PROspective Study Of Pravastatin Research Articles

Plasma lipoprotein(a) [Lp(a)] concentrations and cardiovascular events in the elderly: evidence from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Using analyses of the large cohort ( n = 5732) from the prospective study of pravastatin in the elderly at risk (PROSPER), we tested the hypothesis that Lp(a) concentration is an independent predictor of major vascular events and cognitive impairment in the elderly. Baseline Lp(a) levels were measured on fresh samples from 5732 subjects aged 70–82, who were followed for 3.2 years on average. Lp(a) levels were not significantly different across the age range in PROSPER, but were significantly higher in women (geometric mean 14.8 versus 12.4 mg/dl, P < 0.0001). Those with a history of vascular disease had significantly higher Lp(a) levels, which remained after adjustment ( P < 0.0001). There was no statistically significant association between baseline Lp(a) and the risk of the primary endpoint (CHD death, non-fatal MI and fatal or non-fatal stroke) (hazard ratio 1.05, 95% CI 1.00–1.11, P = 0.077), but after adjustment for baseline risk factors this did achieve statistical significance (1.06, 1.005–1.12, P = 0.032). Finally, there was no statistically or clinically significant association between any adjusted baseline or dynamic cognition variables and Lp(a), and nor was there any significant association between Lp(a) and indices of disability throughout the study. This is the first study of the association between Lp(a) and a range of cardiovascular endpoints including cognitive and disability indices in the elderly. The main finding is that Lp(a) level, while influenced by a number of baseline characteristics, is not a significant predictor of cognitive function or levels of disability, but is a predictor of combined cardiovascular events over an average 3.2 year follow-up.

Closing out a large clinical trial: lessons from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Relatively little has been written about the practicalities of the closeout of large, multi-centre clinical trials, but this aspect of trial conduct and design is both important and requires careful planning in order to be accomplished in a timely and orderly fashion. Here, we document our recent experiences of closing down the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). This five-year study with over 5800 subjects was closed down and published in 2002. We describe the methods used to ensure the speedy progression from the start of the closeout period through data lock to publication and presentation of the results. We discuss the strategic planning of all aspects of the closeout process, the training of staff for final visits, the methods used to follow-up all study participants including those used in dealing with "difficult to contact" and defaulted patients, and the strategies employed to ensure that study participants were left with positive feelings about the study. We also detail the methods employed to expedite the throughput of study paperwork and endpoints and the cleaning of data in preparation for data lock and subsequent publication and presentation of the results. Based on our experiences we summarize the most important aspects of closeout design and make recommendations for future studies, the most important of which is that a well-planned and well-managed closeout is a key feature of any large scale clinical trial and a coherent and practicable closeout strategy should be an integral part of the design.

Statin therapy in the elderly.

The clinical efficacy and safety of statin therapy have been well established from a series of large-scale, randomized controlled trials. These trials, however, have predominantly recruited patients under the age of 70 years. As a consequence, the use of statins in older patients has remained controversial. The results of the first trial to look exclusively at the elderly--the Prospective Study of Pravastatin in the Elderly at Risk--have added enormously to our understanding of the use of statins in the elderly. These findings, together with those from the large elderly cohort within the Heart Protection Study and the smaller elderly subgroups within the other major statin trials, have forced us to re-evaluate any systematic exclusion of elderly patients from statin therapy. The collective evidence now strongly supports the use of statins in the at-risk elderly population.

