Lipitor scientific update |
|
 |
|
2010 Jun;12(6):396-406.
Neutel JM, Eaddy M, Lunacsek OE, Roberts C, Chen L, Kean AJ, Jackson JH.
From Orange County Research Center, Tustin, CA.
Predicted coronary heart disease risk reduction and dual blood pressure/cholesterol goal attainment in patients with hypertension treated in real-world clinical practice.
J Clin Hypertens (Greenwich). 2010;12:396-406. ((c))2010 Wiley Periodicals, Inc. Hypertension and dyslipidemia are highly co-prevalent, but often poorly controlled, coronary heart disease (CHD) risk factors. A retrospective cohort study was conducted between January 2004 and April 2008 to compare estimated 10-year CHD risk reduction and dual blood pressure and low-density lipoprotein cholesterol goal attainment (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III]) in patients with a first prescription for amlodipine monotherapy, co-prescribed amlodipine + statin, or single-pill amlodipine/atorvastatin. In total, 2739 patients were prescribed amlodipine monotherapy, 653 were co-prescribed amlodipine + statin, and 227 were prescribed single-pill amlodipine/atorvastatin. Baseline CHD risk was similar in all 3 cohorts (11.0%-12.5%). Relative CHD risk reduction was greater in those prescribed single-pill amlodipine/atorvastatin (24.5%) compared with amlodipine monotherapy (14.4%, P<.01), and co-prescribed amlodipine + statin (18.4%, P=.01). The findings were driven by greater dual goal attainment for patients prescribed single-pill amlodipine/atorvastatin (50.2%) compared with amlodipine monotherapy (31.7%, P<.05) and co-prescribed amlodipine + statin (37.5%, P<.05).
2010 Jun 29. [Epub ahead of print]
Krysiak R, Gdula-Dymek A, Bachowski R, Okopien B.
From the Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland
PLEIOTROPIC EFFECTS OF ATORVASTATIN AND FENOFIBRATE IN METABOLIC SYNDROME AND DIFFERENT TYPES OF PREDIABETES.
Objective. To compare extra-lipid effects of statins and fibrates in relationship with the baseline metabolic status of patients. Research Design and Methods. This study involved the group of 242 metabolic syndrome patients with or without prediabetes, randomized to atorvastatin, fenofibrate or placebo. Results. Compared to matched healthy subjects, metabolic syndrome patients exhibited higher plasma levels/activities of hsCRP, fibrinogen, factor VII and PAI-1, and exhibited enhanced monocyte cytokine release. All these abnormalities were alleviated by both atorvastatin and fenofibrate treatment. CRP-lowering and monocyte-suppressing actions were more pronounced for atorvastatin in subjects with impaired fasting glucose and for fenofibrate in patients with impaired glucose tolerance. Conclusions. The presence of prediabetes potentiates metabolic syndrome-induced abnormalities in plasma markers of inflammation, hemostasis, and in monocyte secretory function. Both atorvastatin and fenofibrate exhibit multidirectional pleiotropic effects in subjects with metabolic syndrome, the strength of which seems to be partially determined by the type of prediabetes.
2010 Jun 28;10(1):55. [Epub ahead of print]
Huang HW, He SW, Tan SQ, Su LL.
Patient with pontine warning syndrome and bilateral posterior internuclear ophthalmoplegia: case report.
ABSTRACT: BACKGROUND: Capsular warning syndrome was first described in 1993, featured with repetitive episodes of motor and/or sensory dysfunction without cortical signs. Recently, it has been demonstrated that clinically typical capsular warning syndrome can be associated with pontine infarct and the term "pontine warning syndrome" was coined. Case Presentation A 54-year-old woman with a history of hypertension was seen with profound left-sided hemiplegia. She had had 3 episodes of left-sided weakness before complete hemiplegia. Her speech was slurred. Left central facial palsy and hemiglossoplegia were presented. Her left plantar response was extensor and bilateral posterior internuclear ophthalmoplegia was seen on neurologic examination. Biochemical tests revealed hyperglycemia and dyslipidemia on the next day. MRI demonstrated an acute right paramedian pontine infarct. The patient was commenced on oral clopidogrel, atorvastatin and acarbose. After 23 days of hospitalization, she was discharged with severe left hemiplegia. CONCLUSIONS: 1) Pontine warning syndrome may be underestimated and understudied. 2) Posterior internuclear ophthalmoplegia is a rare clinical sign in cerebrovascular diseases, while it can help to locate a brainstem lesion rather than an internal capsular one. 3) Blood pressure lowing administration may be improper for patients with pontine warning syndrome.
2010 Jul 1;27(7):589-96. doi: 10.2165/11537330-000000000-00000.
Geleedst-De Vooght M, Maitland-van der Zee AH, Schalekamp T, Mantel-Teeuwisse A, Jansen P.
Lusse Pharmacy, Utrecht, the Netherlands.
Statin prescribing in the elderly in the Netherlands: a pharmacy database time trend study.
INTRODUCTION: There is some evidence that the beneficial effects of HMG-CoA reductase inhibitors (statins) in the elderly are at least comparable to the effects in middle-aged people. However, several studies have shown prescription rates of statins to be significantly lower in the elderly than in younger populations. OBJECTIVE: The aim of the present study was to monitor statin prescribing trends in the elderly in the Netherlands over time in terms of prevalence, incidence, type of statin, dose prescribed and adherence to clinical guidelines. METHODS: The database of a community pharmacy in Utrecht, which includes prescription data for approximately 11,000 people, was analysed to investigate trends in statin prescriptions from January 1999 to December 2008. The 1-year prevalence and incidence of statin use stratified by age were determined for each calendar year. Rate ratios (RRs) and 95% confidence intervals were calculated with 1999 as the reference year. Furthermore, the following trends of interest were calculated for each calendar year: the percentage of statin users prescribed simvastatin or atorvastatin, the median dose of simvastatin and atorvastatin prescribed, and the percentage of simvastatin users prescribed a dosage of 40 mg/day (which is recommended by the Dutch multidisciplinary guideline). RESULTS: The 1-year prevalence of statin use in medication users aged >or=50 years increased from 13.9% in 1999 to 22.8% in 2008 (RR 1.6; 95% CI 1.4, 1.9; p < 0.001). Overall, the lowest prevalence (5.1% in 1999 and 15.2% in 2008) and incidence rates (3.2% in 2000 and 4.2% in 2008) were found in patients aged >or=80 years. Before 2006, simvastatin was the most commonly prescribed statin, but the number of users declined as the percentage of patients with new simvastatin prescriptions decreased (from 43.4% in 2000 to 36.5% in 2005) and the percentage of patients treated with new atorvastatin prescriptions increased (from 37.7% in 2000 to 47.3% in 2005). As from 2006, when the Dutch multidisciplinary guideline for Cardiovascular Risk Management was introduced, recommending treatment with a daily simvastatin dose of 40 mg, the number of simvastatin users increased again and most treatment-naive patients were started on simvastatin (62.3% in 2006, increasing to 66.7% in 2008). The median simvastatin dose increased from 10 mg in 1999 to 20 mg in 2001, remaining at the same dose until 2008, and appeared to be related to the patient's age. From 2006, patients aged >or=80 years were the least likely group to receive the recommended dose of 40 mg simvastatin daily (10.0-20.0% of simvastatin users aged >or=80 years compared with 32.5-36.9% of simvastatin users aged 60-69 years). CONCLUSION: Despite the benefits of statin treatment previously reported in older patients, the prevalence and incidence of statin use were lower in elderly patients compared with younger patients. In addition, lower dosages of statins were prescribed. These findings suggest the beneficial effects of statins in the elderly observed in clinical trials may not be achieved in everyday practice.
