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At least 37 records · Page 2Linked to original sources
PubMed2005

Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins.

OBJECTIVE: Besides its predictive role in determining cardiovascular risk, C-reactive protein (CRP) may exert direct proatherogenic effects through proinflammatory properties. CRP is mainly produced by hepatocytes in response to interleukin-6 (IL-6) and is then released into the systemic circulation. 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors, or statins, significantly reduce cardiovascular events and mortality in patients with or without coronary artery disease and reduce plasma CRP levels in humans. However, the mechanism by which statins reduce plasma CRP levels remains unknown. METHODS AND RESULTS: In this study, we report that statins limit both protein and RNA levels of IL-6-induced CRP in human hepatocytes. These effects are reversed by l-mevalonate and mimicked by an inhibitor of the geranylgeranyltransferase. IL-6-induced CRP production requires the binding of IL-6 to its cognate receptors, which results in activation and phosphorylation of the transcription factor STAT3. We provide evidence that statins reduce this IL-6-induced phosphorylation of STAT3 in hepatocytes. CONCLUSIONS: These results demonstrate that statins reduce IL-6-induced CRP production directly in hepatocytes via inhibition of protein geranylgeranylation. We further show that statins act via inhibition of STAT3 phosphorylation. These findings furnish new evidence for direct antiinflammatory properties of statins and provide new mechanistic insight into their clinical benefits.

Anti-Inflammatory Agents↗
PubMed2006

Statin but not non-statin lipid-lowering drugs decrease fracture risk: a nation-wide case-control study.

INTRODUCTION: Discrepant results have been reported on association between treatment with lipid lowering drugs and fracture risk. Several studies have failed to demonstrate an effect of statins on bone mineral density. Therefore, the epidemiological findings of a reduced fracture risk may be due to selections bias, e.g. a healthy drug user effect. If so, the reduced fracture risk is most likely independent of type of lipid lowering drug. AIM: We assessed fracture risk in users of various lipid-lowering drugs. METHODS: In a case-control design, we compared 124,655 fracture cases with 373,962 age- and gender-matched controls. We used computerized registers to assess individual drug use and related these data to individual fracture data and information on potential confounders. RESULTS: Use of statins was associated with a reduced risk of any fracture (adj. OR 0.87; 95% CI, 0.83-0.92) and hip fractures (adj. OR 0.57; 95% CI, 0.48-0.69). Risk of hip fracture decreased with increased accumulated dose of statins. This was true in men and in women and in subjects younger and older than 65 years of age. However, fracture risk was not reduced in patients treated with pravastatin (adj. OR 1.02; 95% CI, 0.89-1.17) or non-statin lipid lowering drugs (adj. OR 0.99; 95% CI, 0.86-1.15). CONCLUSIONS: The reduced fracture risk in users of lipid lowering drugs is apparently specifically related to users of non-pravastatin statins. Our findings do not support the hypothesis of a healthy drug user effect as an explanation for the reduced fracture risk in users of statins.

Adolescent↗
PubMed2000

Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins.

Cholesterol lowering involving different therapies improves the clinical outcome of patients. To define the underlying pathomechanism, we studied whether treatment with statins was associated with changes in blood thrombogenicity, endothelial dysfunction and soluble adhesion molecule levels. Fifty hypercholesterolemic patients were treated with pravastatin (40 mg/day, n=24) or simvastatin (20 mg/day, n=26). Lipid profile and blood thrombogenicity were assessed in all patients before and after 3 months of cholesterol reducing therapy. Blood thrombogenicity was assessed as thrombus formation, perfusing non-anticoagulated blood directly from the patients' vein through the Badimon perfusion chamber (shear rate 1690/s). Endothelial-dependent vasomotor response was tested by laser-Doppler flowmeter. Soluble adhesion molecule level were measured by ELISA. Total and LDL cholesterol were reduced in the two treatment groups by statin therapy. Statin therapy was associated with a significant reduction in blood thrombogenicity and endothelium-dependent vasoresponse. No differences were observed between simvastatin or pravastatin treatment. Lipid lowering by statins had no effect on plasma levels of fibrinogen, sL-selectin, sP-selectin and sICAM-1 antigen. Cholesterol lowering by both statins reduced the increased blood reactivity and endothelial dysfunction present under hypercholesterolemia. The multiple effects of lipid lowering therapy by statins may explain the benefits observed in recent epidemiological trials.

