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PubMed2004

Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals.

Since Mg(2+)-ATP is the controlling factor for the rate-limiting enzyme in the cholesterol biosynthesis sequence that is targeted by the statin pharmaceutical drugs, comparison of the effects of Mg(2+) on lipoproteins with those of the statin drugs is warranted. Formation of cholesterol in blood, as well as of cholesterol required in hormone synthesis, and membrane maintenance, is achieved in a series of enzymatic reactions that convert HMG-CoA to cholesterol. The rate-limiting reaction of this pathway is the enzymatic conversion of HMG CoA to mevalonate via HMG CoA. The statins and Mg inhibit that enzyme. Large trials have consistently shown that statins, taken by subjects with high LDL-cholesterol (LDL-C) values, lower its blood levels 35 to 65%. They also reduce the incidence of heart attacks, angina and other nonfatal cardiac events, as well as cardiac, stroke, and total mortality. These effects of statins derive less from their lowering of LDL-C than from their reduction of mevalonate formation which improves endothelial function, inhibits proliferation and migration of vascular smooth muscle cells and macrophages, promotes plaque stabilization and regression, and reduces inflammation, Mg has effects that parallel those of statins. For example, the enzyme that deactivates HMG-CoA Reductase requires Mg, making Mg a Reductase controller rather than inhibitor. Mg is also necessary for the activity of lecithin cholesterol acyl transferase (LCAT), which lowers LDL-C and triglyceride levels and raises HDL-C levels. Desaturase is another Mg-dependent enzyme involved in lipid metabolism which statins do not directly affect. Desaturase catalyzes the first step in conversion of essential fatty acids (omega-3 linoleic acid and omega-6 linolenic acid) into prostaglandins, important in cardiovascular and overall health. Mg at optimal cellular concentration is well accepted as a natural calcium channel blocker. More recent work shows that Mg also acts as a statin.

Anticholesteremic Agents↗
PubMedDate not supplied

Statin use and cancer risk: an epidemiologic review.

While the beneficial effects of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on cardiovascular disease are well established, much uncertainty remains about their effects on cancer. The statins inhibit the rate-limiting step in the mevalonate pathway, leading to reduced levels of cholesterol and other molecules of importance for critical cellular processes. A growing body of preclinical data indicates that statins may have antineoplastic properties, but some studies raise the possibility that statins may possess a carcinogenic potential. Clinical and observational studies of the association between statin use and cancer have been inconclusive with regard to any chemopreventive or therapeutic effect, but they do provide reassuring evidence that statins do not appear to be carcinogenic. The reasons for the varying results are unclear but they may relate to methodological issues. Additional studies, including Phase II randomized trials and epidemiological studies with accurate measures of statin use and comprehensive control for confounding factors, are needed to determine the potentially beneficially effects of statins on cancer development and progression.

Adult↗
PubMed2003

Potential anticancer effects of statins: fact or fiction?

Deregulation of any of the steps in cell growth, proliferation and apoptosis may result in its malignant transformation. Statins, along with their lipid-lowering potential, modify several processes in the cell cycle. These agents inhibit cell proliferation and arrest cell cycle progression by interrupting growth-promoting signals. Statins selectively induce proapoptotic protential in tumor cells and synergistically enhance proapoptotic potential of several cytotoxic agents. Statins alter angiogenic potential of cells by modulating apoptosis inhibitory effects of VEGF and decrease secretion of metalloproteases. Statins also alter adhesion and migration of tumor cells, thereby inhibiting tumor invasion and metastasis. Statins suppress rate of activation of multiple coagulation factors and thus prevent coagulation-mediated angiogenesis. Statins have been shown to have anti-tumor activity in experimental models. Various anti-neoplastic properties of statins are probably a result of inhibition of posttranslational modifications of growth regulatory proteins. Molecular mechanisms of antiproliferative, proapoptotic and antiangiogenic effects of statins are reviewed in this chapter.

Animals↗
PubMed2005

Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants.

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE: The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN: Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS: LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS: Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.

