with pravastatin was associated with a 15 percent relative reduction in combined cardiovascular and cerebrovascular end points after three years. Although the benefit was observed primarily in cardiovascular events, the impressive reduction in TIAs indicates a protective effect on cerebrovascular function. Patients tolerated the medication well, and there was little evidence of adverse metabolic effect, even in patients taking multiple other medications.