2010 Jun 24. [Epub ahead of print]
Arnaboldi L, Corsini A.
Department of Pharmacological Sciences, Faculty of Pharmacy, Università degli Studi di Milano, Milan, Italy.
Do structural differences in statins correlate with clinical efficacy?
PURPOSE OF REVIEW: Statins, by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, decrease the synthesis not only of cholesterol but also of nonsteroidal mevalonate derivatives. While the first effect translates into plasma cholesterol reductions, the second is related to nonlipid-lowering (pleiotropic) properties. Purpose of this review is to assess the correlation between differences in statin structures and clinical effects. While the cardiovascular benefits of statin chronic therapy are achieved by lowering low-density lipoprotein cholesterol (LDL-C) and should be considered a class effect, the acute ones may reflect structure differences and pleiotropic properties of these drugs. RECENT FINDINGS: Clinical studies conducted in acute coronary syndrome patients suggest that some benefits achieved by early statin treatment could be related to their pleiotropic properties. Indeed, ex-vivo studies showed the ability of sera from hypercholesterolemic patients treated with a single dose of atorvastatin (but not of simvastatin), to inhibit smooth muscle cell proliferation, independently of LDL-C lowering. SUMMARY: These findings give a clinical ground to statins' potentially structure-related anti-inflammatory and pleiotropic properties, opening the possibility to control different aspects of atherosclerosis, by choosing the appropriate statin (tailored therapy), particularly in high-cardiovascular-risk patients.
2010 Jul 1;51(1):1-11.
Arrospide-Elgarresta A, Mar J, Vivancos-Mora J, Rejas-Gutiérrez J, Caro J.
Unidad de Investigación Sanitaria de Gipuzkoa Oeste, Hospital Alto Deba, 20500 Mondragon Arrasate, España.
[Cost-effectiveness analysis of using high doses of atorvastatin for the secondary stroke prevention in Spain] [Article in Spanish]
AIM: To estimate the cost-effectiveness of atorvastatin at high doses (80 mg/day) for the reduction of the risk of fatal and nonfatal stroke in patients with recent cerebrovascular accident or transient ischemic attack (TIA) and without coronary heart disease in Spain using data from the SPARCL study. PATIENTS AND METHODS: A discrete event simulation was developed to represent the natural evolution of a cohort of 1000 patients following a stroke or TIA. The risk for fatal and non fatal cardiovascular events was calculated from the clinical characteristic of patients in the SPARCL study for both treatment arms (atorvastatin 80 mg/day and placebo). Survival time, quality-adjusted-life-years (QALY), clinical events, and medical direct costs for a period of 5 years with a 3% per year discount were calculated for the two alternatives. A probabilistic sensitivity analysis was made running 1000 simulations. RESULTS: Compared to placebo, atorvastatin 80 mg/day prevented 22 strokes (14 nonfatal and 8 fatal), 22 myocardial infarctions (19 nonfatal and 3 fatal), 33 TIAs, 8 unstable angina episodes and 37 re-vascularisations per 1000 patients over 5 years. The incremental cost effectiveness ratio after 1000 simulations was 9914 euros (95% CI = 5717 to 26,082) per QALY. The acceptability curve showed 99% of the simulations falling below an acceptability threshold of 30,000 euros/QALY. CONCLUSIONS: Compared with placebo, use of high dose atorvastatin (80 mg/day) for secondary stroke prevention is not only of significant clinical benefit but can also be considered cost effective in Spain. It produces important benefits in health with an incremental cost within reasonable limits.
2009 Jun;41(3):125-8.
Pareek A, Yeole PG, Tenpe CR, Chandurkar N, Payghan R.
Department of Medical Affairs and Clinical Research, Ipca Laboratories Ltd., 142 AB, Kandivli Industrial Estate, Kandivli (West), Mumbai - 400 067, India.
Effect of atorvastatin and hydroxychloroquine combination on blood glucose in alloxan-induced diabetic rats.
OBJECTIVE: To evaluate the antihyperglycemic activity of atorvastatin and hydroxychloroquine combination in alloxan-induced diabetic rats. MATERIALS AND METHODS: Alloxan induced diabetic Wistar male rats were randomized into six groups of 6 rats each. (Normal rats, diabetic control, atorvastatin (ATV), hydroxychloroquine (HCQ), ATV 5 mg /kg + HCQ 100 mg/kg, and ATV 10 mg/kg + HCQ 200 mg/kg). The rats were treated for 9 days and blood samples were collected at baseline and end of therapy. These samples were analyzed for plasma glucose by autoanalyzer. Changes in body weight, water, food intakes and total protein content were also recorded. RESULTS: Atorvastatin and hydroxychloroquine alone and in combination reported significant fall in blood glucose level from baseline. Fall in glucose level was significantly more in high dose combination of atorvastatin and hydroxychloroquine (ATV: 10 mg/kg + HCQ: 200 mg/kg) as compared to other study treatment groups (ATV: 17% Vs HCQ: 7% Vs ATV 5mg/kg + HCQ 100mg /kg: 14% Vs ATV 10mg/kg + HCQ 200mg /kg: 21%; p<0.01). ATV and HCQ individually and in combination also improved the body weight loss. The weight gain was significantly more in combination treated rats as compared to positive control group and greater than those who received atorvastatin and hydroxychloroquine alone. Rats treated with the combination also reported significant decrease in food intake and significant increase in total protein. CONCLUSION: Increased hypoglycemic effect in combination may be due to potentiation or synergism between HCQ and ATV. Further studies are required to demonstrate clinically significant antidiabetic effect.
2009 Dec;(4):119-30.
Declerck E, De Loof H, De Meyer GR.
Laboratoire de Pharmacologie, Université d'Anvers, Campus Drie Eiken, Universiteitsplein 1, Antwerpen, Wilrijk.
[Statins under fire: justified or not?] [Article in French]
Statins inhibit the synthesis of cholesterol in the liver resulting in a decrease of LDL cholesterol and triglycerides, and a limited increase in HDL cholesterol. Statins also have pleiotropic effects, such as stabilisation of atherosclerotic plaques. The 4S-study was the first trial that demonstrated a significant benefit with statins in secondary prevention. The WOSCOPS-study was the first to prove the efficacy of statins in primary prevention. diseases approximately 10 years later than men. Therefore, it looks as if women are protected against cardiovascular diseases. Hence, they were underrepresented in large clinical trials. If there is no limited life expectancy, elderly--even older than 85 years--do not have to be treated differently for the secondary prevention than younger people. For primary prevention, the situation of the patient has to be evaluated, paying attention to additional risk factors. Type 2 diabetic patients that already have had a cardiovascular incident are considered to be at high risk and are eligible for an intensive therapy. Primary prevention in diabetic patients is often compared with secondary prevention in non-diabetic patients. The use of statins in children is controversial due to possible interference with the development of the child. New guidelines decrease the age for starting a therapy from 10 years old to 8 years old. For all patients a good safety profile is very important, given the long duration of therapy. Statins are used increasingly in high dose and accordingly the risk of adverse effects increases. Muscle toxicity is the most frequent side effect. The risk is strongly intensified by drug interactions through CYP3A4 (for simvastatin and atorvastatin), high doses, and combination therapy with fibrates. The use of statins during pregnancy is contra-indicated. Pharmacists are well placed to give advice about the risks of the use, or non-use, of statins. A high cholesterol level and the accompanied risk of cardiovascular disease, is something that one cannot really sense. The well-established effects of statins have to be explained to patients, together with a healthy life style. It is important to mention that the effects of statins in high--risk patients are largely proven. For primary prevention the risk factors have to be evaluated individually. Compliance is often low and pharmacists can play a major role in the pharmaceutical care of cardiovascular patients.