Adult↗
PubMed2006

Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users: a report from the first Euro Heart Survey on acute coronary syndromes.

AIMS: Statins provide effective secondary prevention in cardiovascular disease. However, it remains uncertain how soon statins should be started after an acute coronary syndrome (ACS). Recently published trials suggest starting before discharge. We hypothesize that statins should be initiated without delay. METHODS AND RESULTS: Data from a large cohort of 10,484 consecutive patients with an ACS were analysed. Of this cohort, 1426 first-time statin receivers and survivors of the first 24 h were compared with 6771 first-day survivors not receiving statin therapy. A propensity score for the likelihood of receiving statin therapy within 24 h was developed and used with other established risk factors in a multivariable analysis. There was a significantly reduced all-cause 7-day mortality in patients receiving early statin therapy [0.4 vs. 2.6%, unadjusted hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.08-0.37, adjusted HR 0.34, 95% CI 0.15-0.79]. Statistical significance was observed in patients presenting with STE-ACS (adjusted HR 0.17, 95% CI 0.04-0.70) and not in NSTE-ACS patients. However, no statistical evidence of heterogeneity in treatment effect was observed between these groups. CONCLUSION: These data suggest that very early statin therapy is associated with reduced mortality in patients presenting with STE-ACS; however, these findings have to be confirmed by prospective, randomized controlled trials before firm treatment recommendations can be given.

Aged↗
PubMed2006

Statin drugs and risk of advanced prostate cancer.

BACKGROUND: Statins are commonly used cholesterol-lowering drugs that have proapoptotic and antimetastatic activities that could affect cancer risk or progression. Results from previous epidemiologic studies of the association between statin use and cancer have been inconsistent. We investigated the association of statin use with total and advanced prostate cancer, the latter being the most important endpoint to prevent. METHODS: We analyzed data from an ongoing prospective cohort study of 34,989 US male health professionals who were cancer free in 1990 and were followed to 2002. Participants reported their use of cholesterol-lowering drugs on biennial questionnaires. Prostate cancer diagnosis was confirmed by medical record review. Multivariable-adjusted relative risks (RRs) were estimated from Cox proportional hazards regression models. Statistical tests were two-sided. RESULTS: During 376,939 person-years of follow-up, we ascertained 2579 prostate cancer cases, 316 of which were advanced (regionally invasive, metastatic, or fatal). The age-standardized incidence rates of advanced prostate cancer were 38 and 89 per 100,000 person-years in current statin users and in past or never users, respectively. The multivariable-adjusted relative risk of advanced disease was 0.51 (95% confidence interval [CI] = 0.30 to 0.86) and of metastatic or fatal disease was 0.39 (95% CI = 0.19 to 0.77) for current statin use compared with no current use. The associations remained after adjusting for prostate-specific antigen screening history (advanced disease: RR = 0.57, 95% CI = 0.30 to 1.11; metastatic or fatal disease: RR = 0.35, 95% CI = 0.14 to 0.92). Risk of advanced disease was lower with longer statin use (P(trend) = .003); compared with never use, the relative risk for less than 5 years of use was 0.60 (95% CI = 0.35 to 1.03) and for 5 or more years of use was 0.26 (95% CI = 0.08 to 0.83). We found no association between statin use and risk of total prostate cancer (RR = 0.96, 95% CI = 0.85 to 1.09). CONCLUSIONS: In this cohort of male health professionals, use of statin drugs was not associated with risk of prostate cancer overall but was associated with a reduced risk of advanced (especially metastatic or fatal) prostate cancer.

Aged↗
PubMed2004

Statin use after renal transplantation: a systematic quality review of trial-based evidence.