Anticholesteremic Agents↗
PubMed2005

Efficacy of ezetimibe in patients with statin-resistant and statin-intolerant familial hyperlipidaemias.

OBJECTIVE: To investigate the efficacy of the cholesterol absorption inhibitor ezetimibe in patients with refractory familial hyperlipidaemia or intolerant to statin therapy. METHODS: This prospective study assessed the safety and efficacy of ezetimibe in 200 patients with refractory familial hyperlipidaemias not achieving a low-density-lipoprotein (LDL) cholesterol < 3 cholesterol < 3 mmol/L (116 mg/dL) including 22% intolerant to all statin therapy, many consuming intolerant to all statin therapy, many consuming sterol-containing products. RESULTS: Ezetimibe monotherapy resulted in 7% and 11% reductions in LDL-cholesterol and apolipoprotein B respectively. Ezetimibe-statin combination therapy reduced LDL-cholesterol by an additional 11 +/- 27% and apolipoprotein B by 11 (+79 to -18)%. There was a similar response between various sub-groups but a wide variation within groups with the greatest effect seen in patients groups with the greatest effect seen in patients under-responding to statins. The number of patients achieving the LDL-C target of 3 mmol/L rose from 5.5% to 18%. Non-significant effects included a 5 (+78 to -470)% reduction in triglycerides, 8 +/- 36% increment in HDL-cholesterol, 21 (+35 to -82)% reduction in C-reactive protein and a 1 (+20 to -50)% increase in alanine transaminase. No effects were seen on creatinine, creatine kinase, or insulin resistance. Fourteen patients (7%) discontinued ezetimibe: seven due to gastrointestinal side-effects, one patient developed an ezetimibe-induced hypercholesterolaemia (x 1.5), one developed ezetimibe-induced hypertriglyceridaemia (x 7) and five discontinued for other reasons. CONCLUSION: Ezetimibe is a useful addition to statins in patients with familial hyperlipidaemias but shows a highly variable response profile.

Adolescent↗
PubMed2003

Statin cardiomyopathy? A potential role for Co-Enzyme Q10 therapy for statin-induced changes in diastolic LV performance: description of a clinical protocol.

UNLABELLED: Lipid-lowering statins are thought to have a favorable safety profile. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting step of mevalonate synthesis. Mevalonate is the substrate for further synthesis of cholesterol and Co Enzyme Q10 (CoQ10). CoQ10 plays an important role during oxidative phosphorylation in the myocardial cell. Since myocardial diastolic function is a highly ATP dependent, we reasoned that early changes of diastolic function may be an early marker of ventricular dysfunction. METHODS: Patients who are to commence on statin therapy will be enrolled in the trial. Baseline measurements of plasma CoQ10, total cholesterol, LDL, HDL, CoQ10/LDL ratio, peak E, peak A velocities, E/A ratio, deceleration time, isovolumetric relaxation time, color M-mode propagation velocity will be performed and patients will then begin to take Oral atorvastatin (Lipitor, Parke-Davis) 20 mg daily for three to six months. All baseline measurement will be repeated after 3 to 6 months of statin therapy. Those patients demonstrating > 1 measurement of diastolic LV function that worsened during the 3 to 6 months of statin therapy will be supplemented with CoQ10 300 mg. daily for 3 months. A followup echocardiogram and blood CoQ10 level will be measured in patients who received CoQ10 supplementation. RESULTS: Statistical analysis will be performed using the paired t test to compare coenzyme levels and echocardiographic indices at baseline and after treatment and after supplementation.

Atorvastatin↗
PubMed2005

Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin.

There is an increasing trend among physicians to use 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in combination with other antilipidemic agents. The complementary lipid-altering effects of statins and fibric acid derivatives (fibrates) have led to an increasing use of statin/fibrate combination therapy, particularly for patients who have mixed dyslipidemia. Clinical experience indicates that there may be an increased risk of myotoxicity associated with statin/fibrate combination therapy. However, it is not known whether there are differences in the rate of myotoxicity between the use of fenofibrate and gemfibrozil in combination with statins. To evaluate this question, data from the United States Food and Drug Administration's Adverse Event Reporting System was reviewed to determine how many adverse events were reported for patients who were being treated concomitantly with statins and fibrates. The findings suggest that the use of fenofibrate in combination with statins results in fewer reports of rhabdomyolysis per million prescriptions dispensed than does the use of gemfibrozil.