2009 Dec;31(12):2894-9.
Kelesidis T, Kelesidis I.
Department of Medicine, Caritas Saint Elizabeth's Medical Center, Tufts University School of Medicine Boston, Massachusetts 02135, USA.
Unexplained high fever in an elderly patient treated with clonidine, duloxetine, and atorvastatin.
BACKGROUND: Drug-induced fever is a clinical diagnosis and should always be considered when the fever is constant and high without a clear source of infection. Although drug-induced fever has been reported with other centrally acting antihypertensive drugs such as methyldopa, published reports of this adverse effect with clonidine in humans were not identified in a search of the literature. CASE SUMMARY: A 66-year-old institutionalized white female with a history of morbid obesity (body mass index, 40 kg/m2), Alzheimer's dementia, hypertension, and depression presented to a hospital in Boston, Massachusetts (Caritas Saint Elizabeth's Medical Center) with generalized weakness and shortness of breath and was found to have a non-ST segment elevation myocardial infarction. Before hospitalization, the patient was taking memantine 10 mg PO BID, donepezil 10 mg PO once daily, duloxetine 60 mg PO once daily, clonidine 0.1 mg PO TID, metoprolol 50 mg PO BID, and amlodipine 10 mg PO once daily. On admission, the patient was initiated on aspirin 325 mg, atorvastatin 80 mg, and clopidogrel 75 mg PO daily. Her dose of clonidine was increased to 0.2 mg PO TID to optimize blood pressure control, and metoprolol and amlodipine were continued at the same doses. The patient developed fever on the third day after the cardiac catheterization. The fever ranged from 99.0 degrees F to 102.7 degrees F. The physical examination, laboratory data analysis, multiple blood cultures, urinalysis, chest radiograph, and a computed tomography of the head, chest, abdomen, and pelvis did not reveal any source of infection. On the sixth day after admission, clonidine was reduced to the baseline dose of 0.1 mg PO TID and on the ninth day it was stopped. The patient was afebrile on the twelfth day and remained so for the duration of her hospitalization. Naranjo scores for her newly initiated concomitant medications were as follows: aspirin, 1; atorvastatin, 3; clonidine, 6; and clopidogrel, 1. The rating of 6 for clonidine suggests that it was probably associated with the fever in this patient. CONCLUSION: We describe a case of drug-induced fever probably associated with clonidine administration. The higher dose of clonidine alone or in interaction with duloxetine and atorvastatin may have contributed to the development of drug-induced fever. Copyright 2009 Excerpta Medica Inc. All rights reserved.
2009 Dec;31(12):2824-38.
Davidson MH, Rooney MW, Drucker J, Eugene Griffin H, Oosman S, Beckert M; LCP-AtorFen Investigators.
The University of Chicago, Pritzker School of Medicine, Chicago, Illinois, USA.
Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: a 12-week, multicenter, double-blind, randomized, parallel-group study.
BACKGROUND: Coadministration of statin and fenofibrate monotherapies is frequently used to treat patients with dyslipidemia; however, a fixed-dose combination (FDC) tablet is not currently marketed. OBJECTIVE: This study evaluates a new FDC tablet of atorvastatin 40 mg and fenofibrate 100 mg. METHODS: This was a 12-week, multicenter, double-blind, randomized, parallel-group Phase IIb study. Adults with dyslipidemia (non-HDL-C >130 mg/dL and triglycerides [TG] > or =150 but < or =500 mg/dL) were randomly assigned in a 1:1:1 ratio to receive the FDC, atorvastatin 40 mg, or fenofibrate 145 mg for 12 weeks. Study medication was taken once daily in the evening, without regard to meals. Patients attended follow-up visits after 4, 8, and 12 weeks of the double-blind treatment. The primary efficacy end points were the mean percentage changes from baseline to the final visit (week 12) in non-HDL-C, HDL-C, and TG. Secondary variables were LDL-C, VLDL-C particle concentration, total cholesterol, apolipoprotein B, lipoprotein (a), high-sensitivity C-reactive protein, fibrinogen, homocysteine, creatinine, myeloperoxidase, and lipoprotein-associated phospholipase A2. Tolerability was assessed by adverse events, laboratory parameters, vital signs, physical examinations, and ECGs. RESULTS: Patients (n = 220) were aged 26 to 87 years; 115 (52.3%) were men and 105 (47.7%) were women; 189 (85.9%) were white, 17 (7.7%) were black, and 15 (6.8%) were Hispanic or Latino; and mean (SD) weight was 200.5 (40.85) lb (range, 103.5-367.4 lb). Previous treatments were statins (25.9% [57/220]), fibrates (1.8% [4/220]), and dietary supplements (25.5% [56/220]); 57.7% (127/220) of patients were treatment naive. Use of the FDC was associated with an improvement in non-HDL-C (-44.8%) that was significantly greater than with fenofibrate monotherapy (-16.1%; P < 0.001) but was not significantly different from that with atorvastatin monotherapy (-40.2%; P = NS). HDL-C increased significantly more in the FDC group (19.7%) than with atorvastatin (6.5%; P < 0.001) but was not significantly different from fenofibrate (18.2%; P = NS). TG lowering in the FDC group (-49.1%) was significantly greater than with both atorvastatin (-28.9%; P < 0.001) and fenofibrate (-27.8%; P = 0.001). LDL-C lowering in the FDC group (-42.3%) was significantly greater than with fenofibrate (-13.9%; P < 0.001) but not significantly different from atorvastatin (-43.1%; P = NS). The FDC had either comparable or significantly greater improvements in other lipid variables and multiple secondary variables. The FDC was generally well tolerated; the tolerability profile was consistent with those of atorvastatin and fenofibrate monotherapies. Treatment-emergent adverse events (ie, those occurring after the first dose of study medication) were recorded in 43 of 73 patients (58.9%) for the FDC, 49 of 74 (66.2%) for atorvastatin, and 48 of 73 (65.8%) for fenofibrate. CONCLUSIONS: In this 12-week study, patients with dyslipidemia treated with the 40/100-mg atorvastatin/ fenofibrate FDC had a significantly greater reduction in TG than those treated with atorvastatin 40 mg or higher-dose fenofibrate 145 mg. Treatment with the FDC was also associated with a significantly greater reduction in non-HDL-C compared with fenofibrate alone and a greater increase in HDL-C compared with atorvastatin alone. All treatments were generally well tolerated. Copyright 2009 Excerpta Medica Inc. All rights reserved.
2009 Aug 25;89(32):2240-4.
Han YL, Zhang ZL, Li Y, Wang SL, Jing QM, Wang ZL, Wang DM.
Department of Cardiology, Institute of Cardiovascular Diseases, Shenyang General Hospital of PLA ,Shenyang 110016, China.
