High-dose Atorvastatin Group Research Articles

Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes.

BackgroundHigh-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D.Materials and MethodsT2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks.ResultsMean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was −0.1% and +0.1% (p=0.03) at 6 weeks, and −0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks.ConclusionSwitching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Effects of High Dose of Atorvastatin for Preventing Periprocedural Ischemic Brain Damage in Patients Undergoing Carotid Artery Stenting (PICAS) in China: A Randomized Controlled Clinical Trial.

Background: Research conducted in Western countries has suggested that high-dose statin therapy can lead to the regression of carotid atherosclerotic plaques and can reduce periprocedural ischemic complication rates in individuals undergoing carotid artery stenting (CAS). However, whether this same therapeutic approach is of value in patients of Chinese ethnicity is not as well-established.Methods: This is a single-center, prospective, parallel-controlled, intervention-based efficacy study that will enroll a total of 130 Chinese patients with cervical carotid stenosis who are scheduled to undergo CAS. These patients will be randomly divided into a routine treatment group and a high-dose atorvastatin group. Individuals in the routine treatment group will be administered standard of care 20 mg/day atorvastatin treatment. Individuals in the high-dose atorvastatin group will be administered 80 mg/day atorvastatin for 3 days prior to and following CAS. The primary outcome of this study will be the cumulative incidence of new cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging (DW-MRI) within 5 days following CAS, and of transient ischemic attacks (TIAs) or ischemic stroke within 30 days after CAS.Discussion: This study is the first to assess whether high-dose atorvastatin treatment is capable of reducing the incidence of perioperative cerebral ischemic injury in patients of Chinese ethnicity undergoing CAS. These results will offer evidence regarding which statin treatment regimens are more appropriate when treating Chinese patients undergoing CAS in an effort to minimize their risk of any perioperative cerebral ischemic injury.Trial Registration: ClinicalTrials.gov NCT03079115; registered March 14, 2017.

The Role of Wnt/beta-Catenin Signal Pathway in the Pathogenesis of Nonalcoholic Fatty Liver Disease and the Effect of Atorvastatin Intervention

The purpose of this study was to analyze the pathogenesis of nonalcoholic fatty liver disease in rats and study the efficacy of atorvastatin intervention. One hundred Sprague Dawley rats were selected as test system. These rats were randomly divided into 5 groups, the control group, the nonalcoholic fatty liver disease group, high-dose atorvastatin group, medium-dose atorvastatin group and low-dose atorvastatin group, each containing 20 animals. An equal dose of sodium carboxymethylcellulose was applied to the model group and the control group; while atorvastatin perfusion was given to the other 3 groups. The levels of serum aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein and malondialdehyde were compared among the groups. The serum levels of aspartate aminotransferase, alanine aminotransferase, triacylglycerol and total cholesterol of the high-fat diet model group were significantly higher; moreover, the expression levels of MMP2, MMP9, Wnt1, Wnt4, host-catenin were significantly elevated. Treatment with atorvastatin could effectively ameliorate this abnormal condition but at high doses. Atorvastatin appears to inhibit the Wnt/β-catenin signal pathway and achieve good curative effect against nonalcoholic fatty liver disease.

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System.

To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI). Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL. TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

High Loading Dose of Atorvastatin for the Prevention of Serum Creatinine and Cystatin C-Based Contrast-Induced Nephropathy Following Percutaneous Coronary Intervention.

The aim of this study is to assess the efficacy of high-dose atorvastatin on the prevention of contrast-induced nephropathy (CIN) in patients with acute coronary syndrome (ACS) undergoing percutaneous intervention and observe the incidence of cystatin C (CyC)-based CIN. A total of 496 patients with ACS were randomly assigned to either the control group (247 patients receiving conventional dose atorvastatin 10 mg daily from 1 day before to 3 days after contrast administration) or the high-dose atorvastatin group (249 patients receiving atorvastatin 40 mg daily for the same perioperative period). The baseline characteristics of the 2 groups were similar. The primary end point of serum creatinine (SCr)-based CIN occurred in 31 patients in the control group and 16 patients in the high-dose atorvastatin group (12.6% vs 6.4%; P = .02). Cystatin C-based CIN developed in 90 patients in the control group and 46 patients in the high-dose atorvastatin group (36.4% vs 18.5%; P < .001). A multivariable analysis revealed that high-dose atorvastatin was independently associated with a decreased risk of CIN. Our study demonstrated that prophylactic treatment with high-dose atorvastatin reduced the risk of both SCr and CyC-based CIN and suggested that CyC was a more reliable marker for early diagnosis of CIN compared with SCr.