BACKGROUND AND OBJECTIVES: HMG-CoA reductase inhibitor (statin) therapy reduces cardiovascular risk in the general population and may modulate rejection in solid organ transplant recipients. We assessed whether current clinical evidence supports the use of statins to improve cardiac and/or renal outcomes after kidney transplantation. METHODS: We performed a systematic review of randomized, controlled intervention trials of statins among renal allograft recipients. Clinical trials published between January 1, 1993 and January 1, 2004 were identified by systematic search of electronic databases. Eligible studies measured the impact of therapy on acute allograft rejection, surrogates of cardiovascular risk and/or cardiovascular morbidity and mortality. We abstracted descriptive summaries of trial design elements and primary effect estimates, and assessed trial quality with a standardized quality evaluation tool. RESULTS: Thirteen eligible trials were identified. Statin therapy was associated with less acute allograft rejection in two early studies but was ineffective in three subsequent, larger trials. Therapeutic benefit was also seen in six of seven small studies that evaluated cardiovascular risk surrogates. Statin use did not significantly alter the primary composite outcome in a single large cardiac events trial, but was associated with reductions in secondary end-points of cardiac death analysed alone or with myocardial infarction. Important design distinctions included statin preparation and dose, concomitant interventions, study power and randomization methods. Median total quality scores were 52 for the rejection trials, 41 for the studies of cardiovascular risk surrogates and 69 for the cardiac events trial, and showed a trend towards variation by outcome measure (P = 0.05). CONCLUSIONS: Heterogeneous study designs and methodological quality contribute to discrepant conclusions on the benefit of statin therapy to renal allograft recipients. Trial-based clinical evidence does not support the use of statins to lower acute rejection risk after kidney transplantation, but does indicate effectiveness for improvement in cardiovascular risk markers and possibly for reduction of clinical cardiac events.

Cardiovascular Diseases↗
PubMed2003

Cataract and the use of statins: a case-control study.

BACKGROUND: In animal studies, statins have induced cataract formation. Because incident cataract is relatively uncommon, studies in humans have been unable to exclude a clinically important effect. AIMS: To assess the risk of cataract associated with the use of statins, and whether it is increased by concurrent use of drugs that inhibit the cytochrome P450 system. DESIGN: Population-based case-control study. METHODS: Patients were randomly sampled from the UK General Practice Research Database. The study included 15,479 people with cataract and 15,479 controls matched for age, sex, practice and observation period. RESULTS: The crude odds ratio (OR) for the association between any recorded exposure to statins and cataract was 1.41 (95%CI 1.21-1.65), but this reduced to 1.04 (95%CI 0.89-1.23, p=0.6) after adjustment for consultation rate. There was no evidence that the risk increased with higher doses or longer duration of statin use, or that the risk varied by individual statin. There was no evidence that the risk of cataract was increased by concurrent use of statins and drugs that inhibit the cytochrome P450 system. DISCUSSION: In the short- and medium-term, statins do not seem to be associated with an increased risk of cataract. The need to assess the effects of long-term statin exposure on the eye remains.

Aged↗
PubMed2005

The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient.

The landmark HMG-CoA reductase inhibitor (statin) studies have practical lessons for clinicans. The 4S trial established the importance of treating the hypercholesterolaemic patient with cardiovascular heart disease. Next, WOSCOPS showed the benefit of treating healthy, high-risk hypercholesterolaemic men. CARE, a secondary prevention trial, showed the benefit of treating patients with cholesterol levels within normal limits. This was confirmed by the LIPID trial, another secondary prevention study, which enrolled patients with cholesterol levels 155-271 mg/dl (4-7 mmol/l). The importance of treating patients with established ischaemic heart disease, and those at high risk of developing heart disease, regardless of cholesterol level, was being realized. In the MIRACL trial, hypocholesterolaemic therapy was useful in the setting of an acute coronary syndrome, while the AVERT study showed that aggressive statin therapy is as good as angioplasty in reducing ischaemic events in patients with stable angina. By showing the value of fluvastatin after percutaneous intervention, LIPS confirmed that benefit is a class action of the statins. The HPS randomized over 20 000 patients, and showed beyond doubt the value of statins in reducing cardiovascular events in the high-risk patient. Although PROSPER showed benefit in treating the elderly patients above 70 years, statin therapy in this trial was associated with an increase in cancer incidence. The comparative statin trials, PROVE-IT, REVERSAL, Phase Z of the A to Z, ALLIANCE and TNT, all showed that high-dose statins will better reduce cardiovascular events in the high-risk patient, although the adverse effects of therapy will also be increased. ALLHAT-LLT, ASCOT-LLA and CARDS showed that for statin therapy to demonstrate a significant benefit, hypertensive or diabetic patients must be at sufficiently high risk of cardiovascular events. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not the lipid level of the patient. No therapy is free of adverse effect. Treatment of those most at risk will bring the most benefit; treatment of those not at high risk of cardiovascular disease may expose patients who would not benefit much from therapy to its adverse effects.