[Comparison on long-term effects of atorvastatin or pravastatin combined with clopidogrel for patients undergoing coronary stenting: a randomized controlled trial] [Article in Chinese]
OBJECTIVE: To evaluate the long-term therapeutic effects of atorvastatin via cytochrome P450 (CYP)3A4 pathway or a non-CYP 3A4 pathway statin, pravastatin, combined with clopidogrel for the patients undergoing coronary stenting. METHODS: Between February 2006 and March 2007, a total of 1275 patients undergoing successful coronary stenting were randomly assigned to receive atorvastatin 20 mg/d (n = 638) or pravastatin 20 mg/d (n = 637). All patients received standard clopidogrel therapy. The primary end point was cardiac and cerebral ischemic events at 12 months, defined as a composite of cardiac death, non-fatal myocardial infarction (MI) or stroke. The secondary end points were major adverse cardiac and cerebral events (MACCE), stent thrombosis and TIMI hemorrhagic events at 12 months. RESULTS: The baseline clinical characteristics, angiographic and PCI result were comparable between two groups. At 12 month follow-up, no significant difference was observed in cardiac and cerebral ischemic events between two groups (4.7% vs 5.5%, P > 0.05). Also no significant difference existed in rate of cardiac death (1.9% vs 2.5%, P > 0.05), non-fatal MI (0.5% vs 0.3% , P > 0.05), stroke (2.4% vs 2.7%, P > 0.05) and TVR (7.7% vs 5.5%, P > 0.05) between two groups. The rates of MACCE (12.4% vs 11.0%, P > 0.05), stent thrombosis (2.0% vs 2.5%, P > 0.05) and hemorrhagic events (13.0% vs 12.2%, P > 0. 05) were similar between two groups. CONCLUSION: The 12 month clinical outcomes were similar between patients receiving atorvastatin 20 mg/d or pravastatin 20 mg/d combined with clopidogrel after coronary stenting. It confirmed the efficacy and safety of the combination of clopidogrel with statins via different metabolic pathways.
2008 Dec;28(12):1078-81.
Yang QY, Zhao LC.
The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou.
[Effect of yiqi wenyang huoxue recipe on bone marrow stem cells' mobilization and its influence on heart function in patients with myocardial infarction] [Article in Chinese]
OBJECTIVE: To observe the effect of Yiqi Wenyang Huoxue Recipe (YWHR) on bone marrow stem cells' mobilization and heart function of myocardial infarction (MI) patients. METHODS: Sixty acute MI patients were equally assigned to the treatment group and the control group randomly according to the numeration table. Standard therapy composed of subcutaneous injection of 0.4 mL low molecular heparin every 12 h for 7 successive days combined with continuously orally taken of enteric-coated aspirin tablets 0.1 g, Perindopril 4 mg and Atorvastatin 10 mg once a day (if there was no contraindication), was given to all patients. But to the treatment group, one dose of YWHR was given every day additionally, which consisted of Panax ginseng 10 g, Radix Astragali 15 g, Radix Aconiti lateralis preparata 5 g, Radix Ilex pubesceus 30 g and Herbal Leonuri 10 g for 10 successive days. The change of CD34+ cells' count was observed. The infarcted area size was estimated with QRS scoring system at the end of the 3rd week after onset, and the heart function parameters, including left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index (LVESVI), left ventricular end-diastolic volume index (LVEDVI) and wall motion score index (WMSI), were measured with ultrasonic cardiogram. RESULTS: On the fifth and tenth day, the peripheral CD34+ cell count in the treatment group (48.26 +/- 5.74 and 34.18 +/- 6.70) were significantly higher than that on the day of admission (20.33 +/- 6.01), also higher than the corresponding count in the control group (22.45 +/- 5. 31 and 19.89 +/- 5.93), showing statistical difference (P < 0.01). The QRS score (2.68 +/- 0.41) and infarcted area (22.54 +/- 2.49)% in the treatment group were lower than those in the control group (3.96 +/- 0. 34 and 29.38 +/- 2.59) respectively. Comparison of heart function parameters between groups showed that LVEF (0.59 +/- 0.07 vs. 0.50 +/- 0.07) was higher LVEDVI (68.92 +/- 11.52 vs. 78.46 +/- 13.16), LVESVI (27.47 +/- 7.86 vs. 36.71 +/- 8.85), and WMSI (2.10 +/- 0.11 vs. 2.98 +/- 0.12) were lower in the treatment group than those in the control group respectively, also showing statistical difference (all P < 0.01). CONCLUSION: YWHR has a good effect on bone marrow stem cell mobilization, it can reduce the infarcted area and improve the heart function of patients with acute MI.
2008 May-Jun;60(3):215-22.
Harikrishnan S, Rajeev E, Tharakan JA, Titus T, Ajit Kumar VK, Sivasankaran S, Krishnamoorthy KM, Nair K.
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
Efficacy and safety of combination of extended release niacin and atorvastatin in patients with low levels of high density lipoprotein cholesterol.
OBJECTIVE: We investigated the safety and efficacy of combination therapy of extended release (ER) niacin and atorvastatin in patients with low HDL-C and compared the results with atorvastatin monotherapy. METHODS: This open label study recruited consecutive men and women who had coronary artery disease with HDL-C levels <35 mg/dL. These patients were already on atorvastatin therapy targeted to lower low density lipoprotein cholesterol (LDL-C), for a minimum period of 6 months. Group 1, n = 104 (mean age 52.7 years) received ER niacin in addition to atorvastatin and group 2 (n = 106) continued on atorvastatin (mean age 52.3 years). ER niacin dose was built up to a maximum of 1.5 g and atorvastatin dose titrated according to LDL levels in both the groups. The lipoprotein levels at baseline were similar (p = NS). RESULTS: At 9 +/- 1.8 months of follow-up, the mean dose of ER niacin was 1.3 g and atorvastatin 13.2 mg in group 1. In comparison, group 2 patients had mean atorvastatin dose of 15.9 mg. Patients in group 1 had significant elevation in HDL-C cholesterol (39.5 +/- 5.5 vs 35.7 +/- 4.5 mg/dL), reduction in total cholesterol (156.4 +/- 31 vs 164.5 +/- 39.3 mg/dL) and also LDL-C (88.9 +/- 28.3 vs 99.8 +/- 35.4 mg/dL) compared to group 2 (all p < 0.05). The magnitude of reduction in triglyceride levels was not significant between the groups (140.1 +/- 40.4 vs 145.2 +/- 46.5 mg/dL) (p = NS). No major adverse events or clinical myopathy occurred in either groups. Four patients (4%) discontinued ER niacin (2 due to gastro-intestinal symptoms and 2 due to worsening of diabetes). Flushing occurred in 3% patients, but none felt it to be troublesome. CONCLUSION: Adding ER niacin to atorvastatin exhibited beneficial effects on lipid profile with significant elevation of HDL-C cholesterol and further lowering of LDL-C compared to monotherapy. This treatment offered better targeted therapy and was well tolerated with proper monitoring in Indian patients.
2008 Oct;84(4):488-96.
Kalliokoski A, Backman JT, Kurkinen KJ, Neuvonen PJ, Niemi M.
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Effects of gemfibrozil and atorvastatin on the pharmacokinetics of repaglinide in relation to SLCO1B1 polymorphism.
In a randomized crossover study, 24 SLCO181-genotyped healthy volunteers were given daily doses of 1,200 mg gemfibrozil, 40 mg atorvastatin, or placebo, followed by 0.25 mg of repaglinide on day 3. The mean increase in the repaglinide area under the plasma concentration-time curve from 0 h to infinity (AUC(0-infinity)) produced by gemfibrozil was larger in individuals with the SLCO1B1 c.521CC genotype (n = 6) than in those with the c.521TC (n = 6) and c.521TT (n = 12) genotypes, by factors of 1.56 (P = 0.004) and 1.54 (P = 0.002), respectively. Gemfibrozil prolonged the repaglinide elimination half-life 1.43 times more in the c.521 CC group than in the c.521TT group (P = 0.047), but no differences were seen in the effects on peak plasma concentration (C(max)). While on gemfibrozil, the minimum blood glucose concentration after repaglinide intake was 19% lower in the c.521CC participants than in the c.521TT participants (P = 0.009). In the c.521TT group, atorvastatin intake had the effect of increasing repaglinide Cmax and AUC(0-infinity) by41% (P = 0.001) and 18% (P = 0.033), respectively. In conclusion, the extent of gemfibrozil-repaglinide interaction depends on SLCO1B1 genotype. Atorvastatin raises plasma repaglinide concentrations, probably by inhibiting organic anion transporting polypeptide 1B1 (OATP1B1).
