The Prospective Study of Pravastatin in the Elderly at Risk: The Results of PROSPER

James Shepherd, MD
University of Glasgow
Glasgow, UK


3 years of pravastatin treatment reduced risk of coronary disease in the elderly. This finding suggests that clinicians should not hesitate to extend statin treatment beyond middle-aged persons to older individuals.

Currently, there are approximately 150 million individuals worldwide aged 65 or older. This group is expected to swell to 300 million within 30 years. Accordingly, physicians can expect to see a substantial increase in the number of heart attacks, strokes, disability, dependence on society, and dementia.

One of the most pressing questions in statin trials is the effect on the elderly. Statins clearly reduce morbidity and mortality in middle-aged individuals. However, their efficacy and safety is not fully established in older patients.

The PROSPER study (PROspective Study of Pravastatin in the Elderly at Risk) was an international trial including one center each in Scotland, Ireland and the Netherlands. Investigators designed this study to determine whether they could reduce vascular risk in the elderly using statin therapy.

Researchers recruited 5,804 individuals, including 3,000 women and 2,804 men, between the ages of 70 and 82 years. They randomized the patients to receive either pravastatin 40 mg/day or placebo.

Approximately one-half of the patients had existing vascular disease, and the other half were at very high risk of vascular disease because of risk factors including diabetes, hypertension or smoking. All individuals had good cognitive function at beginning of trial.

Because of the advanced age of the trial subjects, investigators agreed to limit the trial length to no more than 3.5 years of follow-up. By comparison, most large, randomized statin trials follow patients for 5 years or longer. Therefore, PROSPER investigators did not expect to see a mortality benefit. Instead, they chose to evaluate the ability of statins to reduce morbidity. The primary endpoint of the trial combined incidence of coronary death, myocardial infarction and stroke (fatal or non-fatal).

In addition to lowering LDL cholesterol by 34%, pravastatin lowered the composite primary endpoint of vascular events by 15%. There were 408 events in the pravastatin group, compared with 437 in the placebo group (p = 0.014). Dr. Shepherd said they would need to treat 48 individuals to prevent one coronary death, myocardial infarction or stroke.

The greatest benefit was seen in coronary vessels. There was a 19% reduction in fatal and non-fatal myocardial infarction, and a 24% reduction in deaths from coronary heart disease alone.

Previous statin trials showed it is possible to prevent stroke with statin treatment. However, this benefit did not appear until after 5 or more years of treatment. The PROSPER trial, which included a mean of 3.2 years of patient follow-up, showed no effect on stroke risk. This suggests that it is not possible to prevent stroke in a short treatment period in individuals who are at higher risk of such events.

Because there was no benefit in reduction of stroke, investigators felt it would be unlikely to see an improvement in cognitive function. In fact, treatment with pravastatin did not attenuate or accelerate the progressive decline of cognitive function that occurs in old age.

Safety analysis showed that adding pravastatin to other drugs did not increase the risk of side effects. Patients, on average, were taking 3.6 different drugs per day, and as many as 16 per day. Despite that, there was no increase in risk of myopathy, no reports of rhabdomyalysis, and no increase in liver function abnormalities.

Consequently, Dr. Shepherd and colleagues believe PROSPER is good news for the elderly. The study results show that statin treatment as currently applied to middle aged individuals is equally applicable to older persons.


Reporter: Andrew Bowser