(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Cardiovascular-Diseases

A detailed summary and meta-analysis of the dose-related effect of pravastatin on lipids is not available.. Primary objective To assess the pharmacology of pravastatin by characterizing the dose-related effect and variability of the effect of pravastatin on the surrogate marker: low-density lipoprotein (LDL cholesterol). The effect of pravastatin on morbidity and mortality is not the objective of this systematic review. Secondary objectives • To assess the dose-related effect and variability of effect of pravastatin on the following surrogate markers: total cholesterol; high-density lipoprotein (HDL cholesterol); and triglycerides. • To assess the effect of pravastatin on withdrawals due to adverse effects.. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to September 2021: CENTRAL (2021, Issue 8), Ovid MEDLINE, Ovid Embase, Bireme LILACS, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.. Randomized placebo-controlled trials evaluating the dose response of different fixed doses of pravastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without evidence of cardiovascular disease.. Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered lipid data from placebo-controlled trials into Review Manager 5 as continuous data and withdrawal due to adverse effects (WDAEs) data as dichotomous data. We searched for WDAEs information from all trials. We assessed all trials using Cochrane's risk of bias tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases.. Sixty-four RCTs evaluated the dose-related efficacy of pravastatin in 9771 participants. The participants were of any age, with and without evidence of cardiovascular disease, and pravastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over the doses of 5 mg to 160 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol, and a weak linear dose-related effect on blood triglycerides. There was no dose-related effect of pravastatin on blood HDL cholesterol. Pravastatin 10 mg/day to 80 mg/day reduced LDL cholesterol by 21.7% to 31.9%, total cholesterol by 16.1% to 23.3%,and triglycerides by 5.8% to 20.0%. The certainty of evidence for these effects was judged to be moderate to high. For every two-fold dose increase there was a 3.4% (95% confidence interval (CI) 2.2 to 4.6) decrease in blood LDL cholesterol. This represented a dose-response slope that was less than the other studied statins: atorvastatin, rosuvastatin, fluvastatin, pitavastatin and cerivastatin. From other systematic reviews we conducted on statins for its effect to reduce LDL cholesterol, pravastatin is similar to fluvastatin, but has a decreased effect compared to atorvastatin, rosuvastatin, pitavastatin and cerivastatin. The effect of pravastatin compared to placebo on WADES has a risk ratio (RR) of 0.81 (95% CI 0.63 to 1.03). The certainty of evidence was judged to be very low.. Pravastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. This review did not provide a good estimate of the incidence of harms associated with pravastatin because of the lack of reporting of adverse effects in 48.4% of the randomized placebo-controlled trials.

Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Drug-Related Side Effects and Adverse Reactions; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Infant; Infant, Newborn; Pravastatin; Rosuvastatin Calcium

Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known.. Primary objective To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease. To compare the effect of pitavastatin on surrogate markers with other statins.  Secondary objectives To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects.  SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.. RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.. Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.. Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects.. Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.

Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Controlled Before-After Studies; Drug Administration Schedule; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pyridines; Quinolines; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Sex Factors; Triglycerides

Hyperlipidemia and cardiovascular disease are risk factors for long-term renal transplant dysfunction. However, no meta-analyses of randomized controlled trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effects of statin use on renal transplant patients using a meta-analysis approach.. We conducted a systematic review and meta-analysis using random effects modeling. We searched the following databases for all studies published through to June 15, 2018: Cochrane Central Register, OVID MEDLINE, Embase, and PubMed. We reviewed all relevant reviews, registered trials, and relevant conference proceedings to compare clinical outcomes and survival between fluvastatin recipients and controls.. Five trials with a total of 3725 patients were included. Glomerular filtration rates, graft loss, tacrolimus level, antibody-mediated rejection, T cell-mediated rejection, proteinuria, fungal infection (candida), and patient survival rates did not differ between the fluvastatin and control groups. However, major adverse cardiovascular events were 1.547 times more common in the control group than in the fluvastatin group (P = .001).. Fluvastatin use was associated with a reduction in major adverse cardiac events among kidney transplant patients.

Topics: Cardiovascular Diseases; Fluvastatin; Graft Rejection; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Transplantation

The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations.. We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes.. In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile.. All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.

Topics: Atorvastatin; Cardiovascular Diseases; Cause of Death; Chemical and Drug Induced Liver Injury; Double-Blind Method; Fluvastatin; Headache; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Lovastatin; Middle Aged; Muscular Diseases; Nausea; Neoplasms; Network Meta-Analysis; Placebos; Pravastatin; Randomized Controlled Trials as Topic; Risk Assessment; Rosuvastatin Calcium; Simvastatin; Withholding Treatment

Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A systematic multiple-database search was carried out to identify randomized controlled trials (RCTs) that investigated the effect of statins on plasma vWF:Ag levels. Random-effect meta-analysis of 21 treatment arms revealed a significant decrease in plasma vWF:Ag levels following statin therapy (SMD: -0.54, 95 %CI: -0.87, -0.21, p=0.001). In subgroup analyses, the greatest effect was observed with simvastatin (SMD: -1.54, 95 %CI: -2.92, -0.17, p=0.028) and pravastatin (SMD: -0.61, 95 %CI: -1.18, -0.04, p=0.035), but not with fluvastatin (SMD: -0.34, 95 %CI: -0.69, 0.02, p=0.065), atorvastatin (SMD: -0.23, 95 %CI: -0.57, 0.11, p=0.179) and rosuvastatin (SMD: -0.20, 95 % CI: -0.71, 0.30, p=0.431). The lowering effect of statins on plasma vWF:Ag levels was greater in the subset of studies lasting ≥ 12 weeks (SMD: -0.70, 95 %CI: -1.19, -0.22, p=0.005) compared with that of studies lasting < 12 weeks (SMD: -0.34, 95 %CI: -0.67, 0.003, p=0.052). Finally, low-intensity statin therapy was not associated with a significant reduction in vWF:Ag levels (SMD: -0.28, 95 %CI: -0.82, 0.27, p=0.320), but a significant effect was observed in high-intensity statin trials (SMD: -0.66, 95 %CI: -1.07, -0.24, p=0.002). This meta-analysis of available RCTs demonstrates a significant reduction in plasma vWF:Ag levels following statin therapy.

Topics: Adult; Aged; Antigens; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Pravastatin; Randomized Controlled Trials as Topic; Regression Analysis; Risk Assessment; Rosuvastatin Calcium; Simvastatin; Thrombosis; von Willebrand Factor; Young Adult

Pulse wave velocity (PWV) is a method to estimate arterial stiffness. Statins have been shown to improve the compliance of the vasculature. We present the available data from randomized controlled trials (RCTs) on the effect of statin administration on arterial stiffness by measuring PWV.. We considered all RCTs evaluating PWV following the administration of statins. We searched PubMed up to July 2009. Information regarding the author, journal, year of publication, randomization method, participant characteristics, treatment intervention, PWV assessment, and outcome were recorded independently by two investigators.. We found 9 eligible studies with 471 participants. The most frequent comparison was between fluvastatin against placebo, and the most extensively studied agent was also fluvastatin (n = 4 trials, total population = 240). The most frequent indication for statin therapy was hyperlipidaemia (n = 6), with or without other cardiovascular risk factors. Aortic PWV, which is considered to be the most appropriate method for PWV evaluation, was assessed in 4 studies, with significant reduction (improvement of arterial stiffness) in 2 studies, a non-significant change in one study and a significant increase in the other. Peripheral (mainly brachial-ankle) PWV was assessed in the other 5 studies with significant reduction in all except the one multi-arm study where only fluvastatin improved PWV.. We cannot safely conclude for the effect of statins on arterial stiffness, as estimated by PWV measurements. This is a poorly investigated field with few RCTs and a limited number of participants. More trials should be carried out to reach more robust conclusions.