Clinical effect of preoperative high-dose atorvastatin against no-reflow after PCI.

The aim of the present study was to evaluate the use of preoperative high-dose atorvastatin to prevent the no-reflow phenomenon after percutaneous coronary intervention (PCI). A total of 138 patients with ST-segment elevation myocardial infarction, admitted from March 2014 to January 2015, were enrolled and randomly divided into 3 groups of 46 individuals each. The groups included a control group in which patients were not treated with atorvastatin before PCI; a conventional-dose atorvastatin treatment group in which patients received a single dose of 20 mg at bedtime one day prior to PCI; and a high-dose atorvastatin treatment group in which patients were treated with 40 mg divided in two doses the day before PCI. The treatment effects were assessed by re-examining the echocardiography, high-sensitivity C-reactive protein and brain natriuretic peptide (BNP) levels after the PCI. The follow-up examinations included determinations of ultrasound imaging indicators and the contact with patients was maintained for a whole year. The CTFC (frame), pro-BNP, CK-MB peak and WMSI levels of the patients in the high-dose treatment group were significantly lower than those in the conventional dose or the control group. Trombolysis in myocardial infarction ≤2 and myocardial blush grade ≤1 levels were significantly lower than those in the conventional dose group (P=0.01) or those in the control group (P=0.01), although the echocardiographic indicators of the three groups were not significantly different (P<0.05). Nevertheless, it was found that there were significantly fewer adverse cardiovascular events in the high-dose group (P<0.05 in both cases). During the follow-up period, thromboembolism and restenosis were most infrequent in the high-dose atorvastatin group. Based on our findings the oral administration of high-dose atorvastatin before bedtime, one day before the procedure, can effectively prevent no-reflow cases, reduce adverse events and improve the long-term prognosis for acute coronary syndrome patients after PCI.

Atorvastatin protects endothelium by decreasing asymmetric dimethylarginine in dyslipidemia rats.

BackgroundAsymmetric Dimethylarginine (ADMA) is an inhibitor of endogenous nitric oxide synthase, which is the key synthase for nitric oxide (NO) production. Whether statins could protect endothelium by reducing ADMA concentration is unclear, and whether this effect is associated with the dose of statins usage is also needed further studied.MethodsDyslipidemia rat model was produced by giving high-fat and high-cholesterol diet for 8 weeks. Thereafter, low-dose (5 mg/kg body weight/day) and high-dose (20 mg/kg body weight/day) atorvastatin were orally prescribed for 4 weeks. Parameters of interest including lipid profiles, inflammatory and oxidative markers, NO production and plasma levels of ADMA and ADMA concentration of myocardium were evaluated. Liver enzymes and creatinine kinase (CK) were also detected for safety concern.ResultsAt baseline, all parameters were comparable between the sham and the dyslipidemia groups. At 8 weeks of dyslipidemia establishment, as compared to the sham group, body weight and lipid profiles were significantly elevated, and plasma levels of C-reactive protein (CRP), malondialdehyde (MDA) and ADMA were concomitantly increased in accompanying with NO reduction in the dyslipidemia groups. With 4 weeks of atorvastatin therapy, as compared to the control group, lipid disorders and NO production were improved, and plasma levels of CRP, MDA and ADMA were significantly decreased in the high-dose atorvastatin group. ADMA concentration of cardiac tissues was also significantly reduced in the high-dose atorvastatin group. Notably, there was a trend to similar effects which did not reach statistical significance in the low-dose atorvastatin group when compared to the control group. Liver enzyme and CK were comparable after 4 weeks of atorvastatin therapy between groups.ConclusionIn rats with dyslipidemia, atorvastatin therapy could reduce plasma level of ADMA and ADMA concentration in cardiac tissues, and these effects are associated with the dose of atorvastatin therapy.

Effects of high versus low-dose atorvastatin on high sensitive C-reactive protein in acute coronary syndrome.

