Effects of atorvastatin on low-density lipoprotein cholesterol phenotype and C- … (original) (raw)
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American Journal of Cardiology, 2007
on behalf of the Treating to New Targets (TNT) Steering Committee and Investigators High-dose statin therapy has been demonstrated to provide incremental benefit when lowdensity lipoprotein (LDL) cholesterol concentrations are lowered well below recommended target levels. This secondary analysis of the Treating to New Targets (TNT) study was conducted to investigate whether the attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations and whether any incremental benefit was achieved without additional safety risk. Patients with coronary heart disease and LDL cholesterol levels <130 mg/dl (3.4 mmol/L) were randomized to therapy with atorvastatin 10 mg/day (n ؍ 5,006) or 80 mg/day (n ؍ 4,995). The primary end point was the occurrence of a first major cardiovascular event. Clinical outcomes and safety data were compared across on-treatment LDL cholesterol quintiles. There was a highly significant reduction in the rate of major cardiovascular events with descending achieved levels of on-treatment LDL cholesterol (p <0.0001 for trend across LDL cholesterol). Analysis of individual components of the primary end point demonstrated similar results. Death from any cause and from noncardiovascular causes was lowest in patients with the lowest on-treatment LDL cholesterol levels. Cardiovascular deaths were also reduced with lower levels of on-treatment LDL cholesterol. There were no clinically important differences in adverse event rates across quintiles. Specifically, no increase in muscle complaints, suicide, hemorrhagic stroke, or cancer deaths was observed at the lowest LDL cholesterol levels.
The American Journal of Cardiology, 2008
Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipoprotein (HDL) and its subclasses. Our purpose in this post hoc subanalysis of an open-label study was to compare the effects of daily oral doses of rosuvastatin 40 mg with atorvastatin 80 mg over a 6-week period on direct LDL cholesterol and small dense LDL (sdLDL) cholesterol in 271 hyperlipidemic men and women versus baseline values. Rosuvastatin was significantly (p <0.01) more effective than atorvastatin in decreasing sdLDL cholesterol (؊53% vs ؊46%), direct LDL cholesterol (؊52% vs ؊50%), total cholesterol/HDL cholesterol ratio (؊46% vs ؊39%), and non-HDL cholesterol (؊51% vs ؊48%), The magnitude of these differences was modest, and the 2 statins caused similar decreases in triglyceride levels (؊24% and ؊26%). In conclusion, our data indicate that the 2 statins, given at their maximal doses, significantly and beneficially alter the entire spectrum of lipoprotein particles, but that rosuvastatin is significantly more effective than atorvastatin in lowering direct LDL cholesterol and sdLDL cholesterol. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:315-318)
Current Medical Research and Opinion, 2004
To investigate the relationship between changes in high density lipoprotein cholesterol(HDL-C) levels after statin treatment and the risk for coronary heart disease (CHD)-related events in the secondary CHD prevention GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. These findings suggested that dose titration with atorvastatin (10-80 mg/day, mean 24 mg/day)achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality, in comparison to usual care. Analysis of variance was used to assess the effect of atorvastatin on HDL-C over time (up to 48 months) in 1600 CHD patients. The time-dependent multivariate Cox predictive model,involving backward stepwise logistic regression,was used to evaluate the relation between coronary events and HDL-C changes. The mean increase in HDL-C levels during the study was 7%. All doses of atorvastatin significantly increased HDL-C levels. Increases were greater in men (7.8 vs 6.1%; p = 0.02), in combined hyperlipidaemia (7.9 vs 6.4% for hypercholesterolaemia; p = 0.04), and in the lower baseline HDL-C quartile (9.2 vs 5.3%, 1st vs 4th quartile; p = 0.001). After adjustment for 24 predictors of coronary events, multivariate analysis revealed a Hazards Ratio of 0.85 (95% confidence interval 0.76-0.94; p = 0.002) for every 4 mg/dL(0.1 mmol/L) increase in HDL-C. There was a significant beneficial effect on HDL-C levels across the dose range of atorvastatin. Clinical outcomes in the structured care arm of GREACE were determined in part by the extent of atorvastatin-induced HDL-C increase. This effect was independent from benefit induced by low density lipoprotein cholesterol (LDL-C)reduction, suggesting that the CHD risk reduction associated with a rise in a low HDL-C at baseline remains significant under aggressive (-46%) LDL-C lowering conditions. However, the relationship between HDL-C and vascular risk may be weaker when LDL-C levels are aggressively lowered.
