Atorvastatin In Terms Research Articles

Comparison of the effect of atorvastatin and aspirin on C-reactive protein concentration in hemodialysis patients

Introduction: Chronic inflammation is one of the underlying causes of cardiovascular disease which is commonly seen in patients with chronic kidney disease (CKD) and especially in end-stage renal disease (ESRD), as well as the patients on stable dialysis. Hemodialysis patients suffer from high mortality due to cardiovascular diseases. Objectives: Therefore, the present study aimed to evaluate the effect of atorvastatin and aspirin on C-reactive protein (CRP) concentration in hemodialysis patients and compare the effect of these two drugs on CRP concentration in these patients. Patients and Methods: In this descriptive-analytical study, the dialysis patients who had been on dialysis for more than four months were selected through medical records (N=75). Serum CRP was checked and those who had positive CRP entered in the analysis (n=20). Ten patients had been used atorvastatin at a dose of 20 mg daily and the other 10 patients received aspirin at a dose of 80 mg daily for two months. Serum CRP concentration was measured in all patients at the end of these two months. Results: The mean age of the patients was 65.6 years and the mean number of years on dialysis was three years. In addition, 65% of patients were male and 35% were female. The only significant relationship was between the effect of atorvastatin and CRP concentration and the effect of aspirin on CRP concentration while no statistically significant relationship was found between the two groups of aspirin and atorvastatin in terms of serum CRP value after the intervention. Conclusion: The results indicated that the effect of aspirin and atorvastatin on CRP concentration was positive in hemodialysis patients and reduced the serum level of CRP, indicating the anti-inflammatory role of these two drugs in hemodialysis patients. It should be noted that drug preference was not determined in the present study.

Does Short Term Atorvastatin Treatment Improve Symptomatic Control in Patients with Mild to Moderate & Uncontrolled Asthma?

Introduction: Asthma is a chronic disease characterized by recurrent episodes of breathlessness and wheezing. Keeping in view the problems in asthma control and side effects of available medication, there is a need for alternative treatments with better efficacies and fewer side effects. Atorvastatin is a statin that blocks HMG CoA reductase enzyme found in the liver, inhibiting the synthesis of cholesterol. Blockade of this pathway also inhibits production of GTPases which are involved in airway inflammation, airway remodeling and contraction of smooth muscles of the bronchi. Aims & Objectives: To evaluate the symptomatic control in mild to moderate and uncontrolled asthma patients using standard treatment versus its combination with atorvastatin. Place and duration of study: This study was conducted in Pulmonology Department of Lahore General Hospital; Lahore over a 4-week duration from October 2018 till February 2019. Material & Methods: Patients of mild to moderate and uncontrolled asthma were enrolled in this study based on inclusion and exclusion criteria. Patients were divided into two groups by lottery method, Group 1 and Group 2, with 34 patients in each group. Group 1 was continued with standard therapy of asthma and the Group 2 was administered atorvastatin 40 mg, once daily in addition to standard therapy for 4 weeks. The control of asthma before and after treatment was assessed based on Global Initiative for asthma (GINA) guideline questionnaire score. SPSS (Statistical Package for Social Sciences) version 22 was used for analysis of data. P-Value < 0.05 was taken as significant. Results: Nonsignificant results were obtained when comparison between the groups was made based on GINA guidelines questionnaire score by Mann Whitney Utest Conclusion: It was concluded that atorvastatin has no role in symptomatic control in patients of mild to moderate and uncontrolled asthma.