2008 Dec;118(12):747-55.
Hart RG.
Vascular Neurology, Department of Neurology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
What's new in stroke? The top 10 studies of 2006-2008. Part II.
Six studies from 2006-2008 that have influenced clinical management of stroke and threatened stroke are presented. The ABCD2 score effectively stratifies the short-term risk of stroke following transient ischemic attack into those with a high (12%), moderate (6%), and low (1%) 7-day stroke risk. High-dose atorvastatin reduces recurrent stroke in patients with recent stroke, but probably slightly increases central nervous system hemorrhage (SPARCL). Intravenous tissue plasminogen activator is of overall benefit to selected patients when given 3 to 4.5 hours after ischemic stroke onset (ECASS III). Adjusted-dose warfarin is far superior to aspirin and is relatively safe for very old people with atrial fibrillation (BAFTA). Despite results from 3 recent randomized trials (SAPPHIRE, EVA-3S and SPACE) the optimal role of carotid angioplasty/stenting vs. endarterectomy remains unclear. Enoxaparin once daily is an efficacious alternative to unfractionated heparin twice daily for prevention of venous thromboembolism after acute ischemic stroke (PREVAIL). These recent studies add important pieces to the complex puzzle of optimal stroke prevention and treatment.
2008 Dec;30(12):2298-313.
Bonnet J, McPherson R, Tedgui A, Simoneau D, Nozza A, Martineau P, Davignon J; CAP Investigators.
Hôpital du Haut-Lévèque, Pessac, France.
Comparative effects of 10-mg versus 80-mg Atorvastatin on high-sensitivity C-reactive protein in patients with stable coronary artery disease: results of the CAP (Comparative Atorvastatin Pleiotropic effects) study.
BACKGROUND: The major beneficial effect of statins- reducing the risk for coronary events-has primarily been ascribed to reductions in low-density lipoprotein cholesterol (LDL-C) but may in part be related to a direct antiinflammatory action (ie, decreased high-sensitivity C-reactive protein [hs-CRP] concentration). OBJECTIVES: The objectives of this CAP (Comparative Atorvastatin Pleiotropic Effects) study were to compare the effects of low- versus high-dose atorvastatin on hs-CRP concentrations and to determine the relationship between changes in LDL-C and hs-CRP concentrations in patients with coronary artery disease (CAD), low-grade inflammation, and normal lipoprotein concentrations. METHODS: This multicenter, prospective, randomized, double-blind, double-dummy study was conducted at 65 centers across Canada and Europe. Patients with documented CAD, low-grade inflammation (hs-CRP concentration, 1.5-15.0 mg/L), and a normal-range lipid profile (LDL-C concentration, 1.29-3.87 mmol/L [50-150 mg/dL]; triglyceride [TG] concentration, <4.56 mmol/L [<400 mg/dL]) were randomly assigned to receive 26-week double-blind treatment with atorvastatin 10 or 80 mg QD. Investigators were to aim for the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C target of <2.59 mmol/L (<100 mg/dL). The primary end point was the percentage change from baseline in hs-CRP, as measured at baseline and weeks 5, 13, and 26 using high-sensitivity, latex microparticle-enhanced immunoturbidimetric assay. Changes from baseline in LDL-C, as measured directly in serum at the same time points, were also calculated. The secondary efficacy variables included the percentage changes from baseline in lipid parameters (LDL-C, high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], TG, apolipoprotein B, non-HDL-C, and TC:HDL-C ratio) at 5, 13, and 26 weeks of treatment. Tolerability was assessed using physical examination, including vital sign measurement, and laboratory analyses. RESULTS: A total of 339 patients were enrolled (283 men, 56 women; mean age, 62.5 years; weight, 81.3 kg; 10-mg/d group, 170 patients; 80-mg/d group, 169). No significant differences in baseline demographic or clinical data were found between the 2 treatment arms. In the 10-mg group, hs-CRP was decreased by 25.0% at 5 weeks and remained stable thereafter (%Delta at week 26, -24.3%; P < 0.01). In the 80-mg group, hs-CRP was decreased by 36.4% at 5 weeks and continued to be decreased over the study period (%Delta, -57.1% at week 26; P < 0.001 vs baseline). At 5 weeks, LDL-C was decreased by 35.9% in the 10-mg group and by 52.7% in the 80-mg group (P < 0.001 between groups) and remained stable thereafter (%Delta at week 26, -34.8% and -51.3%, respectively; P < 0.001 between groups). The NCEP ATP III LDL-C target of <2.59 mmol/L (<100 mg/dL) was reached in 77.1% of patients treated with atorvastatin 10 mg and 92.3% of those treated with 80 mg (P < 0.001). Dual targets of hs-CRP <2 mg/L and LDL-C <1.81 mmol/L (<70 mg/dL) were reached in a significantly greater proportion of patients in the 80-mg group compared with the 10-mg group (55.6% vs 13.5%; P < 0.001). The decrease in hs-CRP was largely independent of baseline LDL-C and change in LDL-C. Two serious adverse events were reported by the investigator as treatment related: acute hepatitis in the 10-mg group and intrahepatic cholestasis in the 80-mg group, in 2 patients with multiple comorbidities. Two deaths occurred during the study, both in the atorvastatin 80-mg group (1, myocardial infarction; 1, sudden death), neither of which was deemed treatment related by the investigator. CONCLUSIONS: In these patients with documented CAD, evidence of low-grade inflammation, and normal range lipid profiles, the effects of atorvastatin on changes in hs-CRP were dose dependent, with the high dose (80 mg) being associated with significantly greater reductions in hs-CRP concentrations. Both doses were associated with a significant and progressive decline in hs-CRP largely independent of changes in LDL-C, HDL-C, and TG. Clinical Trials Identification Number: NCT00163202.
2007;60 Suppl 2:28-32.
Teplan V, Schück O, Stollova M, Vitko S.
Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Metabolic syndrome after renal transplantation.
Obesity and hyperlipidemia are common findings after kidney transplantation (Tx), and may represent independent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored a total of 68 obese transplant patients (body mass index > 30 kg/m2) with dyslipidemia. We compared findings of a new therapeutic regimen 1 year (at baseline) and 2 years after renal transplantation. Using the Subjective Global Assessment, at the end of the first year an Individualized Hypoenergetic-Hypolipidemic diet was initiated. Subsequently, after withdrawal of corticosteroids IHHD was regularly supplemented with statins (atorvastatin 10-20 mg/day) and followed-up for 2 years. All patients were on a regimen of cyclosporin A or tacrolimus and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (p<0.25) and an increase in adiponectin levels (p<0.01). Long-term therapy was associated with a significant decrease in serum leptin (p<0.01) and lipid metabolism parameters (p<0.01). Insulin clearance mean systolic and diastolic blood pressure, proteinuria and apo-lipoprotein E isoforms did not differ significantly. Based on our results, we can assume that obesity and hyperlipidemia after renal transplantation can be effectively treated by modified immunosuppression (corticosteroid withdrawal), statins and long-term diet (IHHD). The increased levels of adiponectin may be a marker of reduced atherosclerosis and chronic allograft nephropathy.
