Because of the potential for large variability among countries in the utilization and cost of health care resources, it is important to assess the appropriateness of combining economic data across the countries in a multinational clinical economic trial. We show how available tests for interaction can be applied to economic endpoints, including cost-effectiveness ratios and net health benefits. This analysis includes a characterization of possible interactions being quantitative or qualitative in nature. In the absence of interaction, a pooled estimate of the economic endpoint should be representative of the participating countries. We explore the analytic issues by further analysing data from the Scandinavian Simvastatin Survival Study (4S).
The purpose of this study was to evaluate the hypothesis that high serum levels of ADMA, an indicator of endothelial dysfunction, are associated with an elevated risk of acute coronary events in middle-aged men. To test the hypothesis that lipid lowering medication with statins lowers circulating ADMA levels, we also investigated the effect of simvastatin and atorvastatin treatment on plasma ADMA concentration. In a prospective nested case-control study in 150 middle-aged non-smoking men from Eastern Finland, those who were in the highest quartile for serum ADMA (>0.62 micromol/l) had a 3.9-fold (95% CI: 1.25-12.3, P=0.02) increase in risk of acute coronary events compared with other quartiles. In an 8-week randomised double-blind placebo-controlled trial, plasma ADMA concentrations remained unchanged in simvastatin 80 mg/day (n=16), atorvastatin 40 mg/day (n=16) and placebo (n=16) groups over the study period. Our findings indicate that high serum levels of ADMA, a potential marker for endothelial dysfunction, may increase the risk of acute coronary syndromes. However, aggressive treatment with either simvastatin or atorvastatin did not reduce plasma ADMA levels.
The benefits of pharmaceutical innovations are widely diffused; they accrue to the healthcare providers, patients, employers, and manufacturers. We estimate the societal monetary benefits of simvastatin in Canada and its distribution among different beneficiaries overtime.
Monetary benefits to developing and generic manufacturers were estimated by calculating public and private revenues minus the development costs of simvastatin and the contribution toward further research and development. We used a dynamic Markov model to estimate monetary benefits to healthcare and employment sectors in terms of cost avoidance associated with prevented cardiovascular events, including stroke and myocardial infarction, and lost productivity due to disability and premature death in working population.
Cumulative monetary benefits of simvastatin from 1990 to 2009 were $4.8 billion (2010 CA$), of which developing and generic manufacturers, and healthcare and employment sectors accounted for 32 percent, 27 percent, 32 percent, and 9 percent, respectively. The yearly trend showed that after the patent expired in 2002 the generic manufacturers became dominant in the market. Benefits for the healthcare sector started to decrease from 2003 corresponding to the decreasing population taking simvastatin during the same time period. Sensitivity analysis showed the higher the compliance or the efficacy, the larger the benefits to healthcare and employment sectors, while monetary benefits for manufacturers were unchanged.
Societal monetary benefits of simvastatin are significant and the distributions of the benefits have changed overtime. Patent, compliance, and efficacy play a vital role in the estimation of the benefits. Analysis of all beneficiaries separately overtime is important when assessing the value of pharmaceutical innovation.
Patient compliance is crucial for the effectiveness of preventive medication. The aim of the study was to investigate changes in serum cholesterol levels and the use of cholesterol lowering drugs one year after the end of the Scandinavian Simvastatin Survival Study (4S), a randomized secondary prevention study of coronary heart disease with simvastatin and placebo.
A questionnaire asking the current use of cholesterol lowering drugs, most recent serum cholesterol value and attitudes towards cholesterol lowering was sent to 785 surviving 4S participants in four 4S centres in Finland. The response rate was 94%. The current use of cholesterol lowering drugs and the reported mean serum cholesterol values were similar to the original simvastatin and placebo groups. In all, 74% (n = 546) reported that they had used cholesterol lowering drugs after the study, and 63% (n = 467) were currently using them, mostly simvastatin (96%) with an average dose of 14 (SD 5) mg.day-1. Cholesterol lowering was considered to be 'very important' by 53% and 'important' by 37% of the respondents. The most frequent reasons for discontinuation were 'drug costs' (38%) and 'normal cholesterol values' (30%). The reported mean serum cholesterol levels were 5.1 (SD 1.0) and 5.7 (SD 1.1) mmol-1 in the current cholesterol lowering drug users and non-users, respectively (P
Comment In: Eur Heart J. 1997 Nov;18(11):1695-69402441
To describe the use and evaluate the effectiveness of different lipid lowering therapies in unselected patients with type 1 and type 2 diabetes in clinical practice.