Adult↗
PubMed2006

Statins inhibit growth of human endometrial stromal cells independently of cholesterol availability.

Endometriosis is characterized by ectopic growth of endometrial tissues. Statins, inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), have been shown to decrease proliferation of several mesenchymal tissues. Actions of statins may be related to decreased availability of cholesterol as well as intermediate metabolites of the mevalonate pathway downstream of HMGCR. This study was designed to evaluate effects of statins on growth of endometrial stromal cells and to investigate mechanisms of these effects. Human endometrial stromal cells were cultured in the absence and in the presence of serum and with or without mevastatin and simvastatin. DNA synthesis and viable cell numbers were determined. Effects of statins were also evaluated in the presence of mevalonate and squalene. Furthermore, effects on phosphorylation of mitogen-activated protein kinase 3/1 (MAPK3/1) (also known as extracellular signal-regulated kinase [ERK1/2]) were determined. Mevastatin and simvastatin induced a concentration-dependent inhibition of DNA synthesis and viable cell count in chemically defined media and in the presence of serum. Mevalonate, but not squalene, abrogated inhibitory effects of statins on cell proliferation. Statins inhibited MAPK3/1 phosphorylation. This is the first study demonstrating that statins inhibit growth of endometrial stromal cells. This effect is also demonstrable in the presence of a supply of cholesterol and may be related to decreased activation of MAPK3/1. The present observations may be relevant to potential therapeutic use of statins in conditions such as endometriosis.

Cell Proliferation↗
PubMed2006

Potential benefit of statins for vascular disease in systemic sclerosis.

PURPOSE OF REVIEW: Microvascular abnormality is a dominant feature of systemic sclerosis. There is increasing evidence that statins, developed as lipid-lowering drugs, yield profound benefits beyond their lipid-lowering effects. These 'pleiotropic' effects suggest that statins may be beneficial for treating SSc vasculopathy. This review focuses on the action of statins on endothelial functions and their potential use in treating SSc. RECENT FINDINGS: The initial event in the pathogenesis of vascular involvement in SSc has been thought to be endothelial injury, but recent studies have led to another theory--that insufficient vascular repair due to defective vasculogenesis contributes to this process. Statins inhibit cholesterol synthesis, but they also suppress the synthesis of other lipid intermediates, resulting in protection of the endothelium through improvements in endothelial function, mobilization of endothelial precursors, suppression of the inflammatory response, and inhibition of fibrosis. Only a few studies evaluating the clinical benefits of statins have been conducted in SSc patients to date, but one open-label study showed that statins might be effective in improving vascular symptoms. SUMMARY: Statins display numerous effects that may be of potential benefit in preventing endothelial dysfunction in SSc patients. Further clinical trials of statins in SSc patients are warranted.

Blood Vessels↗
PubMed2006

Statin use and mortality within 180 days after bacteremia: a population-based cohort study.