Adverse Drug Reaction Reporting Systems↗
PubMed2004

The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes.

There has been persistent controversy regarding possible favorable or adverse effects of statins or of cholesterol reduction on cognition, mood and behavior (including aggressive or violent behavior), muscle function, and quality of life. The UCSD Statin Study seeks to ascertain the beneficial or adverse effects of statin cholesterol-lowering drugs on a set of noncardiac endpoints, including cognition, behavior, and serotonin biochemistry. The study will enroll 1000 subjects (minimum 20% female) of mixed ethnicity from San Diego. Subjects must be age 20 and older, postmenopausal if female, without known cardiovascular disease or diabetes, and with LDL-cholesterol between 115 and 190 mg/dl. Subjects will be randomized to a double-blind, placebo-controlled trial with assignment 1/3, 1/3, 1/3 to placebo, simvastatin 20 mg, or pravastatin 40 mg (equipotent LDL-cholesterol-lowering doses for drug arms with simvastatin and pravastatin chosen to represent the extremes of the lipophilicity spectrum) for 6 months of treatment followed by 2 months postcessation follow-up. Primary outcomes are cognition (cognitive battery), irritability/aggression (behavior measure), and serotonin (gauged by whole blood serotonin), assessed as the difference between baseline and 6 months, judging combined statin groups vs. placebo. Secondary outcomes include mood (CES-D and Wakefield depression inventory), quality of life (SF-12V), sleep (Leeds sleep scale, modified), and secondary aggression measures (Conflict Tactics Scale; Overt Aggression Scale, Modified). Cardiovascular reactivity will be examined in a 10% subset. As additional secondary endpoints, primary and selected secondary outcomes will be assessed by statin assignment (lipophilic simvastatin vs. hydrophilic pravastatin). "Reversibility" of changes, if any, at 2 months postcessation will be determined. If effects (favorable or unfavorable) are identified, we will seek to ascertain whether there are baseline variables that predict who will be most susceptible to these favorable or adverse noncardiac effects (i.e., effect modification).

Adult↗
PubMed2006

Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for 'pleiotropic' functions of statin therapy.

AIMS: Statin therapy is associated with improved endothelial vasodilator function. The clinical availability of ezetimibe, a potent novel cholesterol absorption inhibitor, enables to differentiate lipid-lowering effects from potential non-lipid-lowering (pleiotropic) mechanisms of statins. METHODS AND RESULTS: Forearm blood flow (FBF) responses to acetylcholine (ACH) and sodium nitroprusside (SNP) were measured by venous occlusion plethysmography in four prospectively defined groups of patients with stable coronary artery disease (CAD) before and after 4 weeks of lipid-lowering therapy. Group A (n=15): de novo monotherapy with 10 mg/day ezetimibe; Group B (n=15): 10 mg/day ezetimibe as an add-on to chronic simvastatin therapy with 20 mg/day; Group C (n=15): dose escalation from chronic 10 to 40 mg/day atorvastatin; and Group D (n=15): de novo monotherapy with 40 mg/day atorvastatin. After 4 weeks of therapy, LDL cholesterol levels were significantly reduced in all four groups. Neither ezetimibe monotherapy (Group A) nor ezetimibe combined with 20 mg simvastatin (Group B) was associated with an increase in ACH-mediated FBF responses after 4 weeks. In contrast, dose escalation of atorvastatin from 10 to 40 mg/day (Group C) or de novo therapy with 40 mg atorvastatin/day (Group D) was associated with a significant increase in ACH-mediated FBF responses (P<0.013). CONCLUSION: Thus, both statins and ezetimibe effectively lower LDL-levels within 4 weeks of therapy. However, only statin therapy is associated with improved endothelial vasodilator function, disclosing the relevance of pleiotropic effects of statins during short-term treatment of patients with CAD.

Acetylcholine↗
PubMed1996

Statins: within-group comparisons, statin escape and combination therapy.