Background:Cardiovascular disease is the leading cause of mortality. The previous findings which suggest the reduction in C-reactive protein (CRP) levels by statin encouraged us to conduct the present study in which we tested the effects of atorvastatin, on levels of hs-CRP in a prospective randomised clinical trial study on patients with acute coronary syndrome.Materials and Methods:Present prospective randomised clinical trial study conducted on 180 patients who had developed coronary artery disease and presented in emergency departments of Educational-Medical centers of Tabriz University of Medical Sciences. The patients were divided randomly into two groups and then two therapeutic protocols were given to them. One group medicated by high-dose atorvastatin (40 mg) and the other group received low-dose atorvastatin (20 mg). All variables were collected by questionnaires and were analyzed.Results:There were 180 patients consisted of 34 females and 56 males in low-dose atorvastatin group (L-DA group), and 30 females and 60 males in high-dose atorvastatin group (H-DA group) (P = 0.533). In this study atorvastatin in high doses decreased hs-CRP levels about 40% and in low doses it only caused decrease of 13.3%, and significant correlation was observed between two groups (Paired Sample T-test) (P = 0.001). Also atorvastatin in high doses decreased LDL levels about 23% and in low doses it only decreased 10%, and significant correlation was observed between two groups (Paired Sample T-test) (P = 0.001). Atorvastatin in high doses decreased HDL levels about 9% and in low doses it only decreased 6%, and again significant correlation was observed between two groups (P = 0.009).Conclusion:The present study confirms the novel observation that atorvastatin therapy results in a significant reduction in hs-CRP levels.

Study on anti-atherosclerotic effect of suxiao jiuxin pill and its mechanism.

Suxiao Jiuxin Pill is composed of Ligusticum wallichii, Borneolum Syntheticum and other drugs; it has qi promoting and blood circulation activating, meridian dredging and pain relieving efficacies. The objective of this paper is to study the effect of Suxiao Jiuxin Pill (quick-acting heart reliever), in atherosclerosis (AS) rat model and explore the mechanism for its prevention and treatment of AS. AS rat model was established by high cholesterol diet and single intra-peritoneal injection of increased dose of vitamin D3. Compared with the model group, Suxiao Jiuxin Pill medium-and high-dose groups and atorvastatin group can effectively regulate lipid metabolism. We conclude that Suxiao Jiuxin Pill has a good hypo-lipidemic effect, and can inhibit the occurrence and development of AS.

EFFECT OF ATORVASTATIN ON SCAVENGER RECEPTOR CLASS B TYPE I EXPRESSION IN THE LIVER OF GOLDEN HAMSTER WITH DIABETES

ObjectivesScavenger receptor class B type I (SR-BI) had been already proved in molecular level as the sole HDL receptor on cellular membrane. SR-BI plays an important role in reverse cholesterol...

THE EFFECTS OF 80 MG LOADING DOSE ATORVASTATIN PRETREATMENT ON MYOCARDIAL PROTECTION DURING PERCUTANEOUS CORONARY INTERVENTION IN ELDERLY PATIENTS WITH NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME

ObjectivesThis study was designed to evaluate the peri-procedural myocardial injury and safety profile of atorvastatin in patients over 70 years old with non-ST segment elevation acute coronary syndromes (NSTEACS).MethodsA total...