Long Term Efficacy of Generic Atorvastatin by a University Hospital Database

Background: There is limited long term data of generic atorvastatin in terms of clinical efficacy and safety. This study aimed to evaluate the efficacy of generic atorvastatin in a 12-month period.
 Methods: This study was a retrospective cohort study. The inclusion criteria were adult patients who received the original atorvastatin for at least three months and then switched to the generic atorvastatin for 12 months. Lipid profiles and safety profiles were evaluated after 12 months of switching therapy.
 Results: During the study period, there were 297 patients met the study criteria. The mean (SD) age of the patients was 61.05 (11.51) years. Male sex accounted for 46.80% (139 patients). For lipid outcomes, only HDL-c was significantly increased by 2.05 mg/dL (p 0.001). Serum creatinine was increasing by 0.07 mg/dL, while eGFR was decreasing by 2.55 ml/min/1.73m2. Other laboratory outcomes were not significantly changed after one year including ALT, AST, and CK.
 Conclusions: Generic atorvastatin had comparable effect on LDL-c reduction compared with the original atorvastatin. Renal deterioration were found with increasing HDL-c level in this study population with generic atorvastation. Physicians should be aware of declining of renal function in long term use of generic atorvastatin.

To compare rosuvastatin with atorvastatin in terms of mean change in LDL-C in patient of diabetes mellitus.

Diabetes Mellitus is a very common metabolic disorder characterized by hyperglycemia and altered metabolism of lipids, proteins and carbohydrates due to absolute or relative insulin deficiency or insulin resistance. There is a close association between complications of Diabetes and Diabetic Dyslipidemias. The lowering of LDL levels with statins varies from 20 to 60% and greatest effects are seen with the most potent statins such as Atorvastatin, and Rosuvastatin in higher doses. Objectives: The objective of the study was; to compare Rosuvastatin with Atorvastatin in terms of mean change in LDL-C in patients of Diabetes Mellitus. Study Design: Randomized Control Trail. Setting: Department of Medicine DHQ Hospital, Faisalabad. Period: Six months from 01/10/2018 to 31/03/2019. Material & Methods: Results: A total of 160 cases (80 in each group) fulfilling the inclusive/exclusive criteria were enrolled to compare Rosuvastatin with Atorvastatin in terms of mean change in LDL-C in patients of Diabetes Mellitus. Mean LDL-C levels at baseline was recorded as159.61+1.22 in Group-A and 159.51+1.21 in Group-B, p value was calculated as 0.603 showing insignificant difference. Mean LDL-C after 6 weeks of treatment was recorded as129.11p+1.50 in Group-A and 129.89+2.23 in Group-B, p value was calculated as 0.01 showing significant difference. Mean change in LDL-C level after 6 weeks of treatment was recorded as 30.5+1.88 in Group-A and 29.63+2.57 in Group-B, p value was calculated as 0.01 showing a significant difference. The data was stratified for Age, Gender, Duration of Diabetes Mellitus and control of Diabetes Mellitus. Conclusion: This study proves superiority of Rosuvastain over Atorvastatin in reducing LDL-C level in type 2 DM Patients.

Imaging of Intracellular and Extracellular ROS Levels in Atherosclerotic Mouse Aortas Ex Vivo: Effects of Lipid Lowering by Diet or Atorvastatin

ObjectiveThe first objective was to investigate if intracellular and extracellular levels of reactive oxygen species (ROS) within the mouse aorta increase before or after diet-induced lesion formation. The second objective was to investigate if intracellular and extracellular ROS correlates to cell composition in atherosclerotic lesions. The third objective was to investigate if intracellular and extracellular ROS levels within established atherosclerotic lesions can be reduced by lipid lowering by diet or atorvastatin.Approach and ResultsTo address our objectives, we established a new imaging technique to visualize and quantify intracellular and extracellular ROS levels within intact mouse aortas ex vivo. Using this technique, we found that intracellular, but not extracellular, ROS levels increased prior to lesion formation in mouse aortas. Both intracellular and extracellular ROS levels were increased in advanced lesions. Intracellular ROS correlated with lesion content of macrophages. Extracellular ROS correlated with lesion content of smooth muscle cells. The high levels of ROS in advanced lesions were reduced by 5 days high dose atorvastatin treatment but not by lipid lowering by diet. Atorvastatin treatment did not affect lesion inflammation (aortic arch mRNA levels of CXCL 1, ICAM-1, MCP-1, TNF-α, VCAM, IL-6, and IL-1β) or cellular composition (smooth muscle cell, macrophage, and T-cell content).ConclusionsAortic levels of intracellular ROS increase prior to lesion formation and may be important in initiation of atherosclerosis. Our results suggest that within lesions, macrophages produce mainly intracellular ROS whereas smooth muscle cells produce extracellular ROS. Short term atorvastatin treatment, but not lipid lowering by diet, decreases ROS levels within established advanced lesions; this may help explain the lesion stabilizing and anti-inflammatory effects of long term statin treatment.