Topics: Arteries; Blood Flow Velocity; Cardiovascular Diseases; Early Diagnosis; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Randomized Controlled Trials as Topic; Vascular Resistance

This study aimed to evaluate the effectiveness of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) in primary prevention of cardiovascular events.. The role of statins is well established for secondary prevention of cardiovascular disease (CVD) clinical events and mortality. Little is known of their role in primary cardiovascular event prevention.. We conducted comprehensive searches of 10 electronic databases from inception to May 2008. We contacted study investigators and maintained a comprehensive bibliography of statin studies. We included randomized trials of at least 12-month duration in predominantly primary prevention populations. Two reviewers independently extracted data in duplicate. We performed random-effects meta-analysis and meta-regression, calculated optimal information size, and conducted a mixed-treatment comparison analysis.. We included 20 randomized clinical trials. We pooled 19 trials (n = 63,899) for all-cause mortality and found a relative risk (RR) of 0.93 (95% confidence interval [CI]: 0.87 to 0.99, p = 0.03 [I(2) = 5%, 95% CI: 0% to 51%]). Eighteen trials (n = 59,469) assessed cardiovascular deaths (RR: 0.89, 95% CI: 0.81 to 0.98, p = 0.01 [I(2) = 0%, 95% CI: 0% to 41%]). Seventeen trials (n = 53,371) found an RR of 0.85 (95% CI: 0.77 to 0.95, p = 0.004 [I(2) = 61%, 95% CI: 38% to 77%]) for major cardiovascular events, and 17 trials (n = 52,976) assessed myocardial infarctions (RR: 0.77, 95% CI: 0.63 to 0.95, p = 0.01 [I(2) = 59%, 95% CI: 24% to 74%]). Incidence of cancer was not elevated in 10 trials (n = 45,469) (RR: 1.02, 95% CI: 0.94 to 1.11, p = 0.59 [I(2) = 0%, 95% CI: 0% to 46%]), nor was rhabdomyolysis (RR: 0.97, 95% CI: 0.25 to 3.83, p = 0.96 [I(2) = 0%, 95% CI: 0% to 40%]). Our analysis included a sufficient sample to reliably answer our primary outcome of CVD mortality.. Statins have a clear role in primary prevention of CVD mortality and major events.

Topics: Anticholesteremic Agents; Atorvastatin; Cardiovascular Diseases; Confidence Intervals; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lovastatin; Pravastatin; Pyrroles; Randomized Controlled Trials as Topic; Risk

The ASCOT-LLA and ALLHAT-LLT trials provide conflicting evidence of the efficacy of statins in decreasing cardiovascular (CV) morbidity and mortality in hypertensive patients. We performed a meta-analysis to compare the overall efficacy of statins in hypertensive and nonhypertensive patients enrolled in major randomized clinical trials. We systematically reviewed PubMed publications from 1985 onward for placebo-controlled randomized trials that examined the effect of statins on cardiac morbidity and mortality. Only trials that followed >or=1,000 patients for >or=2 years were included in the meta-analysis. Outcomes included cardiac or CV death, major coronary events, or major CV events. Pooled estimates of relative risk (RR) were calculated separately for hypertensive and nonhypertensive patients. The moderating effect of the percentage of hypertensive patients at baseline was tested using meta-regression. Besides the ASCOT-LLA and ALLHAT-LLT, 12 trials enrolling 69,984 patients met inclusion criteria. Overall, in these 12 trials, statin therapy decreased cardiac death by 24% (RR 0.76, 95% confidence interval [CI] 0.71 to 0.82). There was no evidence of difference in RR estimates for hypertensive (RR 0.78, 95% CI 0.72 to 0.84) and nonhypertensive (RR 0.76, 95% CI 0.72 to 0.80) patients. Similarly, meta-regression showed that the efficacy of statins was not moderated by the percentage of hypertensive patients at baseline (Q estimate 1.51, p=0.22). In conclusion, statin therapy effectively decreases CV morbidity and mortality to the same extent in hypertensive and nonhypertensive patients.

Topics: Aged; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Male; Middle Aged; Pravastatin; Prognosis; Pyrroles; Randomized Controlled Trials as Topic; Simvastatin; Therapeutics

Fluvastatin was the first synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) to be developed and is used in the management of dyslipidaemia in primary and secondary prevention of cardiovascular disease.. This article reviews the properties of fluvastatin and experience accrued through its use in clinical practice and clinical trials.. Relevant publications were identified through the PubMed database and product information held by the US Federal Drug Administration was also reviewed.. In the authors' opinion, fluvastatin exhibits a favourable safety profile in comparison to other statins, with a low incidence of adverse effects and a reduced propensity for interactions with other drugs. However, fluvastatin is a less potent cholesterol-lowering agent than newer statins on the market and its future predominant use is likely to be in niche patient groups at risk of side effects or drug interactions with other agents.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Clinical Trials as Topic; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Practice Guidelines as Topic; Risk Factors

This pooled analysis of 30 completed clinical trials assessed the efficacy and safety profile in reducing cardiovascular disease (CVD) risk of fluvastatin in the treatment of dyslipidemia in patients with and without the metabolic syndrome (metS).. Data from 30 double-blind, randomized, placebo-controlled or fluvastatin-controlled trials with > or =6 weeks of active treatment and daily fluvastatin doses of 20, 40, and 80 mg were pooled. Patients received fluvastatin or placebo. Linear contrasts from an analysis of covariance model containing factors for trial and treatment group (immediate-release fluvastatin 20, 40, 80 mg; extended-release fluvastatin 80 rag; or placebo), and using the baseline value as covariate, were used to compare the percentage changes from baseline to the first postbaseline assessment of all lipid parameters. A Cox regression analysis compared the all-fluvastatin group to the placebo group with regard to the time to occurrence of clinical end points from 5 pooled studies, each with a mean treatment duration >1 year wherein clinical end points were reviewed by an adjudication committee. These analyses were performed separately for patients with and without metS.. This pooled analysis included data from 7043 patients (4095 men, 2948 women; all-fluvastatin group with and without metS, 2529 and 2052 patients, respectively; placebo group with and without metS, 1514 and 948 patients, respectively). Patients with metS in the pooled fluvastatin group had a greater mean reduction in triglyceride levels (24.1% vs 6.7%), a greater mean increase in high-density lipoprotein cholesterol levels (10.3% vs -0.6%), and a similar mean reduction in low-density lipoprotein cholesterol levels (26.8% vs 26.7%) compared with the subgroup of patients without metS. Treatment with fluvastatin was associated with a significantly lower incidence of major adverse cardiovascular events (MACEs) (16.4% vs 22.0%) and an increase in the time to first MACE in patients with metS compared with placebo (hazard ratio = 0.728; P = 0.001). The incidences of adverse events, particularly those of concern (ie, myalgia and/ or increased blood creatine phosphokinase, alanine aminotransferase, and/or aspartate aminotransferase) with lipid-lowering therapy, were statistically similar between the patients who received fluvastatin and those who received placebo in the 2 subgroups.. The results from this pooled analysis found that fluvastatin was effective in reducing CVD risk in the treatment of dyslipidemia in these patients with metS.

Topics: Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Indoles; Male; Metabolic Syndrome; Middle Aged; Triglycerides

Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipid-lowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) guidelines. We reviewed recent studies on efficacy, tolerability and prescription recommendations of statins in CKD and renal transplant patients.. We searched Medline, the international medical database, to conduct a systematic review of the literature on the efficacy and tolerability of statins in CKD and renal transplant patients and on specific recommendations for dosage adjustments in this population.. The efficacy of statins in decreasing total cholesterol and LDL-cholesterol levels in dialysis and renal transplant patients is similar to that in the general population. On the other hand, large-scale randomized clinical trials among CKD (4D) and renal transplant (ALERT) patients do not demonstrate that statins significantly decrease rates of cardiovascular disease. They have a beneficial effect on proteinuria and lower the rate of kidney function deterioration in patients with dyslipidemia. Early introduction of a statin in transplant patients did not lead to improved kidney function or prevent loss of the graft. Although most statins are not excreted by the kidneys, the dosage of some must be adapted in CKD patients because of pharmacokinetic modifications induced by renal impairment.. Statins at appropriately adapted doses have the same efficacy in CKD patients as in subjects with normal kidney function, and tolerance is not a problem. Their effectiveness in cardiovascular prevention in this population has not been demonstrated to date. Results about statin-induced kidney protection are encouraging but further and more specific studies are needed.

Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Dyslipidemias; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Graft Rejection; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Indoles; Kidney Failure, Chronic; Liver Transplantation; Middle Aged; Pravastatin; Primary Prevention; Prospective Studies; Proteinuria; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Factors; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Time Factors

The predominance of small, dense low density lipoproteins (LDL) has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III; in fact, LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease. Several studies have also shown that the therapeutical modulation of LDL size is of great benefit in reducing the risk of cardiovascular events. Hypolipidemic treatment is able to alter LDL subclass distribution and statins are currently the most widely used lipid-lowering agents. Statins are potent inhibitors of hydroxy-methyl-glutaryl-coenzyme A reductase, the rate-limiting enzyme in hepatic cholesterol synthesis and are the main drugs of choice for the treatment of elevated plasma LDL cholesterol concentrations. Statins potentially lower all LDL subclasses (e.g., large, medium and small particles); thus, their net effect on LDL subclasses or size is often only moderate. However, a strong variation has been noticed among the different agents: analyses of all published studies suggest a very limited role of pravastatin and simvastatin in modifying LDL size and their subclasses, while fluvastatin and atorvastatin seem to be much more effective agents. Finally, rosuvastatin, the latest statin molecule introduced in the market, seems to be promising in altering LDL subclasses towards less atherogenic particles.