Reducing Residual Risk in Secondary Prevention of Cardiovascular Disease

Prevention of cardiovascular disease (CVD) spans the human lifespan, including primordial, primary, and secondary prevention efforts. Extensive evidence from epidemiological, genetic, and animal studies confirms the central importance of elevated low-density lipoprotein (LDL) cholesterol (LDL-C) in atherosclerotic CVD events.1 The Cholesterol Treatment Trialists Collaboration provides per-person documentation from large-scale randomized clinical trials of the striking reduction in CVD events per 1 mmol (38.8 mg/dL) of LDL-C lowering with statins over a wide range of baseline LDL-C values.2,3 It is worth recalling that the major statin trials were not designed to determine the effectiveness of titration to LDL-C or even to non–high-density lipoprotein cholesterol goals by statins but were fixed-dose comparisons of various statins against placebo and then, more recently, large-dose statin therapy versus moderate-dose statin therapy. What is not so clear is whether we can intervene to reduce so-called residual risk further in secondary prevention patients optimally treated with statin therapy. A promising short list of proposed potential targets other than LDL includes efforts to promote smoking cessation and therapies to improve the prothrombotic and inflammatory state of the metabolic syndrome and to control elevated blood pressure.4 Article see p 1979 The article by Mora et al5 in this issue of Circulation is helpful in shedding light on this unresolved but important clinical problem. The investigators used data from a large-scale clinical trial of secondary prevention patients called Treating to New Targets (TNT). They evaluated risk factors for recurrent CVD events in those treated with intensive statin therapy (atorvastatin 80 mg/d) to address the challenges inherent in further risk reduction for those who had major cardiovascular events despite high-dose (atorvastatin 80 mg/d) statin therapy. The trial design of TNT included enrollment of participants with chronic coronary artery …

Efficacy of short-term high-dose atorvastatin for prevention of contrast-induced nephropathy in patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention

BackgroundContrast-induced nephropathy (CIN) is a commonly occurring complication associated with the use of contrast media in radiological studies. It impairs clinical outcome in patients undergoing angiographic procedures.ObjectivesThe aim of this...

Effect of niacin on vascular endothelial cells in rats with atherosclerosis

Objective To explore the effect of niacin on vascular endothelial cells in rats with atherosclerosis (AS) and the mechanism of action of niacin for AS. Methods Rats with AS were divided into5 groups: groups with niacin at high (1500 mg/kg-1/d-1), medium (150 mg), and low dose (15 mg), group with high-fat diets, group with atorvastatin (5 mg/kg-1/d-1). Rats in the blank control group received normal diets.6 weeks after treatment, blood levels of NO, NOS, ET-1, and PAI-1 were detected in all the rats. The area of fibrous plaques and the media proliferation of the abdominal aorta were observed. Results In 3 niacin groups, NOS activity and NO level increased while levels of ET and PAI-1 decreased, and there was no significant difference between the three groups (P>0.05). The rate of media proliferation of the abdominal aorta decreased in niacin groups in a dose-dependent manner and it did not differ significantly between high-dose niacin group and atorvastatin group (P>0.05). Conclusions Niacin can improve the function of vascular endothelial cells and play a role in resisting atherosclerosis progress. Key words: Niacin; Atherosclerosis; Vascular endothelial cell; Nitric oxide; Endothelium; Plas-minogen activator inhibitor type 1

Beyond LDL-Cholesterol: The Role of Low HDL-Cholesterol and Elevated TG in Residual Cardiovascular Risk Remaining After Statin Therapy

