Statins for Stroke Prevention in the Elderly: No Closer to the Truth

While investigating the benefits of statin therapy in the seldom studied elderly, the PROSPER study found that pravastatin reduced the risk of coronary disease as it has in studies of middle-aged people, yet unlike previous studies, did not have a clear effect on risk of stroke.

The benefits of statins have been demonstrated for the primary and secondary prevention of both coronary and cerebrovascular events, but most of this evidence has involved middle-aged people. The rationale for such treatment in those older than 70 years is less clear, since the association between cholesterol levels and risk of coronary artery disease diminishes with increasing age, and the frequency of stroke is associated with hypertension rather than with cholesterol. However, there has been enough conflicting evidence to challenge these concepts such that investigators launched the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) to look more closely at the efficacy of statin therapy in older people. The researchers set out to determine whether pravastatin reduces the risk of cardiac events, stroke, cognitive decline and disability in those with existing (secondary prevention) and those at high risk of developing (primary prevention) vascular disease.

A total of 5,804 men and women 70-82 years old were recruited if they had pre-existing vascular disease or a high risk of developing vascular disease due to smoking, hypertension or diabetes. Of these, 2,891 were randomized to treatment with pravastatin 40mg per day and 2,913 to placebo. Plasma total cholesterol levels had to be 4.0-9.0mmol/L and their triglyceride concentration less than 6.0mmol/L. Every three months, lipoprotein profiles were measured, and every year an electrocardiogram was recorded and cognitive function tests and disability assessments were performed. Follow-up was 3.2 years on average and the primary outcome was the combined endpoint of definite or suspect death from coronary heart disease, non-fatal myocardial infarction and fatal or non-fatal stroke. Secondary outcome was a separate examination of coronary and cerebrovascular components, while tertiary outcomes included disability and cognitive function.

Pravastatin was found to reduce the risk of the primary endpoint by 15% (relative reduction; p=0.014), yet this risk reduction was largely attributable to a reduction in risk of coronary events only. Upon separation, investigators noted a 19% reduction in coronary events (p=0.006) but no discernable effect on cerebrovascular events (p=0.81). Reductions, although non-significant, were found in transient ischemic attacks and the frequency of revascularization procedures among participants taking pravastatin. There were no observed differences between treatment and placebo groups in all-cause mortality or rates of hospital admissions for heart failure. Furthermore, serious adverse events were reported with similar frequency in both groups, and cognitive function declined at the same rate.

The overall reduction in the primary endpoint in pravastatin-treated subjects was less than predicted because of the lack of effect on rates of stroke. This finding was not, however, due to pravastatin's inability to lower low-density lipoprotein (LDL) cholesterol; at three months LDL cholesterol was 34% lower in treated subjects and after two years remained 33% lower than levels measured in placebo subjects. Researchers propose that the lack of effect on stroke might be due to a lack of statistical power, or may be a consequence of the short duration of the trial since other research suggests that stroke benefit from statin therapy does not begin to appear until after three years (whereas coronary risk reduction is an early event).

Extrapolating results from the PROSPER study to clinical practice is difficult. Although it provides clear evidence that statin therapy in elderly individuals reduces the risk of coronary disease, as it does in middle-aged people, a clear result on stroke would require a longer period of treatment if indeed statins are even beneficial for this indication in the elderly.


  1. Shepherd J, Blavw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-30.