Abstract 488: Atorvastatin Inhibits Src/ROS-mediated Redox Sensitive And Pro-Inflammatory Actions of Aldosterone in Vascular Smooth Muscle Cells: Focus on Statins Pleiotropic Effects

Statins, described as cholesterol-lowering drugs, are now recognized to induce effects throught pleiotropic actions, including oxidative stress reduction and protein geranylgeranylation inhibition. Mechanisms whereby aldosterone associates with c-Src and related redox signaling molecules involve lipid rafts. This study aims to identify whether c-Src/NADPH oxidases (Nox) pathway is a statin-sensitive target independent of membrane cholesterol depletion mechanisms. In order to discriminate statin pleiotropic effects from its classic cholesterol synthesis inhibition, VSMCs from WKY were treated with 1 uM atorvastatin for 60 min or 72h prior 100 nM aldosterone stimulations respectively. Aldosterone-induced c-Src phosphorylation (% vehicle, 267 ± 35) was inhibited by long (150 ± 23 %) and short (114 ± 33 %) term atorvastatin treatment. To restore cholesterol synthesis, cells were incubated with its intermediate, mevalonate (100 μM). Mevalonate reload restored c-Src phosphorylation (287 ± 27 %) induced by aldosterone in atorvastatin long term-treated VSMCs. Geranylgeranyl-pyrophosphate (GGPP) was used to prevent protein geranylgeranylation inhibition. GGPP reposition recovered the effects of aldosterone on c-Src phosphorylation in both short (268 ± 22 %) and long (203 ± 35 %) term VSMCs treated with atorvastatin. Aldosterone-induced increase of Nox1, 2 and 4 expression and the associated ROS-generation (215 ± 38 %) were inhibited by long and short term atorvastatin incubation. Aldosterone-induced RAC1/2 and p47phox translocation (cytosol to membrane) was prevented by atorvastatin treatments. Aldosterone stimulation increased Nox1 and p47phox content in cholesterol-enriched fractions, an effect inhibited by atorvastatin short term treatment. Atorvastatin also prevented the increase of redox-signaling phosphorylation (ERK1/2, p38 and JNK) and pro-inflammatory markers (VCAM-1 expression, NFkB p65 phosphorylation) by aldosterone. We demonstrate that atorvastatin influences c-Src/Nox-mediated effects of aldosterone involving lipid rafts through classic and pleiotropic actions independent of cholesterol depletion. This study identifies a novel mechanism for statins in aldosterone-associated vascular injury.

Dose-dependent effects of short term atorvastatin treatment on arterial wall properties and on indices of left ventricular remodeling in ischemic heart failure

ObjectivesStatins, beyond their lipid lowering role, exert beneficial effect on endothelial function in patients with atherosclerosis. Aim of the present study was to examine the short term pleiotropic effects of different doses of atorvastatin treatment, on endothelial function, arterial stiffness and indices of left ventricular remodeling in heart failure (HF) patients. MethodsWe studied the effect of 4 weeks administration of atorvastatin in 22 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery and arterial stiffness by augmentation index (AIx). Serum levels of matrix metalloproteinase-9 (MMP-9) and intracellular adhesion molecule-1 (sICAM-1) were measured as biomarkers of left ventricular remodeling and endothelial function, respectively, while, b-type natriuretic peptide (BNP) was measured as a marker of left ventricular function. ResultsCompared to baseline, atorvastatin 40 mg/d significantly improved FMD values (3.18 ± 3.03% vs. 5.98 ± 2.49%, p = 0.001) and AIx values (25.98 ± 8.55% vs. 23.09 ± 8.87%, p = 0.046). In addition, compared to baseline measurements, treatment with atorvastatin 40 mg/d resulted in significantly decreased levels of serum logMMP-9 levels (2.47 ± 0.23 ng/ml vs. 2.39 ± 0.24 ng/ml, p = 0.04) and of logICAM-1 levels (2.46 ± 0.13 ng/ml vs. 2.37 ± 0.16 ng/ml, p < 0.001). No significant changes were found after treatment with atorvastatin 10 mg/d in the aforementioned parameters. ConclusionsShort term treatment with 40 mg/d of atorvastatin exerts beneficial impact on arterial wall properties and on indices of left ventricle remodeling in heart failure patients.