The successful use of statins in major coronary prevention trials has resulted in an explosive widening of their use. In most instances, statin therapy will result in adequate and sustained lowering of lipids. Comparing equal-weight doses, simvastatin is twice as effective as pravastatin and lovastatin in LDL-cholesterol lowering, and all three are more effective than fluvastatin according to recent comparative studies. Statin monotherapy is not always effective in severe hypercholesterolemia or in mixed (combined) hyperlipidemia with marked triglyceride elevations. All statins accepted for therapeutic use can be combined with resin or fibrate. Myopathy resulting from statin-fibrate combinations is less frequent than had been thought on the basis of early reports, and these combinations can be used in long-term therapy of mixed hyperlipidemia.

Anticholesteremic Agents↗
PubMed2004

Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells: a novel vasculoprotective function of statins.

BACKGROUND: HMG-CoA reductase inhibitors (statins) are lipid-lowering drugs that also exert pleiotropic vasculoprotective effects via activation of the endothelial NO synthesis. NO induces S-nitrosylation of target proteins. S-Nitrosylation of the antioxidant enzyme thioredoxin was recently shown to enhance its activity, thereby reducing intracellular reactive oxygen species. Therefore, we investigated whether statins may exert an antioxidant activity in endothelial cells via S-nitrosylation of thioredoxin. METHODS AND RESULTS: Statins dose- and time-dependently increased the overall level of S-nitrosylated proteins in endothelial cells (atorvastatin 0.1 micromol/L, 206+/-30% increase; simvastatin 1 micromol/L, 214+/-19% increase; mevastatin 1 micromol/L, 191+/-10% increase). The increased S-nitrosylation was blocked by an NO-synthase inhibitor and mevalonate. Moreover, S-nitrosylation of thioredoxin was also significantly augmented after atorvastatin treatment. The atorvastatin-mediated increase in S-nitrosylation was associated with an enhanced enzymatic activity of thioredoxin (atorvastatin, 157+/-9% increase). This resulted in a significant reduction of intracellular reactive oxygen species within the endothelial cells. In contrast, in endothelial cells overexpressing a thioredoxin construct in which the S-nitrosylation acceptor amino acid cysteine 69 was replaced by serine [TRX(C69S)], atorvastatin did not activate the redox-regulatory activity of thioredoxin. Moreover, overexpression of the non-nitrosylatable thioredoxin TRX(C69S) abolished atorvastatin-mediated reduction of reactive oxygen species. CONCLUSIONS: Here, we demonstrate a novel antioxidant mechanism by which statins reduce reactive oxygen species in endothelial cells. Statin-mediated S-nitrosylation of thioredoxin enhanced the enzymatic activity of thioredoxin, resulting in a significant reduction in intracellular reactive oxygen species.

Amino Acid Substitution↗
PubMed2002

Tolerability of statin-fibrate and statin-niacin combination therapy in dyslipidemic patients at high risk for cardiovascular events.

Achieving recommended cholesterol and triglyceride targets for the prevention of cardiovascular events is difficult and frequently requires the use of >1 lipid-lowering medication. This study evaluated the tolerability and effectiveness of combination regimens in high-risk dyslipidemic patients resistant to monotherapy. A retrospective chart review of all patients referred to a cardiovascular risk reduction clinic over a 7.5-year period identified 136 patients who received combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus fibrate (n = 106) or a statin plus niacin (n = 30) regimen. During follow-up (mean 18.5 months), 28 patients (20.6%) discontinued combination therapy: 11 (8.1%) experienced myalgia with or without elevated creatine kinase, 3 had gastrointestinal upset, and 1 had asymptomatic creatine kinase elevation. No patient had combination therapy discontinued due to elevated liver enzymes. Medications were stopped in 8 patients for reasons other than reported adverse effects or biochemical abnormalities, and 5 patients were switched to alternate monotherapy. Mean percent change from baseline to treatment with combination therapy for total cholesterol (-35%), low-density lipoprotein cholesterol (-37%), high-density lipoprotein cholesterol (+23%), triglycerides (-62%), and total cholesterol/high-density lipoprotein cholesterol ratio (-41%) were all statistically significant (p <0.01). These results demonstrate that combination statin-fibrate and statin-niacin regimens are safe and effective in managing dyslipidemias in most patients at risk for cardiovascular events who are inadequately treated with one of these agents alone.

Cardiovascular Diseases↗
PubMed2006

Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanism for the anti-inflammatory actions of statins in rheumatoid arthritis.