2007;14(3):232-7.
Jankowski P, Loster M, Kawecka-Jaszcz K.
Ezetimibe: New perspectives in lipid lowering treatment.
Therapeutic goals for lipid lowering treatment in the prevention of ischemic heart disease are often not reached in clinical practice. Even the highest doses of statins do not guarantee good control of hypercholesterolemia in all patients. Therefore, new lipid lowering drugs are being investigated. One of them is ezetimibe - intestinal cholesterol absorption inhibitor. Treatment with ezetimibe results in significant reduction of total cholesterol and LDL cholesterol levels. It is hoped that concomitant treatment with ezetimibe and other lipid lowering drugs (particularly statins) will be more effective. In large randomized clinical trials, co-administration of ezetimibe with atorvastatin and simvastatin proved to be more effective in lowering cholesterol levels and reaching target therapeutic levels than treatment with statin alone. In addition, combined treatment with ezetimibe and simvastatin was more effective compared to treatment with today's most effectively used statin (rosuvastatin) alone. Reduction of statin dose, due to the combined treatment with ezetimibe, lowers the risk of adverse events. Results of the published studies suggest that ezetimibe is safe and when administered together with statin does not increase the risk of liver or muscle damage. Treatment with ezetimibe may be regarded as a new option in the management of patients who need lipid lowering treatment. (Cardiol J 2007; 14: 232-237).
2007 Dec;28(2):137-48.
Jurukovska-Nospal M, Arsova V, Levchanska J, Sidovska-Ivanovska B.
Institute for Heart Diseases, Clinical Centre, Skopje, Medical Faculty, Ss Cyril and Methodius University, Skopje, R.Macedonia
Effects of statins (atorvastatin) on serum lipoprotein levels in patients with primary hyperlipidemia and coronary heart disease.
The aim of our study was to investigate the effects of atorvastatin on serum levels of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) in patients with primary hyperlipidemia and established coronary heart disease. MATERIAL AND METHODS: A group of 96 patients (pts), of both sexes, aged 34-59, with primary hyperlipidemia and coronary heart disease were monitored at baseline and 12 times within 12 months by the measurement of total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and lipoprotein (a) were monitored at baseline, after 6 months and after 12 months of atorvastatin therapy. The analyses were performed in the laboratory of the Clinical Biochemistry Institute of the Clinical Centre in Skopje. Serum levels of TC were evaluated using the calorimetric method, LDL was calculated according to Friedewald's formula, and HDL was determined with a precipitation test. Serum levels of apoA1, apoB and lipoprotein (a) were measured by the immunoturbidimetric method. The therapeutic doses of atorvastatin used were 40 mg. Liver enzymes, alanine aminotransferase (AST), aspartate aminotransferase (ALT) and creatine kinase (CPK) level were also monitored in our patients. RESULTS: According to our results, total cholesterol (TC), low-density lipoprotein (LDL) and apolipoprotein B (apoB) levels decreased after treatment by 43.58%, by 41.46%, and by 6,8%; high-density lipoprotein (HDL) increased insignificantly by 4%, apolipoprotein A1 (apoA1) and lipoprotein (a) remained unchanged. CONCLUSION: The significant reduction of total serum cholesterol, LDL, and apoprotein B levels achieved represents the good result of the atorvastatin therapy, as opposed to the effects on HDL values, which showed no significant increase. Serum apolipoprotein A1 levels and serum lipoprotein (a) levels remainned unchanged at baseline and after 12 months of atorvastatin therapy, and they remained stable over time. This probably means that atorvastatin has no therapeutic effect on the two parameters investigated. Elevation in alanine aminotransferase and aspartate aminotransferase levels greater than twice the upper limit of normal were seen in only one patient, after 12 months of atorvastatin therapy. Creatine kinase levels remained stable over time.
2007;45(2):193-9.
Dobreanu M, Dobreanu D, Fodor A, Bacarea A.
Department of Clinical Biochemistry-Immunology, University of Medicine and Pharmacy, Târgu Mureş, Romania.
Integrin expression on monocytes and lymphocytes in unstable angina short term effects of atorvastatin.
Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events. The most powerful class of lipid-lowering drugs available-statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors)--have additional actions, unrelated to cholesterol reduction, including anti-inflammatory and immunomodulatory properties. This study sought to determine if atorvastatin affects monocyte and lymphocyte activation in patients with unstable angina and mild primary hypercholesterolemia. Following a 4-weeks hypolipemiant-free baseline period, 22 patients-12 with unstable angina (UA) and 10 patients with stable coronary heart disease (SCHD) - were treated with Atorvastatin 20 mg/day. Lipopolysaccharide (LPS)-receptor (CD14) and HLA-DR expression on monocytes and beta-integrins (CD11b, 11c, 49d) on monocytes and lymphocytes were measured by flow cytometry before and after treatment with atorvastatin for 8 weeks. Monocyte CD11b, 11c and CD14 expression and T lymphocytes CD11b expression were significantly (p < 0.001) higher in UA patients before treatment when compared with that in SCHD patients. In patients with UA, they decreased markedly with atorvastatin treatment. The reduction in expression of adhesion molecule on monocytes and lymphocytes and the concentrations of CRP and sICAM-1 may crucially contribute to the clinical benefit of atorvastatin in coronary artery disease, independent of cholesterol lowering effects.
2007;47(4):37-40.
Pirkova AA, Samoĭlova EV, Ameliushkina VA, Kaminnyĭ AI, Titov VN, Prokazova NV, Naumov VG, Kucharchuk VV, Korotaeva AA.
[Effect of atorvastatin therapy on the level of secretory phospholipase A2 group IIA and on the modification of low density lipoproteins in patients with ischemic heart disease] [Article in Russian]
We studied effect of atorvastatin on secretory phospholipase A2 group IIA (sPLA2-IIA) in blood serum of patients with ischemic heart disease (IHD), lipid composition of low density lipoproteins (LDL) and process of modification of LDL induced by sPLA2-IIA in 20 patients taking 20 mg/day of atorvastatin for 3 months. In patients with initially high level of sPLA2-IIA ( > 8 mcg/l) its concentration significantly decreased. Amount of total cholesterol, triglyceride, lecithin, and lysolecithin remained unchanged, however in equimolar relations there occurred decrease of amount of total cholesterol and increase of cholesterol esters. At incubation of LDL, extracted from patient s plasma before initiation of the study, with human sPLA2-IIA from cardiac myxoma, 3.5 nmol of lysolecithin per 1 mg of LDL protein was formed while at incubation of LDL of same patients, extracted after 3 months of atorvastatin administration, amount of lysolecithin was 1.54 nmol/mg LDL protein. Thus atorvastatin therapy causes lowering of sPLA2-IIA in patients with initially high blood level of the enzyme and to a great extent precludes sPLA2-IIA induced LDL modification.
ScienceDaily (Nov. 18, 2009)
Prevalence of High LDL, or 'Bad' Cholesterol Levels Decreases in US
According to a study in the November 18 issue of JAMA. But a high percentage of adults still are not being screened or treated for high cholesterol levels.
Elevated levels of low-density lipoprotein cholesterol (LDL-C), the major atherogenic lipoprotein, are a primary focus for cholesterol management of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). "The guidelines set LDL-C target levels that are based on the history of coronary heart disease (CHD) or risk for developing CHD in the next 10 years," the authors write. Few studies have described the prevalence of high LDL-C levels and the use of lipid-lowering medications across all CHD risk categories, according to background information in the article.