Cost-effectiveness analysis of rosuvastatin vs generic atorvastatin in Spain

Objective:The objective of this study was to carry out a long-term cost-effectiveness analysis of rosuvastatin compared with generic atorvastatin in the treatment of patients at high cardiovascular (CV) risk (≥5% Systematic COronary Risk Evaluation [SCORE]) and patients with prior cardiovascular disease (CVD) in Spain.Methods:The efficacy data from the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) study were used to simulate achievement of low-density lipoprotein cholesterol targets with different doses of rosuvastatin and generic atorvastatin for an initial period of 1 year. A Markov model was used to estimate the number of CV complications, quality-adjusted life years (QALYs), and healthcare costs (lipid-lowering treatment and CV events) for up to 20 years after initial treatment. The analysis was carried out from the perspective of the Spanish National Health System, with costs (in year 2010 euros) and effects being discounted at 3% per year.Results:Compared with generic atorvastatin, rosuvastatin was cost-effective (cost per QALY gained of less than €30,000) for the primary prevention of CV events in high-risk patients in most sub-groups analyzed. In patients with prior CVD, rosuvastatin was cost-effective in all sub-groups of men and most sub-groups of women. Key limitations of this study were the need to extrapolate data from a single trial to long-term modeled outcomes and the absence of other treatment options in the analysis.Conclusions:For the treatment of dyslipidemic patients with high CV risk, rosuvastatin is more effective than generic atorvastatin in terms of survival and quality-of-life adjusted survival, with incremental cost-effectiveness ratios within the range generally used in Spain, in most sub-populations defined by various combinations of CV risk factors.

Pitavastatin

Pitavastatin (Livazo®, Livalo®), an inhibitor of HMG-CoA reductase (statin), is indicated for the reduction of elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, in adult patients with primary hypercholesterolaemia and mixed dyslipidaemia, when response to diet and other non-pharmacological measures is inadequate. Pitavastatin has a favourable pharmacological profile following oral administration, including its long half-life (up to 12 hours), selective uptake into hepatocytes and minimal metabolism by cytochrome P450 (CYP) enzymes. This latter property decreases the likelihood of drug-drug interactions with agents that are metabolized by, inhibit or induce CYP enzymes. Pitavastatin improved the lipid profile (including LDL-C, TC and high-density lipoprotein cholesterol levels) in patients with hypercholesterolaemia and mixed dyslipidaemia, according to large, pivotal phase III studies of up to 60 weeks' duration. In these trials, pitavastatin for 12 weeks was noninferior to simvastatin and atorvastatin in terms of the improvement from baseline in LDL-C levels. In similarly designed trials, pitavastatin improved lipid profiles and was noninferior to simvastatin in patients with high cardiovascular risk and demonstrated significantly greater LDL-C reduction than pravastatin in elderly patients. Furthermore, in patients with type 2 diabetes mellitus, although noninferiority criteria for the comparison with atorvastatin were not met in terms of the improvement from baseline in LDL-C levels, pitavastatin was associated with some improvements in the lipid profile. Pitavastatin also demonstrated substantial lipid-modifying effects in exclusively Asian populations in well designed clinical trials. Pitavastatin was generally well tolerated in clinical trials of up to 60 weeks' duration, with a tolerability profile generally similar to that of atorvastatin and simvastatin. Therefore, pitavastatin appears to be an attractive alternative for the treatment of patients with primary hyperlipidaemia or mixed dyslipidaemia who have not responded adequately to diet and other non-pharmacological measures, and may present a useful treatment option in patients requiring polypharmacy, such as those at high risk of cardiovascular disease. Further studies evaluating the effects of pitavastatin on clinical endpoints, such as cardiovascular morbidity and mortality, are required to confirm the longer-term benefits of pitavastatin.