Effects of Low-Dose Atorvastatin and Rosuvastatin on Plasma Lipid Profiles
American Journal of Cardiovascular Drugs, 2008
Background and objective: Despite the favorable effects of reduction of low-density lipoprotein-cholesterol Abstract (LDL-C) levels in decreasing the risk of coronary heart disease, many patients treated with lipid-lowering HMG-CoA reductase inhibitors (statins) do not achieve goal LDL-C levels. This may be due to high doses of statins prescribed that could potentially induce adverse effects and compromise patient safety and compliance with considerable expense in the long-term. We compared the actions of rosuvastatin and atorvastatin, administered at the low dosages of 10 and 20 mg/day, respectively, in reducing plasma LDL-C levels and their effects on other components of the atherogenic lipid profile in patients with primary hypercholesterolemia. Methods: In this randomized, parallel group, open-label clinical study, 106 patients with LDL-C >200 mg/dL were treated with rosuvastatin 10 mg/day (group A; n = 52), or atorvastatin 20 mg/day (group B; n = 54) for 48 weeks. Results: At 48 weeks, rosuvastatin 10 mg/day was associated with a significantly greater reduction in plasma LDL-C levels compared with atorvastatin 20 mg/day (-44.32% vs-30%; p < 0.005). Compared with atorvastatin, rosuvastatin also produced a greater reduction in plasma total cholesterol, triglycerides, and non-high-density lipoprotein-cholesterol (non-HDL-C) levels (p < 0.005). Plasma HDL-C levels were not affected significantly, independent of the drug used. Conclusion: In high-risk patients with primary hypercholesterolemia, rosuvastatin 10 mg/day was more efficacious than atorvastatin 20 mg/day in reducing plasma LDL-C levels, enabling goal LDL-C levels to be achieved and improving other lipid parameters. Both treatments were well tolerated over 48 weeks.
International Journal of Cardiology, 2005
Background: The presence of increased levels of small dense (sd) LDL (phenotype B) is associated with a substantial increase of cardiovascular disease risk. Since lowering of plasma low-density lipoprotein-cholesterol (LDL-C) by statins involves an up-regulation of the LDL receptor, we questioned whether LDL lowering by atorvastatin affects different LDL subfractions equally. Methods: Fifty-four hypercholesterolemic patients, requiring treatment for prevention of coronary heart disease received atorvastatin (10, 20 or 40 mg/day), either as initial therapy (n=33), or as replacement therapy (n=21) for pravastatin or simvastatin (both at 40 mg/day). In addition to plasma lipid measurements, cholesterol LDL subfractions were separated and analysed before and after 3 months of treatment.
Molecular and cellular biochemistry, 2000
Atorvastatin is an established HMG-CoA reductase inhibitor which effectively reduces the plasma low density lipoprotein (LDL)-cholesterol level in hyperlipidemic patients. The present study was designed to investigate whether atorvastatin treatment can modify the biochemical content of oxidized LDL in hyperlipidemic patients and the ability of oxidized LDL to impair the endothelium-dependent relaxation of blood vessels. With atorvastatin (10 mg/day) treatment for 4 weeks in 19 type IIa hyperlipidemic patients, total cholesterol level was lowered by 23%, LDL-cholesterol was lowered by 32% and triacylglycerol was lowered by 19% as compared with dietary therapy alone. High density lipoprotein levels increased by approximately 9%. The ability of oxidized LDL from hyperlipidemic patients after atorvastatin treatment to impair the endothelium-dependent relaxation was significantly reduced as compared with dietary intervention alone. Analysis of the biochemical contents of oxidized LDL fro...