Elena V. Kuklina, M.D., Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues investigated trends in the prevalence of screening, current use of cholesterol-lowering medication, and high LDL-C levels across 4 study cycles (1999-2000, 2001-2002, 2003-2004, and 2005-2006). The researchers used data from the National Health and Nutrition Examination Survey (NHANES), and restricted the study sample to fasting participants age 20 years or older (n = 8,018), excluded pregnant women (n = 464) and participants with missing data (n = 510), with the final study sample consisting of 7,044 participants.
Overall prevalence for high LDL-C levels decreased from 31.5 percent in 1999-2000 to 21.2 percent in 2005-2006. "However, this prevalence varied substantially by risk category. The highest prevalence of high LDL-C levels was observed in the high-risk ATP III category with 69.4 percent and 58.9 percent during the first and last cycles, respectively," the authors write. Participants with a self-reported history of CHD, angina, heart attack, stroke, and diabetes mellitus or participants with a fasting blood glucose level of 126 mg/dL or greater were placed in the high ATP III risk category.
There were no significant changes observed in the weighted age-standardized screening rates from 1999-2000 to 2005-2006. Among participants with high LDL-C levels, 35.5 percent were unscreened, 24.9 percent undiagnosed, and 39.6 percent untreated or inadequately treated in 2005-2006. In the high-risk category, about one-fifth of participants were eligible for lipid-lowering drug therapy but were not receiving it in 2005-2006.
"Self-reported use of lipid-lowering medications increased from 8.0 percent to 13.4 percent, but screening rates did not change significantly, remaining less than 70 percent during the study periods," the authors note. They add that the goal of improving screening rates may be hindered by the lack of consensus regarding the age at which screening should start.
Editorial: Simplifying the Approach to the Management of Dyslipidemia
In an accompanying editorial, J. Michael Gaziano, M.D., M.P.H., of the VA Boston Healthcare System and Brigham and Women's Hospital, Boston, and Contributing Editor, JAMA; and Thomas A. Gaziano, M.D., M.Sc., of Brigham and Women's Hospital and Harvard School of Public Health, Boston, write that cholesterol guidelines need to be simplified.
"Even though there has been progress in identifying and treating patients with dyslipidemia, the current guidelines are overly complicated, and a simplified risk-based approach is supported by the current data. Abandoning the fixed LDL-C threshold and targets used in many guidelines is justified by the linear relationship of cholesterol lowering and the benefit of the intervention for preventing cardiovascular disease. The use of a simplified risk-based approach could increase the ease of implementation of treatment and increase the number of patients receiving beneficial lipid-lowering therapy."
---------------------------------------------------------------------
Journal References:
1.Elena V. Kuklina; Paula W. Yoon; Nora L. Keenan. Trends in High Levels of Low-Density Lipoprotein Cholesterol in the United States, 1999-2006. JAMA, 2009; 302 (19): 2104-2110
2.J. Michael Gaziano; Thomas A. Gaziano. Simplifying the Approach to the Management of Dyslipidemia. JAMA, 2009; 302 (19): 2148-2149
Biochim Biophys Acta. 2009 Oct 2.
Kappelle PJ, Dallinga-Thie GM, Dullaart RP; for the Diabetes Atorvastatin Lipid Intervention (DALI) study group.
Department of Endocrinology, University Medical Center Groningen, P.O. Box 30001 9700 RB Groningen, The Netherlands.
Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets.
The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein (apo) B. Changes in LDL size and RLP-C were determined in fasting plasma from type 2 diabetic patients after 30 weeks administration of atorvastatin (10 mg daily, n=65; 80 mg daily, n=62) or placebo (n=58). LDL subfraction cholesterol was measured in 74 participants. Atorvastatin lowered LDL cholesterol, non-HDL cholesterol, triglycerides, apo B and RLP-C (P<0.001 for all at each dose) and LDL mean peak particle diameter remained unchanged. Atorvastatin treatment decreased cholesterol concentrations in all LDL subfractions (P<0.001 for each dose). RLP-C at follow-up was lower in those patients achieving the non-HDL cholesterol or the apo B guideline targets (P<0.01), but the LDL cholesterol cut-off value failed to discriminate. In conclusion, atorvastatin lowers fasting RLP-C and LDL subfraction cholesterol in diabetes. The proposed guideline cut-off levels for non-HDL cholesterol and apo B may be superior to the LDL cholesterol target in discriminating between higher and lower RLP-C levels.
Expert Rev Cardiovasc Ther. 2009 Oct;7(10):1231-43.
Paciaroni M, Bogousslavsky J.
Stroke Unit and Division of Cardiovascular Medicine, Universiy of Perugia, Santa Maria della Misericordia Hospital, Sant'Andrea delle Fratte, 06126 - Perugia, Italy.
Statins and stroke prevention.
Over the past decade, statins have been proved to significantly decrease coronary events in the primary and secondary prevention of coronary artery disease. Recent clinical trials have indicated that statins significantly reduce stroke risk in patients with vascular disease. A meta-analysis of randomized trials of statins in combination with other preventive strategies, involving 165,792 individuals, showed that each 1-mmol/l (39 mg/dl) decrease in LDL-cholesterol equates to a reduction in relative risk for stroke of 21.1 (95% CI: 6.3-33.5; p = 0.009). It is not known whether these findings might be due to the cholesterol-reduction effect of statins or to the pleiotropic effects of statins, such as improved endothelial function, decreased platelet aggregability and reduced vascular inflammation. In the secondary prevention of stroke, The Stroke Prevention by Aggressive Reduction of Cholesterol Levels study found that treatment with atorvastatin reduced the risk of recurrent cerebrovascular events in patients with recent stroke or transient ischemic attack but no history of heart disease.
J Clin Hypertens (Greenwich). 2009 Oct;11(10):585-93.
Ferdinand KC, Flack JM, Saunders E, Victor R, Watson K, Kursun A, Jamieson MJ, Shi H.
Association of Black Cardiologists, Atlanta, GA 30349, USA.
Amlodipine/Atorvastatin single-pill therapy for blood pressure and lipid goals in African Americans: influence of the metabolic syndrome and type 2 diabetes mellitus.
African Americans with diabetes +/- the metabolic syndrome are at high risk for cardiovascular disease. This subanalysis of the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points (CAPABLE) trial studied attainment of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) goals by 8 flexibly titrated doses (5/10-10/80 mg) of amlodipine/atorvastatin single pill in 494 African Americans with hypertension and dyslipidemia, according to the presence of diabetes +/- the metabolic syndrome. In 169 diabetic patients, the metabolic syndrome was associated with poorer BP goal attainment (38.5% vs 48.5% in diabetic patients without the metabolic syndrome). Among diabetic patients (+/- the metabolic syndrome) 61% to 62% reached LDL-C goal. More than 60% of patients with diabetes uncontrolled for LDL-C were maintained on suboptimal atorvastatin therapy (mean final dose: 29.9 mg vs maximum of 80 mg). Reluctance to intensify therapy to attain accepted targets in high-risk individuals suggests a degree of clinical inertia not explained by objective evidence of dose-dependent intolerance.
Circ J. 2009 Oct 13.
Ji Q, Mei Y, Wang X, Sun Y, Feng J, Cai J, Xie S, Chi L.
Department of Thoracic Cardiovascular Surgery, Tongji Hospital, Tongji University.
Effect of Preoperative Atorvastatin Therapy on Atrial Fibrillation Following Off-Pump Coronary Artery Bypass Grafting.