Possible mechanisms of interaction between statins and vitamin D

Myalgia, the most common statin-related complaint, may affect 10–15% of patients on statins1 and affect patient compliance. There have been several reports regarding the relationship between vitamin D deficiencies and statin-induced myalgia.2–6 In addition, vitamin D levels have been reported to affect the lipid lowering actions of some statins.8,9 The mechanism of these interactions is poorly understood and is believed to contradict the expected action of vitamin D on statin metabolism.7 In a published review,7 authors speculate that vitamin D, by activating CYP3A4, should decrease atorvastatin levels and the efficacy of atorvastatin in reducing total and LDL cholesterol, but the opposite has been observed.8 In this article, we have tried to connect the missing links between the statin metabolism and the actions of vitamin D in inducing statin metabolism. We researched the chemistry and metabolism of the statins especially in terms of the role of Cytochrome P-450 (CYP). Since not all the statins are metabolized similarly, the effect of vitamin D on their metabolism is not universal. ### Vitamin D levels and statin effectiveness Some research data suggest that there is a relationship between vitamin D levels and statin effectiveness. One research has suggested that adequate vitamin D levels >30 nmol/l may be required for atorvastatin to reduce lipid levels8 because 63 vitamin D-deficient patients did not respond to low- or high dose of atorvastatin in terms of total cholesterol or LDL at 12 months while patients with insufficient and normal levels of vitamin D showed expected reduction in cholesterol. In one additional study,9 supplemental vitamin D (800 IU/day) enhanced the effect of atorvastatin therapy on total and LDL cholesterol ( P < 0.005). ### Vitamin D deficiency and statin myopathy There is also evidence for the relationship of vitamin D deficiency to statin myopathy.2–6 One study3 reported resolution of myalgia (92%) …

Short term statin treatment in idiopathic dilated cardiomyopathy

Abstract Background Statins may provide additional benefits in patients with cardiac failure due to their pleiotropic effects besides their cholesterol-lowering actions. In this study, we aimed to evaluate the impact of 12-week 40 mg atorvastatin therapy on the inflammatory markers, endothelium dependent vasodilatation and the ventricular performance markers in patients with heart failure (HF). Methods and results Thirty chronic symptomatic heart failure patients, all with idiopathic dilated cardiomyopathy (DCM) were included to this open label and prospective study. Thirty patients were subdivided into two groups: group I – 15 patients who were given 40 mg of atorvastatin and group II – 15 patients who were given a placebo. After a 12-week treatment with atorvastatin 40 mg/day; clinical functional capacity, echocardiographic indices of cardiac performance and inflammatory markers were evaluated. After the treatment, even though the left ventricular ejection fraction (LV EF) did not improve significantly in the group receiving statins (29.2 ± 6.18 to 29.73 ± 6.27 in the statin group and 28.13 ± 5.81 to 27.93 ± 5.56 in the control group), both the 6 min walk test and Minnesota living with heart failure questionnaire improved significantly ( p = 0.000 and 0.022, respectively). The flow mediated dilatation in the brachial arteries also showed improvement in the statin receiving group (8.9–13.8 in the statin group p = 0.0001, and 9.5–10.2 in the control group p = 0.055). In addition, the statin receiving group showed significantly lower levels of highly sensitive C-reactive protein (hs-CRP) levels at follow up (4.6–1.93 in statin group p = 0.005, and 7.2–4.97 in the control group p = 0.176). Conclusion Short term atorvastatin treatment improved functional capacity and the clinical symptoms in HF patients with idiopathic dilated cardiomyopathy. This positive effect of atorvastatin might be secondary to inflammatory modulation and improvement of endothelial function. Statins in HF deserve special attention by means of further large-scale trials.