Understanding why older people participate in clinical trials: the experience of the Scottish PROSPER participants

over the next 20 years it is anticipated that there will be a significant increase in those aged 75 and over, and a consequent increase in cardiovascular disease, cancer and chronic illness. As this shift takes effect, there will be an increased need for treatment strategies that are of known benefit to this age group and a consequent rise in demand for clinical trials that are conducted specifically with the older population. Because factors that motivate older individuals to participate in clinical trials may differ from those that influence younger adults, it is important to evaluate the strategies used to encourage recruitment and retention and to determine how appropriate these are. evaluation of the reasons why subjects agree to participate in a controlled clinical trial of vascular disease prevention and the strategies used to improve compliance and protocol adherence. Scotland. 2,520 Prospective Study of Pravastatin in the Elderly at Risk participants, aged 70-82 with either pre-existing vascular disease or at least one major vascular risk factor (hypertension, cigarette smoking, or diabetes mellitus). two-stage iterative survey. Stage I was exploratory. curiosity, or an interest in finding out more about the study, 'a desire to support research', and anticipated personal benefits, such as health screening, were the most important motivators for generating initial interest in the trial. Ongoing health monitoring was the most important recruitment and retention motivator (P = 0.001). curiosity, self interest and altruism may act as motivators at different points in the study time-line. However, fostering positive relationships between staff and recruits, and keeping recruits informed about the progress of the study are likely to maximise the retention of older subjects to long-term trials.

Preventing the next event in the elderly: the PROSPER perspective.

Statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals but their efficacy and safety in elderly people has not been confirmed. Several clinical trials including the Cholesterol and Recurrent Events (CARE) and Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), have sub-analysed their results for the 'elderly' cohort, but the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial is the first trial to specifically evaluate the benefits of statin therapy on vascular risk in elderly men and women. The results have shown that pravastatin, given for 3 years, reduced the risk of coronary heart disease in elderly individuals. Within this same time frame, there was no significant benefit on the risk reduction of stroke but there was a trend to reduce the risk of transient ischemic attacks. It was discovered that those patients with the lowest baseline high-density lipoprotein cholesterol gained the most benefit from the intervention. Drug interactions between pravastatin and the concomitant medications seen in this elderly cohort, was not a significant clinical issue. Therefore, PROSPER extends to elderly individuals the treatment strategy currently used in middle-aged people.

Pravastatin: a review of its use in elderly patients.

Pravastatin (Pravachol) is a competitive, reversible HMG-CoA reductase inhibitor that lowers serum cholesterol levels by inhibiting de novo cholesterol synthesis and has antiatherogenic effects that appear to be partially independent of its lipid-lowering effects. Pravastatin 10-40 mg/day produced significant reductions (vs baseline or placebo) in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in elderly patients (aged >or=60 or >or= 65 years) with hypercholesterolaemia or normal cholesterol levels. Serum triglyceride and high-density lipoprotein cholesterol levels also improved in some studies, but not in others. Coadministration of cholestyramine, another lipid-lowering agent, further enhanced the lipid-lowering effects of pravastatin in elderly patients. Data from the large, long-term (3-6 years) PROspective Study Of Pravastatin in the Elderly at Risk (PROSPER), Cholesterol And Recurrent Events trial (CARE) and Long term Intervention with Pravastatin in Ischaemic Disease (LIPID) trials demonstrated that pravastatin 40 mg/day reduces coronary events in elderly patients with hypercholesterolaemia or normal cholesterol levels, with or at high risk of developing coronary heart disease (CHD). In these trials, the incidence of death from CHD or the combined endpoint of death from CHD or nonfatal myocardial infarction was significantly lower in pravastatin than in placebo recipients. Pravastatin is well tolerated in the elderly, and adverse effects considered related to therapy are minimal. The most commonly occurring adverse events included gastrointestinal events, renal or genital system events, respiratory disorders, headaches and musculoskeletal pain. Pravastatin effectively lowers serum TC and LDL-C levels and, as demonstrated in major clinical outcome trials, reduces coronary events in elderly patients with hypercholesterolaemia or normal cholesterol levels. Pravastatin is well tolerated and as such should be considered a first-line agents for primary or secondary prevention in older individuals with evident CHD or multiple risk factors for CHD.

