Prospective Study of Pravastatin in the Elderly at Risk - PROSPER

Description:

Randomized trial of pravastatin for reduction of clinical events in high-risk elderly patients.

Hypothesis:

Use of pravastatin will reduce the composite endpoint of cardiovascular death, nonfatal myocardial infarction (MI) and fatal or nonfatal stroke in high-risk elderly patients compared with placebo.

Study Design

Patients Screened: 23,770
Patients Enrolled: 5,804
Mean Follow Up: 2.8 years-4.0 years (mean 3.2 years)
Mean Patient Age: 70-82 years
Female: 52

Patient Populations:

Age 70-82 years; pre-existing vascular disease (coronary, cerebral, or peripheral) or raised risk of such disease (smoking, hypertension, or diabetes); plasma total cholesterol 4.0-9.0 mmol/L; triglyceride <6.0 mmol/L

Exclusions:

Poor cognitive function

Primary Endpoints:

Composite of cardiovascular death, nonfatal MI, and fatal or nonfatal stroke.

Secondary Endpoints:

Individual components of primary composite endpoint (cardiovascular death, nonfatal MI, and fatal or nonfatal stroke); primary endpoint analysis stratified by gender and by pre-existing disease.

Drug/Procedures Used:

Pravastatin 40 mg daily (n=2,891) compared with placebo (n=2,913).

Principal Findings:

At 3 months, patients in the pravastatin arm had a 34.0% reduction in LDL, 23.4% reduction in total cholesterol, 4.9% increase in HDL and 13.3% decrease in triglycerides. The primary endpoint of cardiovascular (CV) death, nonfatal MI and fatal or nonfatal stroke at 3.2 years was reduced in the pravastatin arm relative to the placebo arm (14.1% vs 16.2%, hazard ratio = 0.85, p=0.014). The secondary endpoint of CV death or MI was also lower in the prvastatin arm (10.1% vs 12.2%, HR=0.81, p=0.006), as was CV death alone (3.3% vs 4.2%, HR=0.76, p=0.043). There was no difference in the rate of stroke (4.7% vs 4.5%, p=0.81). There was no treatment effect with regard to heart failure requiring rehospitalization, revascularization, cognitive function, or disability. The safety endpoint of new cancer was significantly higher in the pravastatin arm (8.5% vs 6.8%, HR 1.25, 95% CI 1.04, 1.51, p=0.020). However, in a meta-analysis of statin randomized placebo-controlled trials, treatment with either pravastatin (HR 1.06, p=0.20) or any statin (HR 1.02, p=0.32) was not associated with an excess risk of cancer.

Interpretation:

The PROSPER trial was the first major study to look at use of a lipid-lowering agent specifically in high-risk elderly patients. The age range was 70-82 years, and more than half of the patients were at high risk for vascular disease. The composite endpoint and all components of the endpoint except stroke showed a benefit of pravastatin use in this population. The major safety concern was the increased rate of cancer in the pravastatin arm; however, this was not confirmed in a meta-analysis. Further exploration into the relation of the therapy to an increased cancer rate in the elderly may be warranted. Many prior trials have shown a benefit for primary and secondary prevention of coronary and cerebrovascular disease events with statin use (LIPID, 4S, AFCAPS, HPS), although the majority of the patients enrolled in these trials were middle-aged men. Results of the PROSPER trial now suggest that statin use for vascular risk management should also be applied to elderly patients.

References:

Lancet 2002; 360: 1623–30.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Hypertension, Smoking

Keywords: Stroke, Cognition, Neoplasms, Myocardial Infarction, Coronary Artery Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Smoking, Risk Management, Cholesterol, Heart Failure, Pravastatin, Triglycerides, Hypertension, Diabetes Mellitus


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