Comparison of efficacy and adverse effect profile of high dose versus standard dose atorvastatin in acute ST elevation myocardial infarction patients

ObjectiveTo compare the efficacy and adverse effects of high and standard dose atorvastatin in ST elevation myocardial infarction (STEMI) patients.DesignA prospective, single-centre, randomised, double blind study.SettingA tertiary care centre in...

Therapy and clinical trials

In the VYTAL (Vytorin versus Atorvastatin in Patients with Type 2 Diabetes Mellitus and Hypercholesterolemia) study, Goldberg et al. [2 •• ] compared the usual starting doses of ezetimibe/simvastatin (10/20 mg/day) with those of atorvastatin (10 or 20 mg/day), and the next highest doses of these agents (ezetimibe/simvastatin 10/40 mg/day versus atorvastatin 40 mg/day) over 6 weeks. In their double-blind multicenter study, the investigators demonstrated a significantly greater mean reduction in LDL-cholesterol levels with ezetimibe/simvastatin 10/20 mg/day (53.6%) than with atorvastatin 10 mg/day (38.3%) or 20 mg/day (44.6%). Also, they found that ezetimibe/simvastatin 10/40 mg/day yielded a greater reduction in LDLcholesterol (57.6%) than did atorvastatin 40 mg/day (50.9%). The combination therapy at both doses was superior to atorvastatin with respect to the increase in HDL-cholesterol levels and decrease in non-HDL-cholesterol levels. With regard to plasma triglycerides and highsensitivity CRP levels, however, the reduction in levels was significant only for the 10/20 mg/ day dose of ezetimibe/simvastatin. Although only the 10/20 mg dose of ezetimibe/simvastatin was superior to atorvastatin in terms of reducing LDL-cholesterol to below 100 mg/dl,

Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL

Background HMG-CoA-reductase-inhibitors (statins) exhibit pleiotropic beneficial effects on the vascular system including induction of endothelial nitric oxide synthase (eNOS) expression which is critical for vasodilation. Recent studies suggest a beneficial effect of statins on cerebral vasoreactivity in patients with cerebral small vessel disease (SVD). CADASIL is a monogenic form of SVD caused by mutations in the Notch3 gene. Treatment options are limited and little is known about the therapeutic role of statins in CADASIL. Methods Twenty-four CADASIL subjects were treated with atorvastatin for 8 weeks. Treatment was started with 40 mg, followed by a dosage increase to 80 mg after 4 weeks. Transcranial Doppler sonography measuring mean flow velocity (MFV) in the middle cerebral artery was performed at baseline and the end of the treatment period. Vasoreactivity was assessed by hypercapnia and intravenous application of l-Arginine, which is the substrate for eNOS. Results There was no significant treatment effect on MFV ( p = 0.5) or cerebral vasoreactivity as assessed by hypercapnia ( p = 0.5) and intravenous l-Arginine ( p = 0.4) in the overall cohort. However, an inverse correlation was found between vasoreactivity at baseline and changes of both CO 2 and l-Arginine-induced vasomotor response (both p < 0.05). Conclusions Short term treatment with atorvastatin resulted in no significant improvement of hemodynamic parameters in the overall cohort of CADASIL subjects.

W07.184 Serum activity of proinflammatory cytokines in patients with unstable angina or non persistent ST elevation myocardial infarction. Effects of short term atorvastatin administration

W07.184 Serum activity of proinflammatory cytokines in patients with unstable angina or non persistent ST elevation myocardial infarction. Effects of short term atorvastatin administration

W07.184 Serum activity of proinflammatory cytokines in patients with unstable angina or non persistent ST elevation myocardial infarction. Effects of short term atorvastatin administration

W07.184 Serum activity of proinflammatory cytokines in patients with unstable angina or non persistent ST elevation myocardial infarction. Effects of short term atorvastatin administration

Are Antiplatelet Effects of Clopidogrel Inhibited by Atorvastatin?

