ArticlesPravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial
Introduction
Findings of clinical trials1–6 of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have shown significant benefits in both primary and secondary prevention of coronary and cerebrovascular disease events. Most of this evidence comes from studies done on middle-aged men. The rationale for such treatment in people older than age 70 years, most of whom die of vascular disease, is less clear because the association between plasma cholesterol and risk of coronary artery disease diminishes with increasing age.7, 9 The frequency of stroke, an important manifestation of vascular disease in elderly individuals, is associated with hypertension and seems independent of plasma cholesterol.10 However, investigators of previous statin trials11 have reported benefits on stroke, and results of observational studies have raised the possibility that statins could reduce the rate of cognitive decline in elderly people.12 However, in the oldest old people, low plasma cholesterol is associated with increased mortality.8, 9 In view of these conflicting observations, we concluded that the balance of the efficacy and safety of cholesterol lowering in older people had yet to be established, and we launched the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Our aim was to ascertain if treatment with pravastatin reduces the risk of cardiac events, stroke, cognitive decline, and disability in those with existing (secondary prevention) and in those at high risk of developing (primary prevention) vascular disease.13, 14, 15 We chose a treatment period of a minimum of 3 years as a reasonable time frame to test the efficacy of the medication in what for many individuals is the last decade of their life.
Section snippets
Methods
The protocol of PROSPER has been published elsewhere.13
Results
Figure 1 shows the trial profile, and table 1 the baseline characteristics of participants. 23 770 men and women were screened, and 5804 randomly assigned to pravastatin or placebo (2520 from Scotland, 2184 from Ireland, and 1100 from the Netherlands). The groups were balanced with respect to all relevant characteristics (table 1).
Mean follow-up was 3·2 years (range 2·8–4·0) for participants who did not die or withdraw consent. The proportion of potential visits to trial centres actually
Discussion
Treatment of elderly individuals for 3 years with pravastatin produced a 15% relative reduction (2·1% absolute reduction) in the risk of the primary endpoint in PROSPER. Over this period, individuals on pravastatin had less coronary events than those on placebo, but rates of stroke remained the same. However, an apparent reduction in transient ischaemic attacks suggests that the treatment did have an effect on the cerebrovascular circulation. Caution should be taken in interpretation of these
References (29)
- et al.
Total cholesterol and risk of mortality in the oldest old
Lancet
(1997) - et al.
Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study
Lancet
(2001) - et al.
Statins and the risk of dementia
Lancet
(2000) - et al.
The design of a prospective study of pravastatin in the elderly at risk (PROSPER)
Am J Cardiol
(1999) - et al.
Automated serial EGG comparison based on the Minnesota Code
J Electrocardiol
(1996) - et al.
Beta blockade during and after myocardial infarction: an overview of the randomized trials
Prog Card Dis
(1985) - et al.
Effect of simvastatin on ischemic signs and symptoms in the Scandinavian Simvastatin Survival Study
Am J Cardiol
(1998) - et al.
Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study
Lancet
(1997) - et al.
Do statins cause cancer? A Meta-analysis of large randomised clinical trials
Am J Med
(2001) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
Lancet
(1994)
Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia
N EnglJ Med
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels
N Engl J Med
Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS Airforce/Texas Coronary Atherosclerosis Prevention Study
JAMA
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels
N Engl J Med
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