Effects of atorvastatin on the HDL subpopulation profile of coronary heart disease patients
The Journal of Lipid Research, 2002
We investigated the effects of atorvastatin on the lipid and the apoA-I-containing HDL subpopulation profiles in 86 patients with established coronary heart disease (CHD). The entire drug treatment period lasted 12 weeks (4-week periods of 20 then 40, then 80 mg/day). Each dose of atorvastatin treatment resulted in significant reductions in plasma total-C, LDL-C, and triglyceride (TG), and nonsignificant increases in HDL-C levels compared with placebo treatment. ApoA-I levels did not change significantly during any of the treatment periods. Despite the modest increase of HDL-C (6%, 7%, 5%) and no change in apoA-I levels, the distribution of the apoA-I-containing HDL subpopulations changed significantly during each treatment period. There were significant increases in the concentrations of the large LpA-I ␣ -1 (24%, 39%, 26%) and pre ␣ -1 (51%, 61%, 63%) subpopulations at the expense of the small lipoprotein LpA-I:A-II ␣ -3 subpopulations which decreased on all doses, and the decreases were significant on the 40 and 80 mg/day doses (6%, 5%).
American Journal of Cardiology, 2002
This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol >4.14 mmol/L (160 mg/dl) and <6.47 mmol/L (250 mg/dl) and triglycerides <4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n ؍ 132), rosuvastatin 5 mg (n ؍ 128), rosuvastatin 10 mg (n ؍ 129), or atorvastatin 10 mg (n ؍ 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (؊40% and ؊43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated. ᮊ2002
Lipid modifying action of atorvastatin in escalating doses in patients of coronary artery disease
International Journal of Basic & Clinical Pharmacology, 2014
India is passing through an epidemic of coronary artery disease (CAD) and it is expected to be the most important cause of mortality in India by the year 2015. 1 The usual lipid profile prevalent in Indians is relatively low high-density lipoprotein cholesterol (HDL-C) and high triglycerides (TG) with normal or slightly elevated low-density lipoprotein cholesterol (LDL-C). 2 Statin-mediated lowering of LDL-C is regarded as the foundation of lipid-modifying therapy. However, this has failed to reduce cardiovascular event rates more than 20-40% relative to placebo 3 indicating the need for comprehensive lipid modification as well as control of nonlipid risk factors to combat the residual risk. Since low levels of HDL-C are established as a strong independent risk factor for cardiovascular disease (CVD), lifestyle modification and pharmacological measures must be taken together to achieve the target. 4 Atorvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase lowers LDL-C significantly, but has very little impact on HDL-C. It is frequently used in doses 10 mg, 20 mg, 40 mg and 80 mg for different levels of LDL-C elevation at baseline and the magnitude of associated major adverse cardiac event risk in future. 5 Various studies indicate that statins (which include atorvastatin), tend to decrease LDL-C for an additional 6% on doubling the dose at each level from 10 to 80 mg. This is popularly known as the "Rule of six," 6 but from literature search no such data for eastern Indian population could be established. Indians are expected to differ in their lipid distribution pattern as compared to their Caucasian counterpart owing partly to different genetic constitution and different lifestyle. Hence, the present study was undertaken to ascertain whether the same rule holds good for our population or not and also to assess the efficacy and ABSTRACT Background: A prospective, randomized controlled study with parallel treatment groups carried out to assess efficacy and tolerability of atorvastatin in escalating doses (10 mg, 20 mg, 40 mg and 80 mg) in modulating the lipid profile in patients of coronary artery disease in eastern Indian population and whether "Rule of six" commonly referred to in context of low-density lipoprotein (LDL) reduction by statins stands true in our population. Methods: Patients randomly allocated into four groups (n=632) as per selection criteria. Groups A, B, C, D received atorvastatin 10 mg, 20 mg, 40 mg and 80 mg, respectively once daily at bedtime, for 24 weeks after which evaluation of efficacy and tolerability was done. Comparison between groups performed with one-way ANOVA; p<0.05 considered to be statistically significant. Results: There was a significant reduction in cholesterol, LDL and triglycerides in all the groups, but between group comparisons did not reveal any significant reduction in lipid parameters between Groups C and D. "Rule of six" was not observed at higher doses of atorvastatin (40, 80 mg). Further, there was significant reduction of high-density lipoprotein (HDL) in Groups C and D, which is not accepted especially in Indian context where it is already low at baseline. Conclusion: In Indian perspective, where HDL is low, and the LDL values are not very high, escalating dose of atorvastatin does not give additional clinical benefit. On the contrary, reduction of HDL itself predicts an adverse cardiovascular outcome. Increased adverse events and burden of cost must be taken into account, while prescribing atorvastatin.