Topics: Anticholesteremic Agents; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lipoproteins, LDL; Particle Size; Pyrimidines; Pyrroles; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Topics: Cardiovascular Diseases; Cholesterol; Dyslipidemias; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Indoles; Kidney Diseases; Kidney Transplantation; Lipid Metabolism; Practice Guidelines as Topic; Renal Dialysis; Risk Factors; Triglycerides

Placebo-controlled clinical trials have shown that atorvastatin is beneficial in patients with myocardial ischemia, established coronary artery disease, hypertension and 3 other cardiovascular risk factors (e.g. left-ventricular hypertrophy, type 2 diabetes, smoking), and in diabetes, but not in patients with calcific aortic stenosis. Recently, intensive low density lipoprotein (LDL)-cholesterol lowering with atorvastatin 80 mg/day has been shown to have a greater clinical benefit than atorvastatin 10 mg/day in patients with coronary heart disease and one other high-risk factor (previous myocardial infarction, coronary revascularization or angina), and to be superior to moderate lipid lowering with pravastatin (40 mg/day) in patients with an acute coronary syndrome. However, a smaller study comparing lovastatin 5 mg/day with atorvastatin 80 mg/day was unable to detect any difference in outcomes in patients with stable coronary disease, despite the greater LDL-cholesterol lowering with the atorvastatin, possibly because it was not powered to do so. In a retrospective cohort study, atorvastatin 10 mg/day, pravastatin 20 mg/day, simvastatin 20 mg/day, lovastatin 20 mg/day and fluvastatin 20 mg/day had similar efficacy as secondary prevention after acute myocardial infarction. At present, the evidence from clinical trials is favouring the intensity of the effect on LDL-cholesterol and/or C-reactive protein (CRP) with atorvastatin 80 mg, rather than the use of atorvastatin per se, when greater benefits are observed with the 80 mg dose of atorvastatin compared to other statins. Thus, at present, it is not clear whether atorvastatin is superior to other statins in some indications (coronary heart disease, acute coronary syndromes) or whether it is the intensive lipid lowering that is responsible for the superiority. Atorvastatin has little or no ability to increase high density lipoprotein (HDL)-cholesterol, and this may be a disadvantage in patients with metabolic syndrome or diabetes, where low HDL-cholesterol is a key feature. Thus, other statins should probably be preferred to atorvastatin in patients with diabetes/metabolic syndrome. Alternatively, atorvastatin can be used in combination with a fibrate to increase HDL-cholesterol in patients with diabetes/metabolic syndrome.

Topics: Amlodipine; Anticholesteremic Agents; Atorvastatin; Azetidines; Cardiovascular Diseases; Clinical Trials as Topic; Clofibric Acid; Ezetimibe; Fatty Acids, Monounsaturated; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Indoles; Pravastatin; Pyrimidines; Pyrroles; Rosuvastatin Calcium; Simvastatin; Sulfonamides

The importance of statin therapy in lipid-lowering and its role in primary and secondary prevention has been borne out of numerous clinical trials conducted over the last two decades. Concurrently, much concern has been expressed over the safety and tolerability of these drugs. Fluvastatin has demonstrated good clinical efficacy and safety. This paper reviews the various pharmacological properties and evidence supporting its use in the prevention of cardiac events.

Topics: Age Factors; Animals; Cardiovascular Diseases; Cholesterol, LDL; Cholinergic Antagonists; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Randomized Controlled Trials as Topic; Rhabdomyolysis

Therapy with HMG-CoA reductase inhibitors (statins) has been shown to significantly reduce major coronary events and death in a wide range of individuals at risk for these events. In addition, recent observations suggest that some of the clinical benefits associated with statin therapy may be pleiotropic; that is, independent of their cholesterol-inhibiting action. It is clear that the clinical benefits associated with statin therapy far outweigh the risks; however, there may be important clinical differences among agents within the class, related to both benefits and drug safety. Evaluation of the benefit-to-risk profile for each available statin should include considering the results of randomised clinical outcome trials, the safety record of each agent, effect on lipoproteins and evidence of beneficial pleiotropic properties.Recently, data from several clinical outcome trials have shown that substantial benefits are associated with treatment with fluvastatin in diverse populations. In particular, data from two large, randomised clinical trials have demonstrated that fluvastatin is effective for secondary prevention of cardiac events in patients following coronary intervention procedures, and for primary prevention of cardiac events in renal transplant recipients. Pleiotropic benefits for fluvastatin have been shown in experimental and clinical studies as well. Fluvastatin was the first statin available as an extended-release product (fluvastatin XL 80mg); both formulations have demonstrated efficacy and safety in a wide range of patients. Taken together, these clinical outcomes and safety data suggest a strong benefit-to-risk profile for fluvastatin.

Topics: Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hypolipidemic Agents; Indoles; Randomized Controlled Trials as Topic; Risk Assessment

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.

Topics: Anticholesteremic Agents; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Indoles; Randomized Controlled Trials as Topic; Risk Factors

Topics: Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Cyclosporine; Cytochrome P-450 CYP3A; Drug Interactions; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immunosuppressive Agents; Indoles; Kidney Transplantation; Oxidoreductases, N-Demethylating; Primary Prevention; Risk Factors

Statins act by competitive inhibition of HMG-CoA reductase, a key enzyme regulating cholesterol synthesis. Reduction in serum LDL, the crucial biological expression dependent on this mechanism, varies in intensity as a function of the type and of the dose of statin.. Besides their lipid lowering effect, statins have also been demonstrated to have pleiotropic effects mostly directly related to HMG-CoA reductase inhibition.. Several clinical studies investigating prevention of cardiovascular disease have established that statins decrease cardiovascular morbidity and mortality. Results have been very coherent for both primary and secondary prevention with statins. The cardiovascular benefit is most likely partly related to its pleiotropic effects, particularly those inducing a stabilization of the atheromatous plaques.. Interventional studies have clearly established the role of statins in comparison with other lipid lowering agents for the prevention of cardiovascular events in most situations although a few therapeutic choices remain a subject of debate. Globally, the primary indications of statins are hypercholesterolemia and mixed hyperlipidemia with moderately elevated triglycerides. There are still some questions concerning the therapeutic goals of statin therapy.

Topics: Anticholesteremic Agents; Atorvastatin; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Lovastatin; Pravastatin; Pyridines; Pyrroles; Simvastatin

The largest population that suffers from cardiovascular events are subjects at moderate cardiovascular risk. However, no effective and safe preventive treatment is available for this population. We investigated whether their arterial wall phenotype could be turned to a lower risk direction by low-dose fluvastatin/valsartan combination (low-flu/val).. Twenty males at moderate cardiovascular risk (as classified by SCORE) were blindly randomized into the intervention group (N.=10, low-flu/val: 10 mg/20 mg) or control group (N.=10, placebo). At inclusion and after 30 days of treatment, brachial flow-mediated dilatation (FMD), β-stiffness coefficient, carotid pulse wave velocity (c-PWV), carotid-femoral PWV, Reactive Hyperemia Index, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1, total antioxidant status and expression of several protective genes (SIRT1, mTOR, NF-κB1, NFE2L2, PRKAA1) were followed.. Treatment resulted in improved FMD (from 3% to 4.2%, P=0.008), c-PWV (from 6.7 to 6.2 m/s, P=0.006), hs-CRP (from 5.39 to 3.35 mg/L, P=0.041) and SIRT1 expression (3.34-fold difference, P=0.047). No other vascular, inflammation and genetic parameters changed. The hs-CRP values after intervention correlated significantly with SIRT1 expression. The improved FMD persisted even 10 weeks after treatment discontinuation. The obtained changes were not followed by changes of lipids or blood pressure. Overall, the results revealed improvement in three different, although interrelated preventive arterial wall characteristics.. This pilot study revealed that intervention with low-flu/val importantly shifts the arterial wall phenotype in a lower risk direction. This improvement could be interpolated into clinical benefits that remain to be further studied.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Arteries; Biomarkers; Cardiovascular Diseases; Double-Blind Method; Drug Combinations; Fluvastatin; Gene Expression Regulation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Phenotype; Pilot Projects; Risk Factors; Slovenia; Time Factors; Treatment Outcome; Valsartan; Vascular Stiffness; Vasodilation

Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study.. Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107).. Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 μmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 μmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 μmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13-5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36-4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63-10.69) and 2.50 (95% CI, 1.38-4.55), respectively.. Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Creatinine; Disease Progression; Europe; Fatty Acids, Monounsaturated; Female; Fluvastatin; Graft Rejection; Graft Survival; Homoarginine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; North America; Proportional Hazards Models; Prospective Studies; Renal Insufficiency; Risk Factors; Time Factors; Treatment Outcome