Measuring the cost-effectiveness of lipid-lowering drugs in the elderly:: the outcomes research and economic analysis components of the PROSPER trial

Little information exists to quantify the functional status and economic consequences of lipid-lowering therapy in elderly patients. We describe the design of the cost-effectiveness component of the first large, randomized, placebo-controlled trial of lipid-lowering therapy in subjects aged 70 years or older. The PROspective Study of Pravastatin in the Elderly at Risk has randomized 5804 men and women 70–82 years old, with existing vascular disease or related risk factors, to receive 40 mg/d of pravastatin or placebo. The cost-effectiveness study will be based on within-trial observations of differences between the two study arms in rates of myocardial infarction, stroke and related vascular disease outcomes (including vascular dementia). In addition to comparing within-trial clinical outcomes, we will model the projected changes in life expectancy and cardiovascular outcome rates that would be seen with lifelong use of the drug, based on the risk reduction rates seen in the trial as well as baseline observational data from the three countries where the trial is being conducted (Scotland, Ireland and the Netherlands). A state transition (Markov) model will be constructed to estimate the likely states of health, functional status and health care resource utilization (including lipid-lowering drug costs) in a cohort of elderly patients with versus without pravastatin therapy over a series of 1-year cycles until death. In addition, a standard measure of utility (the Health Utilities Index) will be administered to all study subjects to permit calculation of quality-adjusted life-years gained with this regimen. This approach will make it possible to go beyond the calculation of a single endpoint for each subject, and to translate the trial findings into definitions of effectiveness and outcomes that will be relevant to the ongoing debate concerning how best to relate the benefits of such medications to their costs.

Testing cognitive function in elderly populations: the PROSPER study

Objectives: For large scale follow up studies with non-demented patients in which cognition is an endpoint, there is a need for short, inexpensive, sensitive, and reliable neuropsychological tests that are...

A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics.

BackgroundPROSPER was designed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option.MethodsThe PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomised, double blind, placebo-controlled trial to test the hypothesis that treatment with pravastatin (40 mg/day) will reduce the risk of coronary heart disease death, non-fatal myocardial infarction, and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition.ResultsIn Scotland, Ireland, and the Netherlands, 23,770 individuals were screened, and 5,804 subjects (2,804 men and 3,000 women), aged 70 to 82 years (average 75 years) and with baseline cholesterol 4.0–9.0 mmol/l, were randomised. Randomised subjects had similar distributions with respect to age, blood pressure, and body mass index when compared to the entire group of screenees, but had a higher prevalence of smoking, diabetes, hypertension, and a history of vascular disease. The average total cholesterol level at baseline was 5.4 mmol/l (men) and 6.0 mmol/l (women).ConclusionsCompared with previous prevention trials of cholesterol-lowering drugs, the PROSPER cohort is significantly older and for the first time includes a majority of women. The study, having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women, aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002.

Apolipoprotein (a) isoform size is not the only determinant of plasma lipoprotein(a) level in the elderly: Data from the prospective study of pravastatin in the elderly at risk: PROSPER Allan Gaw, Elizabeth A. Brown, John Norrie, PROSPER Executive. Glasgow Royal Infirmary, Glasgow, United Kingdom, University of Glasgow, Glasgow, United Kingdom

Apolipoprotein (a) isoform size is not the only determinant of plasma lipoprotein(a) level in the elderly: Data from the prospective study of pravastatin in the elderly at risk: PROSPER Allan Gaw, Elizabeth A. Brown, John Norrie, PROSPER Executive. Glasgow Royal Infirmary, Glasgow, United Kingdom, University of Glasgow, Glasgow, United Kingdom

Prospective study of pravastatin in the elderly at risk: Vascular risk profile of the prosper recruits

Prospective study of pravastatin in the elderly at risk: Vascular risk profile of the prosper recruits

Baseline lipid and lipoprotein concentrations in the participants of the prospective study of pravastatin in the elderly at risk (prosper)

Baseline lipid and lipoprotein concentrations in the participants of the prospective study of pravastatin in the elderly at risk (prosper)

The prosper design. A prospective study of pravastatin in the elderly at risk

The prosper design. A prospective study of pravastatin in the elderly at risk

The prosper rationale. A prospective study of pravastatin in the elderly at risk

The prosper rationale. A prospective study of pravastatin in the elderly at risk