With respect to antiplatelet therapy, randomized trials and their meta-analyses 1 indicate benefits of clopidogrel either as an alternative 2 or an adjunct 3 to aspirin in some high-risk patients. Regarding the metabolic pathways of clopidogrel, the active thiol metabolite binds rapidly and irreversibly to platelet adenosine diphosphate (ADP) receptors, thus inhibiting platelet aggregation. 4 Clopidogrel, a thienopyridine, is a platelet ADP-receptor blocker that is known to be beneficial during and after coronary stenting.2–5 Clopidogrel is extensively metabolized by the liver. The main circulating metabolite is the carboxylic acid derivative, which has no effect on platelet aggregation. The active metabolite, a thiol derivative, is formed by oxidation of clopidogrel to 2-oxo-clopidogrel and subsequent hydrolysis. Results of in vitro studies in human liver microsomes and recombinant cytochromes P450 have shown that several cytochromes are involved in the oxidative metabolism of clopidogrel.6 In randomized trials of secondary and primary prevention of cardiovascular disease and their meta-analyses, 7 statins reduce risks of myocardial infarction, stroke, and cardiovascular death. Recently, in a randomized trial in patients undergoing percutaneous coronary intervention, 8 statins have been shown to reduce the incidence of major adverse coronary events, especially among the subgroups of diabetics and those with multivessel disease. In these high-risk patients, the National Cholesterol Education Program III guidelines recommend statin therapy to achieve low-density lipoprotein (LDL) goals of less than 100 mg/dL. 9 Of the 5 marketed statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin), four (atorvastatin, fluvastatin, lovastatin, and simvastatin) are also metabolized by the cytochrome P450 pathway. 10 Thus, in patients receiving coronary stents, both clopidogrel and statin therapy are likely to contribute to beneficial effects on subsequent cardiovascular disease. A recent report has raised the possibility that the ability of clopidogrel to affect platelets is inhibited by atorvastatin. 11 We have a number of concerns about the validity of these findings and therefore believe the totality of evidence to be far from complete and not consistent. In that study, the sample size was small (n44), patient selection was poorly defined, no control for the presence of medications affecting CYP 450 3A4 pathway was performed before initiation, and the data were retrospective and non-randomized. Using a single method to assess platelet function was also unconventional. Furthermore, data from the larger retrospective Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial compared platelet inhibition with clopidogrel in 100 patients undergoing coronary intervention who also received statins. 12 In PRONTO, there was no evidence of any specific deleterious interaction between clopidogrel and atorvastatin in terms of platelet activity. The analysis showed that only 4 of 25 patients in the atorvastatin treated group did not exhibit sustained platelet inhibition on days 2 and 5 after treatment with clopidogrel and aspirin. A similar pattern was observed in 2 of 9 patients treated with fluvastatin and 1 of 6 patients treated with pravastatin, neither of which is metabolized by the cytochrome P450 3A4 pathway. Finally, of perhaps even greater relevance to this hypothesis, a similar pattern was observed in 12 of 75 patients who did not receive any statin. In total, about 20% of patients did not achieve profound platelet inhibition with clopidogrel, but this seemed unrelated to treatment with any statins. It is tempting to speculate that in certain patients, the burden of platelet activation is so excessive that usual treatment regimens are not sufficient to achieve even moderate platelet inhibition. Retrospective data from the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) and Clopidogrel Unstable angina to prevent Recurrent Events (CURE) trials among subgroups of patients concurrently administered clopidogrel and statins indicated no clinically significant adverse interactions. Further data, especially from prospective studies, are necessary to test the hypothesis of potential interactions between clopidogrel and statins. One such study, INTERACTIONs of atorvastatin and clopidogrel therapy (INTERACT), has been designed to address this issue by serial measurements of various platelet characteristics by conventional as well as whole blood aggregometry, by point of care tests with 2 rapid analyzers, and by assessment of 14 receptors on the platelet surface by whole blood flow cytometry.