To assess the efficacy and safety of fluvastatin sodium extended-release tablets (fluvastatin XL) 80 mg once daily compared to fluvastatin sodium immediate-release capsules (fluvastatin IR) 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk.. In this multi-center, randomized, double-blind, double-dummy, active-controlled, parallel-group study, after 6-week open-label treatment with fluvastatin IR 40 mg once daily, patients who did not reach their lipid goals were randomized to 12-week double-blind treatment with fluvastatin XL 80 mg once daily or fluvastatin IR 40 mg twice daily.. (1) There were 218 patients enrolled in each group. At the study endpoint, no statistical difference was found in the mean percent change from baseline for LDL-C with -8.69% [from (3.504 ± 0.060) mmol/L to (3.153 ± 0.065) mmol/L] in the fluvastatin XL group and -7.89% [from (3.491 ± 0.050) mmol/L to (3.181 ± 0.060) mmol/L] in the fluvastatin IR group (P > 0.05). The 95%CI for difference between the two groups in adjusted mean percent change from baseline was (-4.70%-3.09%), which was within the pre-specified non-inferiority margin. In the fluvastatin XL group, the proportion of patients with moderate cardiovascular (CV) risk and high CV risk achieving their LDL-C treatment goals at endpoint was 50.0% and 31.5% respectively, while the proportion was 42.5% and 24.5% respectively in the fluvastatin IR group. No significant difference was found between the two groups in the proportion of patients who reached their lipid goals and the changes from baseline with other lipid parameters. (2) Similar safety profiles were observed in the two treatment groups, with 21.1% adverse event (AE) (8.3% study-drug related AE) in the fluvastatin XL group and 17.0% AE (6.3% study-drug related AE) in the fluvastatin IR group.. The efficacy of fluvastatin XL 80 mg once daily is comparable to fluvastatin IR 40 mg twice daily in Chinese hyperlipidemic patients with moderate or high cardiovascular risk and both treatments are safe and well-tolerated.

Topics: Cardiovascular Diseases; Double-Blind Method; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hyperlipidemias; Indoles; Lipids; Risk Factors; Tablets

The long-term event monitoring (LEM) study evaluated the lipid-lowering efficacy and safety of fluvastatin in Japanese patients with hypercholesterolemia. The present sub-analysis focused on the impact of risk factors on event prevention.. In the LEM study, patients (n=21,139) who started fluvastatin between 2000/4/1 and 2002/3/31 in Japan were prospectively registered and followed up for 3 years (secondary prevention cohort) or 5 years (primary prevention cohort).. Of the patients registered, 19,084 were included in this sub-analysis. The secondary prevention group, demonstrated 8.27- and 2.89-fold higher incidence in cardiac events and cerebral events, respectively compared with the primary prevention group (P < 0.001). Complications of cerebrovascular disease demonstrated a 2.22- and 5.29-fold higher incidence in cardiac events and cerebral events (P < 0.01 and P < 0.001, respectively). Presence of diabetes mellitus (DM) in patients without complication significantly increased the incidence in both cardiac events (2.37) and cerebral events (2.15) as compared with non-DM patients for primary prevention (P < 0.001 and P < 0.01, respectively). For the secondary prevention, DM patients with complication of cardiac disease showed a significantly higher incidence in both cardiac events (1.59) and cerebral events (3.79) compared with non-DM patients (P < 0.05 and P < 0.01, respectively). In contrast, DM patients with complications of cerebrovascular disease showed a significantly higher incidence in cerebral events (2.58, P < 0.05), but not cardiac events compared with non-DM patients. Similarly, the presence of hypertension significantly increased the incidence in both cardiac (1.64) and cerebral events (1.81) for primary prevention (P < 0.01 and P < 0.05, respectively). For secondary prevention, hypertension in patients with complication of cardiac or cerebrovascular disease did not affect incidence in both cardiac and cerebral events. In the patients without complication, high triglycerides and low high density lipoprotein cholesterol (HDL-C), but not low density lipoprotein cholesterol (LDL-C), increased cerebral events, while only LDL-C significantly increased cardiac events. For secondary prevention, high triglycerides or low HDL-C, but not LDL-C, significantly increased the relative risk of cardiac events in the patients with complication of cardiac disease.. The LEM study, a large-scale prospective study of long-term fluvastatin treatment for hypercholesterolemia in Japanese patients, demonstrated high impact of complications such as DM and hypertension as well as high triglycerides or low HDL-C on cardiac and cerebral events. After long-term statin treatment, the control of other factors rather than LDL-C alone might be important to avoid vascular events.

Topics: Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Cohort Studies; Diabetes Mellitus; Drug Monitoring; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Indoles; Japan; Male; Middle Aged; Primary Prevention; Prospective Studies; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome

In patients with chronic kidney disease, vascular calcification contributes to increased cardiovascular (CV) morbidity and mortality. CV risk remains high after successful renal transplantation. Osteoprotegerin (OPG) is a glycoprotein, involved in the regulation of the vascular calcification process. Previous studies have shown that elevated OPG is predictive of mortality in high-risk populations. The aim of this study was to investigate the prognostic value of OPG for graft function, CV events and all-cause death, in a large transplant cohort.. OPG was measured at baseline in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) study, a randomized placebo-controlled intervention study comparing fluvastatin and placebo. Patients were followed for 6.7 years with evaluation of pre-specified end points, graft loss, graft function, CV events and death.. OPG was analysed in 1889 renal transplant recipients, with a mean value of 4.69 ± 1.85 pg/L. The number of renal and CV events increased by quartiles of OPG. In the multivariate analysis, OPG in the fourth as compared to first quartile was an independent predictor of graft failure or doubling of serum creatinine [hazard ratio (HR) 2.20 (1.56-3.11), P < 0.001], major CV events [HR 2.40 (1.58-3.64), P < 0.001], cardiac mortality [HR 2.80 (1.32-5.94), P = 0.007] and all-cause mortality [HR 2.31 (1.53-3.49), P < 0.001].. In a large cohort of kidney transplant patients with long-term follow-up, OPG was independently associated with renal events, CV events and mortality.

Topics: Adult; Aged; Anticholesteremic Agents; Biomarkers; Cardiovascular Diseases; Creatinine; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Graft Rejection; Humans; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Osteoprotegerin; Prognosis; Risk Factors; Survival Rate; Vascular Calcification

Adverse cardiac events are common after vascular surgery. We hypothesized that perioperative statin therapy would improve postoperative outcomes.. In this double-blind, placebo-controlled trial, we randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery. Lipid, interleukin-6, and C-reactive protein levels were measured at the time of randomization and before surgery. The primary end point was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary end point was the composite of death from cardiovascular causes and myocardial infarction.. A total of 250 patients were assigned to fluvastatin, and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6, and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group. Postoperative myocardial ischemia occurred in 27 patients (10.8%) in the fluvastatin group and in 47 (19.0%) in the placebo group (hazard ratio, 0.55; 95% confidence interval [CI], 0.34 to 0.88; P=0.01). Death from cardiovascular causes or myocardial infarction occurred in 12 patients (4.8%) in the fluvastatin group and 25 patients (10.1%) in the placebo group (hazard ratio, 0.47; 95% CI, 0.24 to 0.94; P=0.03). Fluvastatin therapy was not associated with a significant increase in the rate of adverse events.. In patients undergoing vascular surgery, perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome. (Current Controlled Trials number, ISRCTN83738615.)

Topics: Adrenergic beta-Antagonists; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Double-Blind Method; Electrocardiography; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Interleukin-6; Kaplan-Meier Estimate; Myocardial Ischemia; Perioperative Care; Postoperative Period; Troponin T; Vascular Surgical Procedures

The Assessment of Lescol in Renal Transplantation clinical trial demonstrated the efficacy of fluvastatin in reducing cardiovascular (CV) disease in renal transplant recipients. The study included a voluntary pharmacogenetic component, enrolling 1,404 patients, which allowed association testing of baseline measures and longitudinal analysis of the 707 fluvastatin-treated and 697 placebo-treated individuals. A candidate gene approach, examining 42 polymorphisms in 18 genes, was used to test for association between selected polymorphisms and major adverse cardiac events, graft failure, change in LDL and HDL cholesterol, and baseline LDL and HDL cholesterol. Reported associations between cholesteryl ester transfer protein (CETP) and baseline HDL cholesterol were replicated, with four previously implicated single nucleotide polymorphisms significantly associated in males and one in females; tests of reported associations between CETP and CV disease yielded varying results. We found no evidence for genetic factors affecting fluvastatin response. Polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) previously reported to affect the efficacy of pravastatin did not show a similar effect on the reduction of LDL cholesterol by fluvastatin.

