cerivastatin and Cardiovascular-Diseases

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 We also contacted authors of relevant papers regarding further published and unpublished work.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

To summarize recent findings on pharmacokinetics, pharmacodynamics, drug-drug interactions and influence of lifestyle heterogeneity on adverse events in cholesterol-lowering therapy. The prevention of cardiovascular disease is critically dependent on lipid-lowery therapy, including statins, cholesterol absorption inhibitors, fibrates and nicotinic acid. Statins are the most prescribed drugs in lipid lowering therapy with variability in response and almost one third of the patients do not meet their treatment goals. The severe adverse effects of treatment with cerivastatin stimulated the search for new genes and gene variations affecting pharmacokinetics, drug-drug interactions and pharmacodynamics. Moreover, instead of monotherapy, combined therapy of statins with ezetemibe and niacin was considered. This led to the identification of CD13, NPC1L1 and HM74A as new targets and CYP2C8 and glucuronidation enzymes as potential targets for drug-drug interactions. Moreover multiple polymorphic sites and pleiotrophic gene targets were reinvestigated in larger cohorts and the relevant pathogenetic factors start to evolve.. Statin therapy is widely used and well tolerated by the majority of patients. To further reduce potential adverse effects and to increase efficacy, combined therapy concepts with ezetimibe or niacin are underway.

Topics: Anticholesteremic Agents; Biological Transport; Cardiovascular Diseases; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Niacin; Pharmacogenetics; Pyridines

Hypertension and hypercholesterolemia are frequently associated, and their treatment is proven to reduce cardiovascular risk. Current guidelines on cardiovascular prevention strongly recommend treating both disorders. Unfortunately, the low treatment and control rates, combined with the high prevalence of both conditions, still contribute to the high burden of cardiovascular disease in Western countries. In the past 5 years, many studies evaluating the benefit of combined antihypertensive and lipid-lowering treatment on endothelial dysfunction, coronary atherosclerosis, hypertension control, and on primary and secondary prevention of cardiovascular events have been published. In this article, we discuss and critically evaluate the available evidence on the potential benefits of combined antihypertensive and lipid-lowering treatment.

Topics: Anticholesteremic Agents; Antihypertensive Agents; Arteriosclerosis; Cardiovascular Diseases; Comorbidity; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Nifedipine; Pyridines; Simvastatin

Topics: Animals; Arteriosclerosis; Cardiovascular Diseases; CCAAT-Enhancer-Binding Proteins; Cholesterol; Cholesterol, LDL; Coenzyme A Ligases; Diabetes Mellitus, Type 2; DNA-Binding Proteins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hydroxymethylglutaryl-CoA Synthase; Hyperlipidemias; Pravastatin; Pyridines; Randomized Controlled Trials as Topic; Sterol Regulatory Element Binding Protein 1; Transcription 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

Topics: Cardiovascular Diseases; Cholesterol; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Immunosuppressive Agents; Kidney Transplantation; Lipids; Lipoproteins; Male; Postoperative Complications; Pyridines; Risk Factors; Time Factors

Hyperlipidaemia is an important risk factor for cardiovascular disease in renal transplant recipients. The aim of this study was to test the efficacy and possible drug-drug interactions of the new HMG-CoA reductase inhibitors (statins) atorvastatin and cerivastatin in cyclosporin A (CsA)-treated renal transplant patients. Subjects and methods. Thirty patients with stable graft function and LDL cholesterol of 130 mg/dl were randomly assigned to active treatment groups (10 mg atorvastatin or 0.2 mg cerivastatin), or a control group. CsA blood trough levels were controlled on a weekly basis and adapted if they changed more than 25% from baseline values (100-150 ng/ml). Lipid levels and routine laboratory parameters before and after a treatment period of 3 months were compared.. In the group treated with cerivastatin no significant changes in CsA blood trough levels occurred (CsA 116+/-21 ng/ml vs 110+/-20 ng/ml). In contrast, in the group treated with atorvastatin, four of 10 patients had a rise in CsA blood trough levels of more than 25% within 7-14 days of starting therapy. In the remaining patients no significant changes in CsA drug levels occurred. After therapy with atorvastatin or cerivastatin, total cholesterol, LDL cholesterol, and triglycerides were significantly lower compared with baseline conditions. No changes of CsA or lipoprotein levels were present in the control group.. In our study population both statins were very effective in lowering elevated LDL cholesterol levels. Cerivastatin did not influence CsA blood trough levels, whereas atorvastatin increased CsA levels in four of 10 patients. Further research in a larger study is necessary in order to confirm these results and to investigate the possible reasons for this drug interaction.

Topics: Adult; Aged; Atorvastatin; Cardiovascular Diseases; Cyclosporine; Drug Interactions; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Pyridines; Pyrroles; Safety

Topics: Adult; Aged; Cardiovascular Diseases; China; Cholesterol, HDL; Ethnicity; Female; Humans; Male; Middle Aged; Pyridines; Risk Factors; Triglycerides

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

Topics: Cardiovascular Diseases; Fluorobenzenes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Pain; Pyridines; Pyrimidines; Rosuvastatin Calcium; Sulfonamides

Topics: Cardiovascular Diseases; Cholesterol; Coenzymes; Drug Synergism; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pyridines; Rhabdomyolysis; Ubiquinone; United States; United States Food and Drug Administration

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have effects that extend beyond cholesterol reduction. We used an angiotensin (Ang) II-dependent model to test the hypothesis that cerivastatin ameliorates cardiac injury.. We treated rats transgenic for human renin and angiotensinogen (dTGR) chronically from weeks 4 to 7 with cerivastatin (0.5 mg/kg by gavage). We used immunohistochemistry, electrophoretic mobility shift assays, and reverse transcription-polymerase chain reaction techniques. Compared with control dTGR, dTGR treated with cerivastatin had reduced mortality, blood pressure, cardiac hypertrophy, macrophage infiltration, and collagen I, laminin, and fibronectin deposition. Basic fibroblast growth factor mRNA and protein expression were markedly reduced, as was interleukin-6 expression. The transcription factors NF-kappaB and AP-1 were substantially less activated, although plasma cholesterol was not decreased.. These results suggest that statins ameliorate Ang II-induced hypertension, cardiac hypertrophy, fibrosis, and remodeling independently of cholesterol reduction. Although the clinical significance remains uncertain, the results suggest that statins interfere with Ang II-induced signaling and transcription factor activation, thereby ameliorating end-organ damage.

Topics: Angiotensin II; Angiotensinogen; Animals; Animals, Genetically Modified; Blood Pressure; Cardiovascular Diseases; CD4 Antigens; CD8 Antigens; Collagen; Fibroblast Growth Factor 2; Fibronectins; Gene Expression Regulation; Heart; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunohistochemistry; Interleukin-6; Male; Myocardium; NF-kappa B; Oligonucleotides; Protein Binding; Pyridines; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger; Survival Analysis; Survival Rate; Transcription Factor AP-1