OBJECTIVE: To examine the association between preadmission statin use and mortality among patients with bacteremia in a population-based setting. DESIGN: Observational study based on prospective registration of bacteremia episodes and mortality over a 6-yr period. SETTING: North Jutland County, Denmark (population, 500,000). PATIENTS: A total of 5,353 adult patients hospitalized with bacteremia from 1997 to 2002. Individuals treated with statins (n = 176) were identified by record-linkage with the County Prescription Database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared mortality rates 0-30 and 31-180 days after bacteremia in patients with and without preadmission statin use, adjusted for gender, age group, level of comorbidity, alcohol-related conditions, use of immunosuppressive drugs and systemic antibiotics, and focus on infection. The 30-day mortality in statin users vs. nonusers was similar (20.0% vs. 21.6%, adjusted mortality rate ratio 0.93, 95% confidence interval 0.66-1.30). Among survivors after 30 days, however, statin therapy was associated with a substantially decreased mortality up until 180 days after the bacteremia (8.4% vs. 17.5%, adjusted mortality rate ratio 0.44, 95% confidence interval 0.24-0.80). This tendency toward similar short-term and decreased longer term mortality associated with statin use was observed consistently in both community-acquired and nosocomial bacteremia episodes and when analyses were restricted to patients with previous cardiovascular discharge diagnoses or diabetes. CONCLUSIONS: This study provides evidence against the hypothesis that statin use has an effect on short-term mortality after bacteremia. Statin use was, however, associated with a substantially decreased mortality between 31 and 180 days after bacteremia.

Adolescent↗
PubMed2004

Phenotypes, genotypes and response to statin therapy.

PURPOSE OF REVIEW: Response to statin treatment can vary widely from person to person as a result of inherited traits (genotype) and acquired characteristics such as obesity (phenotype). The aim of this review is to describe what is known about factors that determine a patient's response, and to offer a mechanism to explain how plasma triglyceride influences the nature and magnitude of lipid lowering on statin therapy. RECENT FINDINGS: In normotriglyceridemic individuals statins have little impact on the concentration of large VLDL, but as basal plasma triglyceride rises there is an increasing tendency for large VLDL, chylomicrons, chylomicron remnants and small, dense LDL to fall on treatment. These phenotype-dependent effects are in contrast to the phenotype-independent actions on IDL and LDL. Recent studies have also revealed that the principal mechanism by which statins lower VLDL (and LDL) in hypertriglyceridemic individuals is by stimulation of lipoprotein clearance. Individuals with low HDL-cholesterol are increasingly treated with statins. The increase in this lipoprotein affects the subfraction distribution, with a specific increase in alpha1 HDL components. Polymorphism in the promoter for the ABCG8 gene has been linked to variations in response to statins; individuals with the rarer D19H genotype exhibit a greater reduction in LDL-cholesterol. Similarly, the magnitude of the statin-induced increase in HDL-cholesterol has been linked to a polymorphism in the promoter for apolipoprotein A1. SUMMARY: Statins are administered to a wide range of individuals on an empirical basis. Investigation of the phenotype and genotype influences on treatment response will allow a more tailored use of these drugs.

Apolipoprotein A-I↗
PubMed2005

Statin-induced myositis: a commonly encountered or rare side effect?

PURPOSE OF REVIEW: Statins are well established as first-line agents for cholesterol lowering in cardiovascular disease, with accumulating evidence supporting their initiation and guidelines recommending treatment to lower LDL levels. Although generally well tolerated with few side effects, including headaches and gastrointestinal symptoms, concerns are raised regarding myopathy, which may lead to fatal rhabdomyolysis. This review examines current evidence on statin interactions, mechanism of injury and toxicity. RECENT FINDINGS: Significant myopathy is rare with an incidence of less than 0.5% of patients. Statin side effects may be dose-related, associated with other drug interactions that interfere with statin metabolic pathways through cytochrome p450 pathways or glucuronidation, or related to co-morbidities. Several theories have suggested that statin myotoxicity may be due to intracellular cholesterol depletion, or interference with oxidative phosphorylation pathways. Exact mechanisms are yet to be fully defined. Individuals with mixed dyslipidaemia may require combination therapy to achieve target lipid levels. No large-scale randomized trials have yet reported on the safety of combination therapy, although more recent studies may shed some light when they report. CONCLUSION: As most individuals on statins are 'high-risk' patients, they tend to be on multiple agents for cardiovascular disease which may interact with their statin. Progression of myalgia or myositis to rhabdomyolysis is rare (one in 30-100,000 patient-years of exposure), but if progressive muscle symptoms are ignored then fatalities can occur. When prescribing statins, physicians should be alert to potential risks and educate patients to report any potentially significant symptoms.