Topics: Adult; Aged; Cardiovascular Diseases; Cholesterol Ester Transfer Proteins; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl CoA Reductases; Indoles; Kidney Transplantation; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic

The postprandial state is critical in atherogenesis. The aims of this study were to study the postprandial change of plasma high-sensitivity C-reactive protein (hsCRP) concentrations in patients at high risk for cardiovascular events, and to explore the influence of fluvastatin on hsCRP concentration.. Forty-three patients at high risk for cardiovascular events and 15 healthy controls participated in this study. All participants received an oral high-fat meal (800 calories; 50 g fat) at baseline. Blood samples were drawn at 0 and 4 h to measure the plasma concentrations of triglyceride, total cholesterol, low-density and high-density lipoprotein cholesterol and hsCRP. Then patients at high risk were randomly divided into two groups to accept fluvastatin (40 mg/day) (fluvastatin group, n=22) or placebo (placebo group, n=21). One week later, the high-fat meals were repeated and plasma samples were collected again.. The postprandial plasma triglyceride concentrations increased in all participants, whereas the postprandial plasma hsCRP concentrations increased significantly only in patients at high risk (P<0.05), but not in healthy controls. After 1 week, the fasting or postprandial plasma lipid levels and hsCRP concentrations did not significantly change in the placebo group compared with the levels at baseline, whereas the postprandial plasma triglyceride and hsCRP concentrations significantly decreased in the fluvastatin group. The reduction of plasma hsCRP concentration was not related to the change of plasma triglyceride concentration.. Fluvastatin effectively reduced postprandial plasma hsCRP concentrations in patients at high risk for cardiovascular events in a very short period of time.

Topics: Aged; Anticholesteremic Agents; C-Reactive Protein; Cardiovascular Diseases; Dietary Fats; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Indoles; Male; Middle Aged; Postprandial Period; Risk Factors; Triglycerides

Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease. Traditional and nontraditional risk factors for cardiovascular disease are prevalent in renal patients. In renal-transplant recipients, immunosuppressive therapy can be nephrotoxic and aggravate cardiovascular disease risk factors. Renal dysfunction has been established as a risk factor for cardiovascular disease and mortality in different populations. We evaluated the effects of baseline renal-transplant function on mortality and cardiovascular and renal endpoints in 1,052 placebo-treated patients of the Assessment of Lescol in Renal Transplantation trial.. All renal-transplant recipients were on cyclosporine-based immunosuppressive therapy. Follow-up was 5 to 6 years, and endpoints included cardiac death, noncardiovascular death, all-cause mortality, major adverse cardiac event (MACE), stroke, nonfatal myocardial infarction, and graft loss.. Baseline serum creatinine was strongly and independently associated with increased cardiac, noncardiovascular, and all-cause mortality, as well as MACE and graft loss. Serum creatinine was not a risk factor for stroke or nonfatal myocardial infarction.. Elevated baseline serum creatinine in renal-transplant recipients is a strong and independent risk factor for all-cause, noncardiovascular and cardiac mortality, MACE, and graft loss.

Topics: Adult; Antioxidants; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluvastatin; Heart Diseases; Humans; Indoles; Kidney; Kidney Transplantation; Placebos; Risk Factors

Renal transplant recipients (RTR) have an increased risk of premature cardiovascular disease. The ALERT study is the first trial to evaluate the effect of statin therapy on cardiac outcomes following renal transplantation. Patients initially randomized to fluvastatin or placebo in the 5-6 year ALERT study were offered open-label fluvastatin XL 80 mg/day in a 2-year extension to the original study. The primary endpoint was time to first major adverse cardiac event (MACE). Of 1787 patients who completed ALERT, 1652 (92%) were followed in the extension. Mean total follow-up was 6.7 years. Mean LDL-cholesterol was 98 mg/dL (2.5 mmol/L) at last follow-up compared to a pre-study level of 159 mg/dL (4.1 mmol/L). Patients randomized to fluvastatin had a reduced risk of MACE (hazards ratio [HR] 0.79, 95% CI 0.63-0.99, p = 0.036), and a 29% reduction in cardiac death or definite non-fatal MI (HR 0.71, 95% CI 0.55-0.93, p = 0.014). Total mortality and graft loss did not differ significantly between groups. Fluvastatin produces a safe and effective reduction in LDL-cholesterol associated with reduced risk of MACE in RTR. The lipid-lowering and cardiovascular benefits of fluvastatin are comparable to those of statins in other patient groups, and support use of fluvastatin in RTR.

Topics: Adult; Cardiovascular Diseases; Delayed-Action Preparations; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Transplantation; Lipids; Male; Middle Aged; Postoperative Complications; Risk Factors; Treatment Outcome

To investigate the effect on risk of major adverse cardiac events (MACE) of lipid lowering treatment with fluvastatin 80 mg/day after a first percutaneous coronary intervention in patients with stable and unstable angina.. This prespecified subgroup analysis of the LIPS (Lescol intervention prevention study) analysed 1658 patients with documented diagnosis; 824 had unstable angina (417 randomly assigned to fluvastatin, 407 to placebo) and 834 had stable angina (including silent ischaemia; fluvastatin, 418; placebo, 416). Median follow up was 3.9 years. There was no significant effect of anginal status on long term risk of MACE. Fluvastatin treatment reduced the risk of MACE by 28% compared with placebo (p = 0.03) among patients with unstable angina, with no difference between patients with stable and patients with unstable angina (relative risk 1.07, 95% confidence interval 0.87 to 1.30, p = 0.53). Fluvastatin reduced coronary atherosclerotic events (MACE excluding restenosis) by 36% (p = 0.006) among patients with unstable angina and 31% (p = 0.02) among patients with stable angina. Fluvastatin caused similar reductions in total cholesterol and low density lipoprotein cholesterol concentrations in both patient groups.. Treatment with fluvastatin 80 mg/day produced significant reductions in MACE and coronary atherosclerotic events after percutaneous coronary intervention in patients with average cholesterol concentrations. The beneficial effects of fluvastatin are observed in patients with unstable or stable angina alike.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypolipidemic Agents; Indoles; Male; Middle Aged; Postoperative Period; Prospective Studies

Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population.. We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat.. After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups.. Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.

Topics: Adult; Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Drug Interactions; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Immunosuppressive Agents; Indoles; Kidney Transplantation; Male; Middle Aged; Placebos; Risk Factors

In the main publication for LIPS (Lescol Intervention Prevention Study), a 22% relative risk (RR) reduction for major adverse cardiac events (MACE) was found among those who used fluvastatin after a successful first percutaneous coronary intervention (PCI). However, intent-to-treat (ITT) analysis of clinical studies generally provides an observed treatment effect that is likely to underestimate what the treatment effect would be if compliance were perfect, because compliance in a clinical trial is invariably <100% during long-term follow-up.. The aim of this study was to analyze the relationship between compliance and treatment effect in LIPS.. In LIPS, patients who had undergone a successful first PCI were randomized to receive fluvastatin 40 mg BID or placebo BID for 3 to 5 years. The primary end point was survival time free of MACE (ie, cardiac death, nonfatal myocardial infarction, or reintervention procedure), and a Cox proportional hazards regression model with time-dependent covariates was used to predict the effect that fluvastatin would have had if trial medication had been continued. Logistic regression was used to determine factors influencing discontinuation of trial medication.. A total of 1677 patients were enrolled in LIPS: 844 in the fluvastatin group and 833 in the placebo group. In the fluvastatin group, 294 patients (34.8%) discontinued taking trial medication and 73 (8.6%) switched to another lipid-lowering medication, compared with 353 (42.4%) and 187 (22.4%) patients in the placebo group, respectively. The risk factor-adjusted RR of MACE with fluvastatin treatment was 0.74 (P = 0.004; 95% CI, 0.61-0.91). When also adjusted for noncompliance, the RR for fluvastatin versus placebo was 0.68 (P = 0.002; 95% CI, 0.53-0.86). Discontinuing fluvastatin without switching to another lipid-lowering medication increased the risk of MACE compared with that of patients who stayed on fluvastatin (RR = 2.27; P < 0.001; 95% CI, 1.60-3.23) and the increase in the risk of MACE was greater than that associated with discontinuing placebo (P = 0.032).. The present study found a 32% RR reduction for experiencing MACE during fluvastatin treatment after a successful PCI in LIPS, when analysis allowed for noncompliance. This suggests that the ITT analysis discussed in the main LIPS publication underestimated the benefit of fluvastatin treatment. Our survival model also provided tentative evidence that discontinuing lipid-lowering medication might lead to a potentially harmful rebound effect in this patient group.