Hypoxia, which leads to dysfunctional cell metabolism, and complement activation both play central roles in the pathogenesis of rheumatoid arthritis (RA). Recent studies have reported that mice deficient for the complement-inhibitory protein CD59 show enhanced susceptibility to antigen-induced arthritis and reported that statins have anti-inflammatory effects in RA. We hypothesized that the anti-inflammatory effect of statins in RA relates in part to their ability to increase CD59 expression in hypoxic conditions and therefore to reduce complement activation. Flow-cytometric analysis showed that CD59 expression on endothelial cells (EC) was unaffected by atorvastatin in normoxia (21% O2), whereas in hypoxic conditions (1% O2) an up to threefold dose-dependent increase in CD59 expression was seen. This effect of hypoxia was confirmed by treatment of EC with chemical mimetics of hypoxia. The upregulation of CD59 protein expression in hypoxia was associated with an increase in steady-state mRNA. L-Mevalonate and geranylgeraniol reversed the response, confirming a role for inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and geranylgeranylation. Likewise, inhibition by NG-monomethyl-L-arginine and NG-nitro-L-arginine methyl ester confirmed that CD59 upregulation in hypoxia was nitric oxide dependent. The expression of another complement-inhibitory protein, decay-accelerating factor (DAF), is known to be increased by atorvastatin in normoxia; this response was also significantly enhanced under hypoxic conditions. The upregulation of CD59 and DAF by atorvastatin in hypoxia prevented the deposition of C3, C9 and cell lysis that follows exposure of reoxygenated EC to serum. This cytoprotective effect was abrogated by inhibitory anti-CD59 and anti-DAF mAbs. The modulation of EC CD59 and DAF by statins under hypoxic conditions therefore inhibits both early and late complement activation and may contribute to the anti-inflammatory effects of statins in RA.

Anti-Inflammatory Agents↗
PubMed2000

Do pleiotropic effects of statins beyond lipid alterations exist in vivo? What are they and how do they differ between statins?

The inhibition of cellular proliferation, the restoration of endothelial activity, the inhibition of platelet reactivity, and an antioxidant potential are only a few examples of pleiotropic effects of statins. This review analyzes the current knowledge on the pleiotropic properties of this class of drugs and examines the relevant data that support the presence of these effects in vivo. The favorable outcome of major trials of statins has indicated that pleiotropic factors indeed play a role in cardiovascular protection. In addition, recent data indicate that many pleiotropic effects influence mechanisms that belong to the extravascular compartment, as well. Perhaps, some of these properties may eventually justify additional indications for statins and improve the treatment of other diseases, including inflammation and cancer.

Anticholesteremic Agents↗
PubMedDate not supplied

hsCRP and HDL effects of statins trial (CHEST): rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels A clinical investigation.

Inflammation contributes to the pathogenesis of coronary heart disease and elevated serum levels of C-reactive protein (CRP) are independently associated with increased coronary risk. This study assessed whether there were differences in the effects on CRP and high-density lipoprotein (HDL) cholesterol levels among patients treated with three common statins. In a prospective, observational study, 80 dyslipidemic adults without evidence of cardiovascular disease were treated with 10 mg atorvastatin (A), 20 mg simvastatin (S), or 40 mg pravastatin (P) daily. CRP and lipid profiles were assayed before and after 12 weeks of therapy; in 21 patients, CRP levels were also measured after 1 and 4 weeks. The three treatment groups experienced comparable reductions in CRP (A: 33%, S: 42%, and P: 30%) and statistically insignificant changes in HDL cholesterol levels. CRP began to decrease after 1 week of treatment, and decreased further at 4 and 12 weeks of therapy. The change in the log-transformed CRP concentration correlated with the change in the log-transformed LDL cholesterol concentration. Subjects had similar baseline CRP levels, lipid profiles, and coronary risk factors. The authors conclude that at doses achieving similar reductions in LDL cholesterol, the three statins were associated with comparable decreases in CRP without significant changes in HDL cholesterol levels. The correlation between the reductions in CRP and LDL cholesterol differs from the findings of other published studies, and should prompt further investigation of the mechanism by which statins reduce CRP.

Anticholesteremic Agents↗
PubMed2003

Statins, super-statins and cholesterol absorption inhibitors.