A new statin, rosuvastatin, produces significant improvements in serum lipids and lipid ratios in patients with hypercholesterolaemia

Background: Previous health economic studies have demonstrated the cost-effectiveness of simvastatin in the treatment of coronary heart disease (CHD) based on clinical results of the Scandinavian Simvastatin Survival Study. A prior analysis evaluated the “cost of getting to goal,” but ignored all costs after titration. However, when evaluating the cost-effectiveness of long-term therapies, it is important to consider the maintenance costs as well.Objective: The purpose of this study was to evaluate the maintenance costs of treatment with simvastatin versus that of treatment with another more recently available statin, atorvastatin, in a European context.Methods: We assessed the long-term maintenance cost of simvastatin versus atorvastatin in terms of the cost of reducing low-density lipoprotein cholesterol (LDL-C) levels to the recommended goals based on a previously published clinical trial in patients with CHD. The analysis focused on the patients in the original clinical trial who were randomized to treatment with simvastatin or atorvastatin. Patients began therapy with 10 mg of simvastatin or atorvastatin; the dose of study drug was titrated every 12 weeks up to 40 mg simvastatin or 80 mg atorvastatin, with the addition of up to 8 g/d of cholestyramine until a modified European Atherosclerosis Society LDL-C goal (≤2.84 mmol/L) was reached. As there was no significant difference between the 2 groups in resource utilization for adverse events, only drug costs were included. The calculated average annual maintenance cost was based on the distribution of the final daily dosing regimens and the public drug prices for each regimen. Individual country analyses were conducted using each local currency.Results: There was no significant difference between groups in the percentage of patients reaching their LDL-C goal over the study period (80% for simvastatin-treated patients vs 89% for atorvastatin-treated patients, P = 0.135). However, the cost of maintaining a similar percentage of patients at their appropriate LDL-C levels was significantly lower in the simvastatin group compared with the atorvastatin group in 13 of the 17 countries assessed. In the remaining 4 countries, there was a cost advantage for simvastatin, but it did not reach statistical significance.Conclusions: Across Europe there was a significant reduction in the cost of maintaining patients at their appropriate LDL-C levels with simvastatin versus atorvastatin. The results of this analysis, along with the proven clinical benefits of simvastatin, support the use of this drug as the treatment of choice in the secondary prevention of CHD.

Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease

Background: Previous health economic studies have demonstrated the cost-effectiveness of simvastatin in the treatment of coronary heart disease (CHD) based on clinical results of the Scandinavian Simvastatin Survival Study. A prior analysis evaluated the “cost of getting to goal,” but ignored all costs after titration. However, when evaluating the cost-effectiveness of long-term therapies, it is important to consider the maintenance costs as well. Objective: The purpose of this study was to evaluate the maintenance costs of treatment with simvastatin versus that of treatment with another more recently available statin, atorvastatin, in a European context. Methods: We assessed the long-term maintenance cost of simvastatin versus atorvastatin in terms of the cost of reducing low-density lipoprotein cholesterol (LDL-C) levels to the recommended goals based on a previously published clinical trial in patients with CHD. The analysis focused on the patients in the original clinical trial who were randomized to treatment with simvastatin or atorvastatin. Patients began therapy with 10 mg of simvastatin or atorvastatin; the dose of study drug was titrated every 12 weeks up to 40 mg simvastatin or 80 mg atorvastatin, with the addition of up to 8 g/d of cholestyramine until a modified European Atherosclerosis Society LDL-C goal (≤2.84 mmol/L) was reached. As there was no significant difference between the 2 groups in resource utilization for adverse events, only drug costs were included. The calculated average annual maintenance cost was based on the distribution of the final daily dosing regimens and the public drug prices for each regimen. Individual country analyses were conducted using each local currency. Results: There was no significant difference between groups in the percentage of patients reaching their LDL-C goal over the study period (80% for simvastatin-treated patients vs 89% for atorvastatin-treated patients, P = 0.135). However, the cost of maintaining a similar percentage of patients at their appropriate LDL-C levels was significantly lower in the simvastatin group compared with the atorvastatin group in 13 of the 17 countries assessed. In the remaining 4 countries, there was a cost advantage for simvastatin, but it did not reach statistical significance. Conclusions: Across Europe there was a significant reduction in the cost of maintaining patients at their appropriate LDL-C levels with simvastatin versus atorvastatin. The results of this analysis, along with the proven clinical benefits of simvastatin, support the use of this drug as the treatment of choice in the secondary prevention of CHD.