Topics: Adult; Aged; Angioplasty, Balloon; Anticholesteremic Agents; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Indoles; Male; Middle Aged; Regression Analysis; Retrospective Studies; Risk Factors; Time Factors; Treatment Refusal

Statins reduce cardiovascular events and progression of carotid intima-media thickness (IMT). beta-Blockers are also known to reduce cardiovascular events, but less is known about their effects on carotid IMT.. We conducted a randomized, double-blind, placebo-controlled, single-center trial to compare the effects of low-dose metoprolol CR/XL (25 mg once daily) and fluvastatin (40 mg once daily) on the progression of carotid IMT during 36 months of treatment in 793 subjects who had carotid plaque but no symptoms of carotid artery disease. Changes in mean IMT in the common carotid artery and maximal IMT in the bulb were the main outcome variables. Death and cardiovascular events were monitored. Progression of IMT(max) in the carotid bulb at both 18 and 36 months was reduced by metoprolol CR/XL (-0.058 mm/y; 95% CI, -0.094 to -0.023; P=0.004; and -0.023 mm/y; 95% CI, -0.044 to -0.003; P=0.014, respectively). Incidence of cardiovascular events tended to be lower in metoprolol CR/XL-treated patients (5 versus 13 patients, P=0.055). Rate of IMT(mean) progression in the common carotid at 36 months was reduced by fluvastatin (-0.009 mm/y; 95% CI, -0.015 to -0.003; P=0.002). Women in the fluvastatin group had increased frequency of transiently high liver enzymes.. This is the first randomized trial to show that a beta-blocker can reduce the rate of progression of carotid IMT in clinically healthy, symptom-free subjects with carotid plaque. This suggests that beta-blockers may have a favorable effect on atherosclerosis development.

Topics: Aged; Anticholesteremic Agents; Antihypertensive Agents; Arteriosclerosis; Blood Pressure; Cardiovascular Diseases; Carotid Arteries; Cholesterol; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Heart Rate; Humans; Incidence; Indoles; Male; Metoprolol; Middle Aged; Random Allocation; Tunica Intima

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.. 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.. 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).. 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.

Topics: Adult; Aged; Anticholesteremic Agents; Cardiovascular Diseases; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Research Design; Risk Factors; Statistics, Nonparametric; Treatment Outcome

To investigate how statins reduce cardiovascular mortality in patients with type 2 diabetes (T2DM) in a dose-, class-, and use intensity-dependent manner.. We used an inverse probability of treatment-weighted Cox hazards model, with statin use status as a time-dependent variable, to estimate the effects of statin use on cardiovascular mortality.. Adjusted hazard ratio [aHR; 95% confidence interval (CI)] for cardiovascular mortality was 0.41 (0.39-0.42). Compared with nonusers, pitavastatin, pravastatin, simvastatin, rosuvastatin, atorvastatin, fluvastatin, and lovastatin users demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.11 (0.06, 0.22), 0.35 (0.32, 0.39), 0.36 (0.34, 0.38), 0.39 (0.36, 0.41), 0.42 (0.40, 0.44), 0.46 (0.43, 0.49), and 0.52 (0.48, 0.56), respectively]. In Q1, Q2, Q3, and Q4 of cDDD-year, our multivariate analysis demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.63 (0.6, 0.65), 0.44 (0.42, 0.46), 0.33 (0.31, 0.35), and 0.17 (0.16, 0.19), respectively; P for trend < 0.0001]. The optimal statin dose daily was 0.86 DDD, with the lowest aHR for cardiovascular mortality of 0.43.. Persistent statin use can reduce cardiovascular mortality in patients with T2DM; in particular, the higher is the cDDD-year of statin, the lower is the cardiovascular mortality. The optimal statin dose daily was 0.86 DDD. The priority of protective effects on mortality are pitavastatin, rosuvastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and lovastatin for the statin users compared with non-statin users.

Topics: Atorvastatin; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Pravastatin; Primary Prevention; Rosuvastatin Calcium; Simvastatin

Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF.. This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use.. Among Africans with HF, statin treatment was associated with significant reduction in mortality.

Topics: Aged; Atorvastatin; Atrial Fibrillation; Black People; Cardiomyopathy, Dilated; Cardiovascular Diseases; Cause of Death; Comorbidity; Coronary Artery Disease; Diabetes Mellitus; Fatty Acids, Monounsaturated; Fluvastatin; Ghana; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Indoles; Kaplan-Meier Estimate; Longitudinal Studies; Middle Aged; Mortality; Multivariate Analysis; Probability; Proportional Hazards Models; Renal Insufficiency, Chronic; Retrospective Studies; Rosuvastatin Calcium; Simvastatin; Treatment Outcome

Statins may have beneficial vascular effects in systemic lupus erythematosus (SLE) beyond their cholesterol-lowering action, although the mechanisms involved are not completely understood. We investigated potential mechanisms involved in the efficacy of fluvastatin in preventing atherothrombosis in SLE.. Eighty-five patients with SLE and 62 healthy donors were included in the study. Selected patients (n=27) received 20 mg/day fluvastatin for 1 month. Blood samples were obtained before the start and at the end of treatment. Monocytes from five patients were treated in vitro with fluvastatin.. Increased prothrombotic and inflammatory variables were found in patients with SLE. SLE monocytes displayed altered mitochondrial membrane potential and increased oxidative stress. Correlation and association analyses demonstrated a complex interplay among autoimmunity, oxidative stress, inflammation and increased risk of atherothrombosis in SLE. Fluvastatin treatment of patients for 1 month reduced the SLE Disease Activity Index and lipid levels, oxidative status and vascular inflammation. Array studies on monocytes demonstrated differential expression in 799 genes after fluvastatin treatment. Novel target genes and pathways modulated by fluvastatin were uncovered, including gene networks involved in cholesterol and lipid metabolism, inflammation, oxidative stress and mitochondrial activity. Electron microscopy analysis showed increased density volume of mitochondria in monocytes from fluvastatin-treated patients, who also displayed higher expression of genes involved in mitochondrial biogenesis. In vitro treatment of SLE monocytes confirmed the results obtained in the in vivo study.. Our overall data suggest that fluvastatin improves the impairment of a redox-sensitive pathway involved in processes that collectively orchestrate the pathophysiology of atherothrombosis in SLE.

Topics: Adult; Atherosclerosis; Cardiovascular Diseases; Case-Control Studies; Cells, Cultured; Comorbidity; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; In Vitro Techniques; Indoles; Lupus Erythematosus, Systemic; Male; Middle Aged; Monocytes; Oxidation-Reduction; Oxidative Stress; Signal Transduction; Treatment Outcome

This long-term event monitoring (LEM) study was designed to evaluate the long-term lipid-lowering efficacy and safety of fluvastatin (Lochol®, Novartis A.G.) along with the incidence of cardiac and other events, and safety of fluvastatin in Japanese patients with hypercholesterolemia.. Patients (n = 21,139) who started fluvastatin between April 1, 2000 and March 31, 2002, across 2563 centers in Japan were prospectively registered and followed up for 3 years (secondary prevention cohort) or 5 years (primary prevention cohort).. Of the patients registered, 19,084 were included in this analysis. Levels of low-density lipoprotein-cholesterol (LDL-C) and total cholesterol (TC) decreased significantly in the primary (-27.1% and -18.8%) and secondary (-25.3% and -18.4%) prevention cohorts. Reductions in LDL-C (-22.1 vs. -18.2%, p < 0.0001) and TC (-16.1 vs. -13.1%, p < 0.0001) levels were significantly greater among patients aged ≥ 65 than < 65 years old. Overall, 1.7% (146/8563) and 1.1% (93/8563) of patients aged ≥ 65 years old experienced confirmed cardiac and cerebral events, compared with 1.1% (112/10,517) and 0.3% (28/10,517) of patients aged < 65 years old (p = 0.0002 and < 0.0001, respectively). Incidence of cardiac and cerebral events was lowest in patients aged < 65 years old in the primary prevention cohort and highest among patients aged ≥ 65 years old in the secondary prevention cohort. Adverse events were reported in 7.9% (1501/19,084) of patients.. This large-scale, prospective, uncontrolled study confirmed the lipid-lowering efficacy and safety of long-term fluvastatin treatment for hypercholesterolemia in Japanese patients aged ≥ 65 years old. The higher incidence of cardiac and cerebral events in patients aged ≥ 65 years old in the secondary prevention cohort reflects a high-risk clinical profile with multiple classic risk factors warranting multifactorial interventions.