One of the most effective classes of medications for preventing cardiovascular events is 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, more commonly known as statins. Statin therapy has been shown to decrease cardiovascular morbidity and mortality rates in virtually every patient population studied and will likely continue to be a mainstay of cardiovascular risk prevention for years to come. However, close examination of statin clinical trial data reveals that, even though this class of drugs has been highly effective, an unacceptably large number of patients on statins still experience cardiovascular events. For example, in the Scandinavian Simvastatin Survival Study (4S) trial, which studied patients with very high levels of low-density lipoprotein cholesterol (LDL-C and known coronary heart disease (CHD), a significant risk reduction was observed with statin treatment. A greater percentage of patients on placebo (28%) experienced a major cardiovascular event than did patients on statin therapy (19%), and the relative risk of a major cardiovascular event in the statin-treated patients was 0.66.27 On the other hand, those results from 4S also indicate that, over the 5 years of the study, almost 20% of statin-treated patients still had a cardiovascular event. In several major statin trials, significant residual cardiovascular risk remained even after significant reductions in LDL-C had been achieved.27-32 Thus, despite the decrease in cardiovascular events due to statin treatment, two-thirds of the adverse cardiovascular events still occurred, which indicates that both patient lifestyle changes and new pharmacological strategies are necessary to address cardiovascular disease.33 Additional trials have included high-risk patients with CHD or diabetes who were treated with intensive LDL-lowering statin therapy. In 3 of these trials, as shown in Figure 1, lowering LDL-C to approximately 100 mg per dL was compared with more intensive LDL-C lowering to approximately 70 mg per dL to investigate cardiovascular event reduction even in high-risk patient populations.14-16,34 In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) study, 4,162 patients with acute coronary syndrome (ACS) were treated with either pravastatin 40 mg or atorvastatin 80 mg. Treatment with pravastatin reduced LDL-C to 95 mg per dL, whereas treatment with high-dose atorvastatin reduced LDL-C to 62 mg per dL.14 Clinical events were reduced in the high-dose atorvastatin group versus the pravastatin group; however, over the course of the 2-year trial, 22.4% of the individuals treated with intensive statin therapy (atorvastatin 80 mg) still suffered a major cardiovascular event.14 Similar results have been observed in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study and the Treating to New Targets (TNT) study. After 4.8 years in the IDEAL study, 12.0% of patients experienced a major cardio vascular event even after intensive LDL-C lowering with 80 mg per day of atorvastatin.16 In the TNT trial, after 4.9 years of follow-up, 8.7% of patients receiving 80 mg per day of atorvastatin still suffered a major cardiovascular event.15 Thus, significant residual cardiovascular risk remains in patients even after intensive statin therapy that achieves LDL-C goals < 100 mg per dL.14-16,34 Patients with diabetes, another high-risk population, show significant cardiovascular risk reduction when treated with statins. A meta-analysis of 14 statin trials by the Cholesterol Treatment Trialists’ Collaborators examined data of major vascular events in patients with diabetes.2 A reduction in LDL-C in individuals with a prior history of CHD and either with or without diabetes was associated with a significant reduction in cardiovascular events. There was a 9% proportional reduction in all-cause mortality per 1 mmol per L (39 mg per dL) reduction in LDL-C in individuals with diabetes (P = 0.02) and a 13% reduction in those without diabetes (P < 0.001). Moreover, there was a significant 21% reduction in major vascular events per 1 mmol per L (39 mg per dL) reduction in LDL-C in people with diabetes (P < 0.001) and those without diabetes (P < 0.001).2 Nonetheless, in patients with diabetes treated with statin therapy, the cardiovascular event rate (i.e., residual cardiovascular risk) remained unacceptably high, and was even higher than the cardiovascular event rate of those patients without diabetes who received placebo.2 It is clear, then, that residual cardiovascular risk remains in all patients treated with statins, and that the residual cardiovascular risk is particularly high in patients with diabetes treated with statins.

CORONA, Statins, and Heart Failure: Who Lost the Crown?

Several small, nonrandomized studies suggested that statin use is associated with improved outcomes in CHF irrespective of aetiology (ischemic or not) or baseline cholesterol levels. Recently, 2 large cohort studies provided more convincing evidence that statins can improve the outcome in this population. In 24,598 patients with CHF who were eligible for treatment with statins, incident statin use was associated with a 21% and 24% reduction in hospitalization for CHF and total mortality, respectively. In an even larger study of 54,960 patients older than 65 y who were hospitalized due to CHF, statin therapy at discharge was associated with a 20% and 18% reduction in 1and 3-y mortality, respectively. Similar findings were reported in small, subgroup analyses of RCT. The Treating to New Targets (TNT) trial randomized 10,001 patients with stable coronary heart disease (CHD) to receive either 10 mg or 80 mg atorvastatin. In the CHF TNT subgroup analysis, rates of the predefined secondary endpoint of CHF hospitalization were significantly lower in the high-dose atorvastatin group (26% lower, P = .0116). Among the TNT population, 7.8% had a prior diagnosis of CHF; their mean age was 64 y. In these patients, high-dose atorvastatin reduced CHF hospitalization rates by 41% (P = .008). In patients without a history of CHF, hospitalization rates for CHF were similar in the Observational studies and subgroup analyses of randomized controlled studies (RCT) suggest that statins exert beneficial effects in patients with congestive heart failure (CHF). However, RCT that specifically evaluate the efficacy of statin treatment in patients with CHF had not been conducted. In this context, the COntrolled ROsuvastatin MultiNAtional Trial in Heart Failure (CORONA) was expected to provide new insights in this field. In the CORONA trial, 5011 elderly patients (mean age, 73 y) with moderate to severe systolic CHF of ischemic origin were randomized to receive 10 mg of rosuvastatin or placebo. After a median follow-up of 32.8 mo, rosuvastatin did not reduce the occurrence of the primary endpoint of cardiovascular death, nonfatal myocardial infarction, or stroke. Rosuvastatin also had no effect on cardiovascular mortality, a prespecified secondary endpoint. These negative findings occurred despite rosuvastatin producing the expected reductions in low-density lipoprotein–cholesterol (LDL-C) levels (–45%). There were significantly fewer hospitalizations for cardiovascular causes or for worsening CHF in the rosuvastatin group than in the placebo group (P < .001 and P = .01, respectively). However, rosuvastatin did not improve