Observational population-based study using the personal identification number to link information from the National Diabetes Register, the Prescribed Drug Register and the Patient register in Sweden. All patients in the NDR aged 18-75 years with diabetes more than one year were eligible, but only patients starting any lipid lowering treatment with at least three prescriptions 1 July 2006-30 June 2007 were included (n?=?37,182). The mean blood lipid levels in 2008 and reductions in LDL cholesterol were examined.
Blood lipid levels were similar in patients treated with simvastatin, atorvastatin and rosuvastatin, showing similar lipid lowering effect as currently used. Users of pravastatin, fluvastatin, ezetimib and fibrate more seldom reach treatment goals. Moderate daily doses of the statins were used, with 76% of simvastatin users taking 20 mg or less, 48% of atorvastatin users taking 10 mg, 55% of pravastatin users taking 20 mg, and 76% of rosuvastatin users taking 5 or 10 mg.
This observational study shows that the LDL-C levels in patients taking simvastatin, atorvastatin or rosuvastatin are very similar as currently used, as well as their LDL-C lowering abilities. There is potential to intensify lipid lowering treatment to reduce the remaining high residual risk and achieve better fulfilment of treatment goals, since the commonly used doses are only low to moderate.
Lysinuric protein intolerance (LPI) is an autosomal recessive disorder characterized by defective transport of cationic amino acids lysine, arginine, and ornithine. Low plasma concentrations of arginine and ornithine lead to impaired urea cycle function and, subsequently, decreased protein tolerance. Patients often develop natural aversion to protein-rich foods, which may predispose them to nutritional problems. The objective of this retrospective study was to investigate lipid values and efficacy of lipid-lowering therapy in patients with LPI.
Serum total and high-density-lipoprotein (HDL)-cholesterol and triglyceride concentrations were analyzed in 39 Finnish LPI patients (14 males) aged 3-64 years. Dietary intakes were analyzed from food records. Mean [standard deviation (SD)] serum and HDL-cholesterol and triglyceride concentrations were 7.16 (2.13) mmol/l, 1.21 (0.58) mmol/l, and 4.0 (2.4) mmol/l, respectively. Patients with renal dysfunction had marginally higher total cholesterol and significantly higher triglyceride concentration than patients without renal impairment. Twenty-two patients were started on 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (atorvastatin or simvastatin). After 6 months, serum cholesterol and triglyceride concentrations had decreased by 32% (p
We investigated whether intensive cholesterol lowering could more effectively prevent heart failure (HF) in secondary prevention. The IDEAL study was a 4.8-year prospective, randomized trial comparing "usual" simvastatin treatment (20 to 40 mg/day, n = 4,449) with high-dose atorvastatin (80 mg/day, n = 4,439) in patients with a history of myocardial infarction (MI). At baseline, 94% of patients (n = 8,351) had no history of HF. During the course of the trial, there were 222 new or recurrent hospitalizations for HF (57 and 165 in those with and without HF at baseline, respectively), 123 (2.8%) in the simvastatin group and 99 (2.2%) in the atorvastatin group (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.62 to 1.05, p = 0.11). After adjustments, atorvastatin 80 mg was associated with a 26% decrease of new HF events compared with simvastatin 20 to 40 mg (HR 0.74, 95% CI 0.57 to 0.97, p = 0.03). Atorvastatin tended to be associated with fewer HF events in those with HF at baseline (n = 537, HR 0.65, 95% CI 0.38 to 1.11, p = 0.11) and those without HF at baseline (n = 8,351, HR 0.80, 95% CI 0.59 to 1.09, p = 0.15). Also, HF without preceding MI (n = 187) was decreased (HR 0.73, 95% CI 0.54 to 0.97, p = 0.03). In conclusion, atorvastatin 80 mg was more efficient than simvastatin 20 to 40 mg in preventing development of HF in patients with previous MI.
AIM: To assess differences in treatment of ischaemic heart disease in the Scandinavian countries. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study (4S) lasted 5.4 years and showed that death rates in 4444 patients with coronary heart disease were 30% lower in those treated with simvastatin to lower serum cholesterol than in those given placebo. Apart from this main result, the 4S provided detailed information on rates of death and other manifestations of coronary heart disease, as well as on use of non-lipid forms of therapy. There were substantial differences in 4S placebo group rates of mortality, coronary deaths and major coronary events between countries. Surgical and medical therapy varied importantly between countries. CONCLUSIONS: Major inter-country differences in rates of death and myocardial infarction in patients with coronary heart disease were likely to be due to a composite of differences in baseline characteristics including smoking. They occurred in a setting of very uneven exploitation of the potential for improving survival of patients with ischaemic heart disease.
Comment In: Eur Heart J. 1998 Oct;19(10):14199820981