Topics: Age Factors; Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Cholesterol; Cholesterol, LDL; Drug Monitoring; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Indoles; Male; Middle Aged; Prospective Studies

Topics: Anticholesteremic Agents; Azetidines; Cardiovascular Diseases; Cholesterol, LDL; Drug Therapy, Combination; Ezetimibe; Fatty Acids, Monounsaturated; Fenofibrate; Fluvastatin; Humans; Hypolipidemic Agents; Indoles; Metabolic Syndrome; Simvastatin

Topics: Cardiovascular Diseases; Electrocardiography; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Myocardial Ischemia; Postoperative Period; Vascular Surgical Procedures

To compare change in low-density lipoprotein cholesterol (LDL-C) levels and National Cholesterol Education Program (NCEP) Adult Treatment Panel III LDL-C goal attainment in diabetic patients treated with rosuvastatin versus other statins in a large, managed care health plan.. This retrospective cohort analysis used medical and pharmacy claims linked to laboratory results from a commercial/MedicareAdvantage health plan. Study participants were >or= 18 years of age, had a diagnosis of diabetes, were newly treated with statins from 8/1/03 to 2/28/05, and were considered at high risk for cardiovascular events as defined by NCEP guidelines. Subjects were continuously enrolled for 12 months pre-index and >or= 30 days post-index, with variable follow-up until therapy discontinuation or end of health plan eligibility.. Change in LDL-C from baseline, and attainment of NCEP LDL-C goal among patients not at goal before starting therapy.. A total of 3337 adult patients with diabetes were identified with new use of statin therapy during the identification period. A total of 9% (n = 301) started on rosuvastatin, 49.4% (n = 1,649) on atorvastatin, 20.7% (n = 690) on simvastatin, 7.0% (n = 234) on pravastatin, 11.7% (n = 391) on lovastatin and 2.2% (n = 72) on fluvastatin. After controlling for covariates, rosuvastatin patients experienced a significantly greater decrease in LDL-C from baseline (38.7%) than patients taking atorvastatin (34.2%) (p = 0.05), simvastatin (31.5%), pravastatin (24.2%), fluvastatin (26.3%) or lovastatin (24.9%) (p < 0.0001). Rosuvastatin users were significantly more likely to attain LDL-C goal than those taking the other statins (odds ratio: 0.44, 0.28, 0.14, 0.14, 0.19, respectively; p < 0.001). Predicted percent attaining goal was significantly greater for those taking rosuvastatin (87.3%) than for those taking atorvastatin (76.9%), simvastatin (68.7%), pravastatin (55.0%), lovastatin (55.3%) or fluvastatin (61.3%) (p < 0.001).. For diabetic patients, rosuvastatin is more effective at reducing LDL-C levels and attaining NCEP ATP III LDL-C goal than other statins in real-world clinical practice.

Topics: Adult; Aged; Atorvastatin; Cardiovascular Diseases; Cholesterol, LDL; Cohort Studies; Diabetes Complications; Fatty Acids, Monounsaturated; Female; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lovastatin; Male; Managed Care Programs; Middle Aged; Practice Guidelines as Topic; Pravastatin; Pyrimidines; Pyrroles; Retrospective Studies; Risk Factors; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Treatment Outcome; United States

Statins reduce lipid levels, inflammation and cardiovascular events in patients with coronary artery disease; CKD patients show increased risk of cardiovascular and increased plasma levels of IL-6 and IL-8.. To evaluate the in vitro effect of simvastatin (S) or fluvastatin (F) on the lipopolysaccharide (LPS) stimulated secretion of IL-6 and IL-8 from monocytes of chronic kidney disease patients (CKD) in K-DOQI stages 3-5.. Monocytes enriched peripheral blood (PBMC) from 28 CKD (15 in K-DOQI stages 3-4, Group I, and 13 in K-DOQI stage 5 on hemodialysis, Group II) and 10 healthy subjects (HS), were isolated by Ficoll-gradient centrifugation. Cells were incubated with LPS 100 ng/ml or with LPS plus increasing doses of statins (from 10(-6) to 10(-8) M ) for 24 h. Surnatant IL-6 and IL-8 concentrations were determined by EIA.. Basally the mean concentration of IL-6 and IL-8 was higher in patients than in HS and in Group II than in Group I (IL6: HS 285 +/- 77 pg/ml, Group I 365 +/- 178 pg/ml, Group II 520 +/- 139 pg/ml- IL8 HS 180 +/- 75 pg/ml, Group I 1722 +/- 582 pg/ml, Group II 4400 +/- 1935 pg/ml). After addition of LPS the mean concentration of IL-6 and IL-8 increased in all groups (IL6: HS 1740 +/- 178 pg/ml, Group I 3754 +/- 672 pg/ml, Group II 4800 +/- 967 pg/ml; IL8: HS 450+/-132 pg/ml, Group I 9700+/-2837 pg/ml, Group II 11608 +/- 2316 pg/ml). After the addition of LPS plus increasing doses of S or F from 10(-10) to 10(-6) M, a significantly lower cytokine concentration compared to the data after LPS alone was observed (IL6: HS 45%, Group I 75%, Group II 50%; IL8: HS 100%, Group I 65%, Group II 35%).. These data confirm that cytokine release is increased in CKD patients and that is highest in the most severe patients. Furthermore they suggest that fluvastatin or simvastatin can be used in order to reduce the high cardiovascular risk.

Topics: Cardiovascular Diseases; Cells, Cultured; Chronic Disease; Cytokines; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Interleukin-6; Interleukin-8; Kidney Diseases; Lipopolysaccharides; Monocytes; Simvastatin

To investigate the effect of statins on vascular dysfunction in rat adjuvant-induced arthritis (AIA).. Fluvastatin (5 mg/kg/day) was administered orally to rats with AIA, for 21 days after the onset of arthritis. The vasodilatory response to acetylcholine of aortic rings isolated from rats with AIA that were not treated or were treated with fluvastatin and from normal rats was determined. The amounts of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine in aortas were measured by Western blotting. In vitro and in situ superoxide production in aortas was evaluated based on fluorogenic oxidation of dihydroethidium to ethidium. Expression of NAD(P)H components and endothelial nitric oxide synthase (eNOS) in aortas was examined by real-time reverse transcriptase-polymerase chain reaction and Western blotting. Serum levels of tetrahydrobiopterin, a critical eNOS cofactor, were determined by high-performance liquid chromatography.. Fluvastatin reversed endothelial dysfunction in AIA without affecting the clinical severity of arthritis or serum cholesterol concentration. Fluvastatin reduced the amounts of HNE and nitrotyrosine in the aorta, and the levels of superoxide expressed in endothelial cells and smooth muscle cells in the tissue, in rats with AIA. NADH- or L-arginine-induced superoxide production was not observed in the aortic samples from fluvastatin-treated rats with AIA. Fluvastatin decreased the levels of expression of messenger RNA for p22phox, a NAD(P)H oxidase component, in the aortas of rats with AIA, but did not affect the expression of eNOS. Serum levels of tetrahydrobiopterin were significantly reduced in rats with AIA, and were increased by administration of fluvastatin.. Our findings demonstrate that fluvastatin has potent vascular protective effects in AIA and provide additional scientific rationale for the use of statins to reduce cardiovascular mortality in patients with rheumatoid arthritis.

Topics: Acetylcholine; Animals; Anticholesteremic Agents; Aorta, Thoracic; Arthritis, Experimental; Arthritis, Rheumatoid; Biopterins; Cardiovascular Diseases; Disease Models, Animal; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fluvastatin; Indoles; Male; NADPH Oxidases; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Rats, Inbred Lew; Superoxides; Vasodilation; Vasodilator Agents

Renal transplant recipients (RTR) mainly die of premature cardiovascular disease. Traditional cardiovascular disease risk factors are prevalent in RTR. Additionally, non-traditional risk factors seem to contribute to the high risk. The impact of renal dysfunction was compared with traditional risk factors for cardiovascular morbidity and mortality in 1052 placebo-treated patients of the ALERT trial.. All patients were on cyclosporine-based immunosuppressive therapy, follow-up was 5-6 years and captured endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke.. A calculated 84 micromol/l increase in serum creatinine was needed to double the risk for cardiac death, an increase of 104 micromol/l to double the risk for non-cardiovascular death and an increase of 92 micromol/l to double the risk for all-cause mortality. MACE risk was doubled if serum creatinine was elevated by 141 micromol/l, age was increased by 23 years, or LDL-cholesterol by 2 mmol/l. Diabetes increased the incidences of cardiac death, all-cause mortality, MACE, stroke and non-fatal MI. A serum creatinine increase of approximately 130 micromol/l, or approximately 20 years increase in age was calculated as similar in risk for cardiac death, all-cause mortality and MACE, and comparable to risk of diabetes in RTR.. An increase in serum creatinine of 80-100 micromol/l doubles the risk for cardiac death, non-cardiovascular death and all-cause mortality in RTR. An increase of 130 micromol/l in serum creatinine or approximately 20 years increase in age is comparable to risk of diabetes.

