Effects of fluvastatin on cardiac events in renal transplant patients: ALERT (Assessment of Lescol in Renal Transplantation) study design and baseline data.

BACKGROUND: Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins') reduces morbidity and mortality from coronary heart disease in diverse patient populations. STUDY AIMS: The aim of the present ALERT (Assessment of Lescol in Renal Transplantation) study is to determine whether renal transplant recipients would also benefit from statin therapy. ALERT is a multicentre, randomized, double-blind, placebo-controlled trial to assess the effect of fluvastatin in renal transplant recipients with mild-to-moderate hypercholesterolaemia. The primary objective is to investigate the effects of fluvastatin on major adverse cardiac events (MACE). In addition, the effects on cardiovascular and all-cause mortality, as well as renal function, will be addressed. STUDY POPULATION: The study population contains patients with functioning renal allografts of more than 6 months' duration, recruited from 75 centres in Northern Europe and Canada. Patients of both sexes, aged 30-75 years, with a total cholesterol level of 4.0-9.0 mmol/l (155-348 mg/dl) were included, except for those with a history of myocardial infarction, where the upper limit for inclusion was 7.0 mmol/l (270 mg/dl). STUDY DESIGN: A total of 2100 patients were recruited by the end of October 1997 and will be followed for up to 6 years. This report presents the design features of the study (recruitment, follow-up, sample size, data analysis and study organization), along with baseline results. ALERT is the first large-scale prospective, randomized, double-blind study to address the prevention of cardiovascular mortality in renal transplant patients receiving an HMGCoA reductase inhibitor.

Cost effectiveness of simvastatin treatment to lower cholesterol levels in patients with coronary heart disease. Scandinavian Simvastatin Survival Study Group.

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) showed that lowering cholesterol levels with simvastatin reduces mortality and morbidity in patients with angina pectoris or previous acute myocardial infarction. Before the widespread use of cholesterol-lowering drugs in such patients is recommended, its cost effectiveness should be demonstrated. We estimated the cost effectiveness of simvastatin treatment to lower cholesterol levels in relation to the age, sex, and cholesterol level before treatment of patients with coronary heart disease. METHODS: We estimated the cost per year of life gained with simvastatin therapy. To model the increased life expectancy, hazard functions from 4S were used. The costs studied included those of the intervention and the direct and indirect costs associated with morbidity from coronary causes. We prepared separate estimates for men and women at various ages (from 35 to 70 years) and total cholesterol levels before treatment (213 to 309 mg per deciliter). RESULTS: In the analysis limited to direct costs, the cost of each year of life gained ranged from $3,800 for 70-year-old men with 309 mg of cholesterol per deciliter to $27,400 for 35-year-old women with 213 mg of cholesterol per deciliter. When we included indirect costs, the results ranged from a savings in the youngest patients to a cost of $13,300 per year of life gained in 70-year-old women with 213 mg of cholesterol per deciliter. CONCLUSIONS: In patients with coronary heart disease, simvastatin therapy is cost effective among both men and women at the ages and cholesterol levels studied.

Cost-effectiveness of cholesterol lowering. Results from the Scandinavian Simvastatin Survival Study (4S)

An analysis of the cost-effectiveness of simvastatin was conducted, based on the Scandinavian Simvastatin Survival Study (4S). The total cost of hospitalization in the placebo group was 52.8 million Swedish kronor (SEK) (5.15 million pounds), compared with SEK 36.0 million (3.51 million pounds) in the simvastatin group. This amounts to a 32% reduction, or a saving of SEK 16.8 million (1.6 million pounds) or SEK 7560 (738 pounds) per patient. The net cost per patient for the duration of the study (5.4 years) was SEK 13,540 (1324 pounds). Simvastatin treatment saved an estimated 0.377 undiscounted life years (0.240 life years discounted at 5% per annum). The cost of simvastatin therapy per discounted life-year saved was therefore SEK 56,400 (5502 pounds). Sensitivity analysis, examining the effect of different life expectancies, costs of initiation and monitoring of simvastatin therapy, and discount rates, showed the results to be stable. Conclusion. The cost per life-year saved of simvastatin in the treatment of post-myocardial infarction and angina patients, as determined from 4S data, is well within the range normally considered cost-effective.

Cholesterol lowering and the use of healthcare resources. Results of the Scandinavian Simvastatin Survival Study.

BACKGROUND: Advances in the treatment of cardiovascular disease have increased costs; annual cardiovascular healthcare expenditure in the United States currently exceeds $100 billion. Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study is a randomized, double-blind, placebo-controlled trial in which simvastatin reduced the risk of death by 30% (P=.0003) over the median follow-up period of 5.4 years in patients with previous myocardial infarction or stable angina pectoris as a result of a 42% reduction in the risk of coronary deaths (P=.00001). In the present report, data prospectively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare resource use and perform a cost-minimization analysis. In the placebo group (n=2223), there were 1905 hospitalizations (average duration, 7.9 days) for acute cardiovascular events or coronary revascularization procedures among 937 patients, whereas in the simvastatin group (n=2221), there were 1403 such hospitalizations (average duration, 7.1 days) among 720 patients (all differences, P<.0001). The corresponding number of hospital days was 15089 and 9951 in the two groups, respectively (34% reduction,P<.0001). In the United States, the resulting reduction in hospitalization costs over the 5.4 years of the trial would be $3872 per patient, reducing the effective cost of simvastatin by 88% to $0.28 per day. CONCLUSIONS: In addition to reducing mortality and morbidity in coronary heart disease patients, simvastatin markedly reduces use of hospital services, thus offsetting most of its cost.

Reproducibility of quantitative arteriographic assessment of atherosclerosis in the femoral artery.

Results from computer-analysed angiograms in the Probucol Quantitative Regression Swedish Trial (PQRST) were analysed to determine the reproducibility of the method and any drift in the analysing system. The precision index (P(mu)) for 2 angiography series, made at 10 min intervals, of the femoral artery in 276 patients was 10.5 for lumen volume and 21.9 for roughness (edge irregularity). No difference in reproducibility was found between patients with and without symptoms of peripheral atherosclerosis or when looking at the reproducibility over years. A drift of 0.67% per year in the radiographic equipment (but not in the analysis system) was found, confirmed by use of phantoms. Computer-based analysis of femoral atherosclerosis is a reliable method for follow-up trials, giving high reproducibility even if the trial spans over several years and involves different centres. The use of phantoms is essential for checking the method over time.