An elevated level of low-density lipoprotein cholesterol (LDL-C) is an independent risk factor for premature coronary heart disease (CHD), with a value of > or = 160 mg/dl designated as high-risk by the National Cholesterol Education Program Adult Treatment Panels I, II and III. Current goals of therapy for all patients with elevated LDL-C include reducing levels to: (i) < 160 mg/dl in those with < or = 1 CHD risk factor; (ii) < 130 mg/dl in those with more than or equal to 2 CHD risk factors; and (iii) < 100 mg/dl in patients with established CHD or CHD risk equivalents, one of which is diabetes. The discovery of drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in cholesterol biosynthesis, constituted a major advance in the treatment of patients with elevated plasma concentrations of LDL-C. The efficacy of statins in LDL-lowering and CHD risk reduction has clearly been demonstrated in a number of primary and secondary intervention trials. Emerging options for the treatment of patients with elevated LDL-C include the super-statins rosuvastatin and pitavastatin, as well as the cholesterol absorption inhibitor ezetimibe. This article reviews large-scale clinical trials in which statins have been used to reduce LDL-C concentrations. Studies that have examined the efficacy and safety of rosuvastatin, pitavastatin and ezetimibe will also be discussed.

Absorption↗
PubMed2003

Statins: new data in secondary prevention and diabetes. Pravastatin and simvastatin are the best-assessed statins.

The efficacy of pravastatin and simvastatin was first shown several years ago in patients with coronary heart disease. Other trials have since been published. In the HPS trial, which studied patients with coronary heart disease, other cardiovascular conditions, or diabetes, simvastatin significantly reduced the risk of death, coronary events and stroke when compared with placebo. In the ALLHAT-LLT trial, in patients with treated hypertension, pravastatin did not reduce overall mortality. In the PROSPER trial, in patients aged over 70 with cardiovascular disease or cardiovascular risk factors, pravastatin reduced the incidence of coronary events relative to placebo, but did not reduce overall mortality. Pharmacovigilance studies suggest there is no difference between these four statins in terms of their potential to cause rhabdomyolysis. Taken together, these trials show that statin use can be extended to patients with levels of LDL-cholesterol over 2.4 mmol/l (0.9 g/l) if they have coronary heart disease (and no hypercholesterolaemia), a history of ischaemic stroke, or lower-limb arterial disease. Statins can also be prescribed for diabetic patients with no signs of cardiovascular disease but whose LDL-cholesterol exceeds 3.4 mmol/l (1.3 g/l). Clinical trial data support the use of pravastatin or simvastatin in these situations, at a dose of 20 or 40 mg daily. Plasma creatine phosphokinase assay should be done if muscle symptoms occur or if the patient has a particular risk of rhabdomyolysis.

Aged↗
PubMed2001

Statin therapy and reductions in low-density lipoprotein cholesterol: initial clinical data on the potent new statin Rosuvastatin.

The utility of statins with increased potency in reducing low-density lipoprotein cholesterol (LDL-C) is indicated by evidence that aggressive LDL-C lowering is associated with increased reduction in coronary artery disease risk, and the need for such agents is illustrated by the fact that many patients currently fail to achieve LDL-C target levels during treatment with available drugs. In dose-ranging studies of patients with hypercholesterolemia, the new synthetic statin rosuvastatin (formerly ZD4522) produced significant, dose-dependent reductions in LDL-C compared with placebo across a range of doses. Reductions ranged from 34% at 1 mg per day to 65% at 80 mg per day, with linear regression analysis indicating an additional 4.5% reduction in LDL-C with each doubling of the rosuvastatin dose. Rosuvastatin treatment was well tolerated. Phase 3 clinical trials of this agent are under way.

Cholesterol, LDL↗
PubMed1979

Synthesis of all the stereoisomers of statine (4-amino-3-hydroxy-6-methylheptanoic acid). Inhibition of pepsin activity by N-carbobenzoxy-L-valyl-L-valyl-statine derived from the four stereoisomers.

Synthesis of all four stereoisomers of the novel amino acid statine, 4-amino-3-hydroxy-6-methylheptanoic acid, found in pepstatin, a potent acid protease inhibitor, has been accomplished. Carbobenzoxy-L-valyl-L-valyl-statine tripeptides derived from all four stereoisomers have been prepared and their effect on pepsin activity is compared to that of pepstatin.

Amino Acids↗