Outcomes of Using High- or Low-Dose Atorvastatin in Patients 65 Years of Age or Older with Stable Coronary Heart Disease

Increased life expectancy is associated with an increase in the burden of chronic cardiovascular disease. To assess the efficacy and safety of high-dose atorvastatin in patients 65 years of age or older. A prespecified secondary analysis of the Treating to New Targets study, a randomized, double-blind clinical trial. 256 sites in 14 countries participating in the Treating to New Targets study. 10,001 patients (3809 patients > or =65 years of age) with coronary heart disease (CHD) and low-density lipoprotein cholesterol levels less than 3.4 mmol/L (<130 mg/dL). Patients were randomly assigned to receive atorvastatin, 10 or 80 mg/d. The primary end point was the occurrence of a first major cardiovascular event (death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke). In patients 65 years of age or older, absolute risk was reduced by 2.3% and relative risk by 19% for major cardiovascular events in favor of the high-dose atorvastatin group (hazard ratio, 0.81 [95% CI, 0.67 to 0.98]; P = 0.032). Among the components of the composite outcome, the mortality rates from CHD, nonfatal non-procedure-related myocardial infarction, and fatal or nonfatal stroke (ischemic, embolic, hemorrhagic, or unknown origin) were all lower in older patients who received high-dose atorvastatin, although the difference was not statistically significant for each individual component. The improved clinical outcome in patients 65 years of age or older was not associated with persistent elevations in creatine kinase levels. Because the study was a secondary analysis, the findings should be interpreted within the context of the main study results. The analysis suggests that additional clinical benefit can be achieved by treating older patients with CHD more aggressively to reduce low-density lipoprotein cholesterol levels to less than 2.6 mmol/L (<100 mg/dL). The findings support the use of intensive low-density lipoprotein cholesterol-lowering therapy in high-risk older persons with established cardiovascular disease. Click here for related information on atorvastatin.

High-dose atorvastatin causes regression of endometriotic implants: a rat model

This prospective randomized-controlled animal study was designed to determine the effects of atorvastatin on experimentally induced endometriosis in a rat model. Thirty-seven Wistar-Albino rats in which endometriotic implants were induced were randomly divided into four groups. Group I (Low-dose atorvastatin group, eight rats) were given 0.5 mg kg(-1) day(-1) oral atorvastatin. Group II (High-dose atorvastatin group, 10 rats) were given 2.5 mg kg(-1) day(-1) oral atorvastatin. Group III were given a single dose of 1 mg kg(-1) s.c. leuprolide acetate (GnRH agonist group, nine rats). Group IV were given no medication and served as controls (10 rats). All rats received the treatment for 21 days and were then euthanized to assess the implants' size, vascular endothelial growth factor (VEGF) level in peritoneal fluid and histological score. At the end of the treatment, the mean areas of implants were smaller and VEGF levels in peritoneal fluid were lower in Groups II and III than those in Group I and the control group (all P < 0.05). The mean areas of implants decreased from 41.2 +/- 13.9 to 22.7 +/- 13.9 mm(2) after medication in Group II and decreased from 41.2 +/- 18.1 to 13.1 +/- 13.8 mm(2) in Group III (both P < 0.05), whereas in Group I, the mean area increased from 43.0 +/- 12.7 to 50.5 +/- 13.9 mm(2) (P < 0.05). High-dose atorvastatin caused a significant regression of endometriotic implants.

Comparison of Intensive and Moderate Lipid Lowering With Statins After Acute Coronary Symptoms

background Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. methods We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). results The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan–Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. conclusions Among patients who have recently had an acute coronary syndrome, an intensive lipidlowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.