Topics: Adult; Age Factors; Anticholesteremic Agents; Cardiovascular Diseases; Cause of Death; Cholesterol, LDL; Comorbidity; Creatinine; Delayed Graft Function; Diabetes Complications; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hypercholesterolemia; Immunosuppressive Agents; Indoles; Kidney Transplantation; Male; Middle Aged; Mortality; Myocardial Infarction; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke

Topics: Cardiovascular Diseases; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fish Oils; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Male; Risk Factors

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Diseases; Kidney Transplantation; Quality Control; Risk Factors

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Indoles; Kidney Diseases; Kidney Transplantation; Quality Control; Risk Factors

Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population.. We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression.. The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P < 0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P < 0.0001).. This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.

Topics: Adult; Aged; Cardiovascular Diseases; Creatinine; Death, Sudden, Cardiac; Diabetes Mellitus; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Immunosuppressive Agents; Indoles; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mortality; Myocardial Infarction; Obesity; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Survival Analysis

Statins have been shown to significantly reduce morbidity and mortality both in patients with coronary artery disease and in those with dyslipidemia when they are taken regularly. Middle-aged patients have the highest level of forecasting benefit, and little is known about the persistence rate of these therapies in a real-life setting.Objective. To evaluate the persistence rate of middle-aged patients initiating statin therapy as well as its relation to patients' demographic and clinical characteristics.. A cohort of 25,733 patients was reconstructed from prescription data recorded in the Régie de l'assurance maladie du Québec administrative database. All patients aged 50-64 years old who received at least one statin prescription between January 1, 1998 and December 31, 2000 for a new intention of treatment for dyslipidemia were included in the cohort and followed up until June 30, 2001. The date of the first prescription of statin was defined as the index date. The cumulative persistence rate was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of ceasing statins after adjustment.. Mean age of patients initiating statin agents was 58 years; 39%were male, 24% received social assistance, 19% had diabetes, 30% had hypertension and 11% had a respiratory disease at cohort entry. Persistence with statin therapy fell to 67% in the first 6 months after treatment and continued to decline over the next 3 years to 39%. At 3 years, persistence varied significantly with statin agents. After controlling for individual patients' demographic and clinical characteristics, we found that patients who were prescribed fluvastatin, lovastatin and atorvastatin had a higher rate of cessation than those on simvastatin and pravastatin. The adjusted rate ratio of ceasing statin agents in patients with other risk factors of cardiovascular disease, such as diabetes (HR: 0.78; 0.75-0.82) or hypertension (HR: 0.72; 0.69-0.74), demonstrated a lower cessation rate. We observed lower persistence in patients who used the greatest number of pharmacies and prescribing physicians.. This analysis indicates that barriers to persistence occur early in the therapeutic course. Overall persistence with statins is low, particularly among patients with few other cardiovascular risk factors.

Topics: Atorvastatin; Cardiovascular Diseases; Drug Prescriptions; Dyslipidemias; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lovastatin; Male; Middle Aged; Patient Compliance; Pyrroles; Regression Analysis; Time Factors

Many studies have shown differences between statins based on surrogate endpoints, but few have studied differences in reaching clinical endpoints. This study compares the risk of cardiovascular and cerebrovascular events between atorvastatin users and other statin users in daily general practice.. A cohort study was performed in the Integrated Primary Care Information project database, a longitudinal general practice research database with electronic patient records of more than 500,000 individuals in The Netherlands. All new statin users in the period 1st September 1999 to 31st December 2002 were included. Multivariate Cox-regression analysis was used to compare the occurrence of the primary endpoint between atorvastatin users and other statin users.. The primary endpoint was the composite outcome of fatal or non-fatal myocardial infarction, admission for unstable angina pectoris, fatal or non-fatal cerebrovascular accidents, or transient ischaemic events.. 3499 new statin users were identified, including 797 patients with a history of cardiovascular disease. 1341 persons started with simvastatin (38.3%), 1154 with atorvastatin (33.0%), 811 with pravastatin (23.2%) and 193 with other statins (5.5%). The median follow-up was 1.9 years. Two hundred and thirty three patients (6.7%) experienced a primary endpoint. Atorvastatin users had a significantly lower risk of cardiovascular and cerebrovascular events than users of other statins (relative risk [RR]: 0.70, 95% confidence interval [CI]: 0.55-0.96). The relative risks of atorvastatin users compared to simvastatin and pravastatin users individually were 0.70 (95% CI: 0.48-1.02) and 0.78 (95% CI: 0.52-1.16), respectively. The protective effect of atorvastatin was more pronounced in persons without a history of cardiovascular or cerebrovascular events.. Atorvastatin showed a more favourable effect on fatal and non-fatal cardiovascular and cerebrovascular events in the general population than other statins.

Topics: Adult; Aged; Atorvastatin; Cardiovascular Diseases; Cholesterol; Cohort Studies; Endpoint Determination; Family Practice; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Netherlands; Pravastatin; Pyridines; Pyrroles; Simvastatin; Treatment Outcome

This pooled analysis of 30 completed clinical trials assessed the efficacy and safety of fluvastatin in patients <65 (n = 8,037) and patients > or =65 years of age (n = 3,717). The results demonstrated that in patients > or =65 years of age, lipid changes with fluvastatin therapy are equivalent to or slightly better than those observed in patients <65 years of age. Treatment with fluvastatin produced a significantly lower incidence of major cardiovascular clinical end points (major adverse cardiac events [MACEs]) and an increase in the time to a first MACE in the older population. The incidence of adverse events, particularly those of concern with statin therapy, was similar between the placebo- and fluvastatin-treated patients and between the different age groups. In conclusion, data derived from the pooled analysis with fluvastatin demonstrate that cardiovascular events are reduced in older high-risk patients to a greater extent compared with younger patients. Furthermore, this pooled analysis supports the use of fluvastatin to lower cholesterol levels in older high-risk patients.

Topics: Age Factors; Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol; Databases, Factual; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Middle Aged; Randomized Controlled Trials as Topic; Safety

Topics: Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Kidney Transplantation; Postoperative Complications; Time Factors

Topics: Adrenergic beta-Antagonists; Adult; Bisoprolol; Cardiovascular Diseases; Drug Therapy, Combination; Elective Surgical Procedures; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Indoles; Intraoperative Complications; Myocardial Infarction; Perioperative Care; Postoperative Complications; Premedication; Proportional Hazards Models; Randomized Controlled Trials as Topic; Research Design; Risk Assessment

Topics: Anticholesteremic Agents; Canada; Cardiovascular Diseases; Drug Costs; Economics, Pharmaceutical; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Indoles; Pravastatin; Simvastatin

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

Topics: Aged; Anticholesteremic Agents; Blood Platelets; Cardiovascular Diseases; Cholesterol; Endothelin-1; Factor VII; Fatty Acids, Monounsaturated; Female; Fibrinogen; Fluvastatin; Humans; Hypercholesterolemia; Indoles; Male; Middle Aged; Neopterin; Nucleotides, Cyclic

We evaluated the use of combination therapy (ciprofibrate 100 mg or bezafibrate 400 mg plus fluvastatin 40 mg) in 23 patients (n = 13 in the ciprofibrate group) with established cardiovascular disease. Both treatments achieved a significant (P< or =0.01) decrease in the total cholesterol (TC) (32 and 21%), triglycerides (TG) (53 and 46%) and low-density lipoprotein (LDL) (36 and 26%) levels and the TC/high-density lipoprotein (HDL) (42 and 31%) and LDL/HDL (46 and 35%) ratios. HDL levels were increased (19% for both treatment groups), but this rise only achieved significance (P=0.01) in the ciprofibrate group. Although the two patient groups were not strictly matched, the reduction in serum TC and LDL levels was greater with ciprofibrate (32 and 36%, respectively; P< or =0.001) than with bezafibrate (21 and 26%, respectively; P< or =0.01). There was a significant reduction in plasma fibrinogen levels (36.4 and 13.5% in the ciprofibrate and bezafibrate group, respectively). None of the patients reported myalgia or had abnormal creatine kinase activity or liver function tests. Combination therapy is worth considering in high-risk patients because of the advantages associated with this option. Combination therapy is competitively priced when compared with high doses of statins. An end-point-based trial is needed.

Topics: Adult; Aged; Aged, 80 and over; Anticholesteremic Agents; Bezafibrate; Cardiovascular Diseases; Clofibric Acid; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fibric Acids; Fluvastatin; Humans; Hyperlipidemias; Hypolipidemic Agents; Indoles; Male; Middle Aged; Pilot Projects; Treatment Outcome

Topics: Cardiovascular Diseases; Cost-Benefit Analysis; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hypercholesterolemia; Indoles; Lovastatin; Pravastatin; Simvastatin