Humans↗
PubMed2005

Clinical implications for statin pleiotropy.

PURPOSE OF REVIEW: Atherosclerosis is a multi-factorial condition involving dyslipidemia that can result in cardiovascular disease. Statins are potent inhibitors of cholesterol biosynthesis, and in clinical trials, statins have been shown to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to occur much earlier and to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. SUMMARY OF FINDINGS: Recent studies indicate that some of the cholesterol-independent or 'pleiotropic' effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent upon isoprenylation, may play an important role in mediating the pleiotropic effects of statins. SUMMARY: The potential clinical implications of statin pleiotropy suggests that perhaps other biomarkers, in addition to lipid levels, should be used to gauge the full efficacy of statin therapy in patients with cardiovascular risks or that statin therapy may be effective in disease states, such as inflammatory conditions, ischemic stroke or cancer, where elevated cholesterol levels have not been shown to be a strong epidemiological risk for these diseases.

Atherosclerosis↗
PubMed2005

Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997-2003.

AIMS: To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. METHODS: Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997-2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of "patient treatment days" (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. RESULTS: Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274% in Ireland and by 56% in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). CONCLUSIONS: Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance.

Drug Prescriptions↗
PubMed2004

The use of statins in optimising reduction of cardiovascular risk: focus on fluvastatin.

Patients with widely differing degrees of cardiovascular risk can derive benefit from effective lipid-lowering therapy with statins, including patients with normal or low cholesterol levels. Clinical trials with fluvastatin have shown that it is effective in patients across a broad spectrum of cardiovascular risk. The lipid-lowering effects of fluvastatin are smaller than some statins, but major clinical outcome studies have consistently demonstrated morbidity and mortality benefits with reductions of low-density lipoprotein cholesterol of <30%. As treatment with statins is generally life-long and patients often receive multiple concomitant medications, optimal statin therapy should be well tolerated and serious consideration should be given to the avoidance of drug interactions. Although serious side-effects of statins are very rare, it is important that fluvastatin is less susceptible to drug interactions than other statins, because serious side-effects of statin therapy are generally associated with concomitant medications affecting statin metabolism. In addition, an extended-release formulation of fluvastatin has been developed to provide liver selectivity with a sustained exposure to the drug, thus improving its efficacy, and safety and tolerability profiles.

Anticholesteremic Agents↗
PubMed2004

Statin use in Type 2 diabetes mellitus is associated with a delay in starting insulin.

AIMS: It has been suggested that HMG Co-A reductase inhibitors ('statins') may reduce the risk of developing Type 2 diabetes mellitus. This study was designed to evaluate whether use of statins would also delay progression to insulin therapy. METHODS: This was a retrospective cohort study using Saskatchewan Health databases to identify subjects newly started on oral antidiabetic agents from 1991 to 1996. SUBJECTS: < 30 years of age or with previous lipid-lowering drug use were excluded. Medications known to influence glycaemic control, co-morbidity, and demographic data were collected. Statin exposure was defined as at least 1 year of use. Primary outcome was starting insulin treatment. Multivariate Cox proportional hazards models were used to examine the association between statin use and starting insulin. RESULTS: The final cohort included 10,996 new users of oral antidiabetic agents, of which 484 (4.4%) used statins. Mean age was 64 years and 55% were male. Mean duration of follow-up was 5.1 years; 11.1% (n = 1221) eventually started insulin treatment. Statin users were no less likely than non-users to start insulin treatment eventually (11.6% vs. 11.1%, P = 0.74). After multivariate adjustment, however, statin use was associated with a 10-month delay before newly treated diabetic subjects needed to start insulin treatment (adjusted hazard ratio 0.74; 95% confidence interval 0.56, 0.97, P = 0.028). CONCLUSION: The use of statins is associated with a delay in starting insulin treatment in patients with Type 2 diabetes initially treated with oral antidiabetic agents. Whether this relationship exists for patients at high risk of developing diabetes should be examined in a randomized trial.

Administration, Oral↗