Background: Atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is still the most common postoperative arrhythmic complication. Previous studies report that patients undergoing preoperative statin therapy had a lower incidence of postoperative AF. This study aimed to assess the effect of preoperative atorvastatin therapy on preventing AF following off-pump CABG in a randomized, controlled trial. Methods and Results: The 140 consecutive patients undergoing elective off-pump CABG, without a history of AF or previous statin treatment, were enrolled and randomly assigned to a statin (atorvastatin 20 mg/day, n=71) or a control group (placebo, n=69) starting 7 days preoperatively. The primary endpoint was the occurrence of postoperative AF; secondary endpoints were major adverse in-hospital cardiac and cerebrovascular events and identification of variables predicting postoperative AF. Atorvastatin significantly reduced the incidence of postoperative AF and the postoperative peak C-reactive protein (CRP) level vs placebo (14% vs 34%, P=0.009; 126.5 +/-22.3 vs 145.2 +/-31.6 mg/L, P<0.0001). Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF (odds ratio (OR) 0.219, P=0.005), whereas a high postoperative CRP level was associated with increased risk (OR 2.011, P=0.013). Conclusions: Administration of atorvastatin 20 mg/day, initiated 1 week before elective off-pump CABG and continued in the postoperative period, significantly decreases postoperative AF.
Perfusion. 2009 Oct 20.
Kurban S, Mehmetoglu I, Ege E.
Department of Biochemistry, Meram Faculty of Medicine, University of Selcuk, Konya, Turkey.
Effect of preoperative atorvastatin therapy on paraoxonase activity and oxidative stress after coronary artery bypass grafting.
The aim of this study was to examine the influence of preoperative atorvastatin therapy on oxidative stress in coronary artery bypass grafting (CABG) patients. Forty patients who underwent elective CABG were enrolled into the study. Of these patients, 20 received atorvastatin (Group I) for 15 days prior to surgery and 20 patients did not use any antihyperlipidemic agents preoperatively (Group II). Serum paraoxonase 1 (PON1) and arylesterase activities, and total antioxidant status (TAS) and total oxidant status (TOS) were measured before surgery and at 1, 6 and 24 hours after the operation. Paraoxonase 1 and arylesterase activities (p<0.001) and TAS levels (p<0.001 for 1(st) hour and p<0.05 for 6(th) hour) in Group II were significantly reduced at the 1(st) and 6(th) hours after the operation, whereas the activities of the enzymes (p<0.01) and TAS levels (p<0.05) were significantly reduced only at the 1(st) hour after the operation in Group I. The total oxidant status of both groups was significantly increased at the 1(st) hour after operation (p<0.05 for Group I and p<0.01 for Group II). In conclusion, 15 days of preoperative atorvastatin therapy does not significantly change either the serum PON1 activity or the oxidative stress after CABG.
Int J Impot Res. 2009 Oct 29.
Dadkhah F, Safarinejad MR, Asgari MA, Hosseini SY, Lashay A, Amini E.
Department of Urology, Shahid Modarress Hospital, Shahid Beheshti University (MC), Tehran, Iran.
Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil.
Despite the initial enthusiasm, the significant number of patients in whom sildenafil is contraindicated or ineffective is a major challenge to all urologists. Our aim was to determine the safety and efficacy of adjunctive atorvastatin in restoring normal erectile function in hypercholesterolemic (low-density lipoprotein (LDL) cholesterol >120 mg per 100 ml) sildenafil nonresponders. The study comprised 131 men with ED not responding to sildenafil citrate. They were randomized either to 40 mg atorvastatin daily (n=66, group 1) or matching placebo (n=65, group 2) for 12 weeks while they were taking on-demand 100 mg sildenafil. Erectile function was subjectively assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire and response to the global efficacy question (GEQ). Serum biochemical and lipid profile (total cholesterol, triglycerides, LDL cholesterol and high-density lipoprotein cholesterol) analyses were performed at baseline and repeated at post-treatment weeks 6 and 12. Compared with the placebo group (59 patients, mean age+/-s.d. 61.9+/-6.1, mean years ED 3.9+/-1.8), the atorvastatin group (59 patients, mean age+/-s.d. 63.9+/-6.9, mean years ED 3.7+/-1.6) had significantly greater improvements in all IIEF-5 questions (P=0.01) and GEQ (P=0.001). Subgroup analyses did reveal trends in the atorvastatin group to indicate that a change in the IIEF-5 score is affected by age, severity of ED and baseline serum levels of LDL. Patients with moderate (r=0.28, P=0.01) and severe (r=0.20, P=0.01) ED had better positive response rates to adjunctive atorvastatin than patients with mild to moderate ED. None of the patients taking atorvastatin achieved a response of 5 to the IIEF-5 questions and none of the patients regained normal erectile function as defined by the IIEF-5 score >21. Subjects experienced a statistically significant but modest improvement in erectile function. Further investigation is needed to test the usefulness of long-term atorvastatin administration to restore erectile function in sildenafil nonresponders.
Pharmazie. 2006 Sep;61(9):805-6.
Mendoza L, Hajduch M, Plausinaitis R, Platilova V, Emritte N, Svoboda M.
IQA, as, Prague, Czech Republic.
Pharmacokinetic and bioequivalence testing of atorvastatin formulations in healthy male volunteers.
The present study is to compare the bioavailability of two atorvastatin formulations in 52 healthy volunteers. This study reached the conclusion that concluded that the atorvastatin formulation elaborated by Drogsan Pharmaceuticals, was bioequivalent to the Lipitor in its rate and extent of absorption.
The aim of this study was to compare the bioavailability of two atorvastatin formulations (Divator Drogsan Pharmaceuticals, Ankara, Turkey, as the test formulation, and Lipitor, Pfizer Ireland Pharmaceuticals, Dublin, Ireland, as the reference formulation) in 52 healthy volunteers. The study was conducted using a randomised, single-dose, two-way crossover study with a 2-week washout period between the doses. Since the 90% confidence intervals for Cmax, AUC0-72 and AUC0-proprtional to ratios for both, the parent atorvastatin and its main active metabolite ortho-hydroxy atorvastatin, were within the pre-defined Bioequivalance acceptance limits approved by EMEA, we concluded that the atorvastatin formulation elaborated by Drogsan Pharmaceuticals, was bioequivalent to the Lipitor in its rate and extent of absorption.
J Am Coll Cardiol. 2005 Mar 1;45(5):733-42.
Yonemura A, Momiyama Y, Fayad ZA, Ayaori M, Ohmori R, Higashi K, Kihara T, Sawada S, Iwamoto N, Ogura M, Taniguchi H, Kusuhara M, Nagata M, Nakamura H, Tamai S, Ohsuzu F.
National Defense Medical College, Saitama, Japan.
Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging.
The given experiment was done to elucidate the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques. The study concluded that one-year 20-mg atorvastatin treatment induced regression of thoracic aortic plaques with marked LDL cholesterol reduction, whereas it resulted in only retardation of plaque progression in abdominal aorta. It is clear that thoracic and abdominal aortic plaques may have different susceptibilities to lipid lowering.
OBJECTIVES: We sought to elucidate the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques. BACKGROUND: Regression of thoracic aortic plaques by simvastatin was demonstrated using magnetic resonance imaging (MRI). However, the effects of different doses of statin have not been assessed. METHODS: Using MRI, we investigated the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques in 40 hypercholesterolemic patients who were randomized to receive either dose. Treatment effects were evaluated as changes in vessel wall thickness (VWT) and vessel wall area (VWA) of atherosclerotic lesions from baseline to 12 months of treatment. RESULTS: The 20-mg dose induced a greater low-density lipoprotein (LDL) cholesterol reduction than did the 5-mg dose (-47% vs. -34%, p < 0.001). Although 20 mg and 5 mg reduced C-reactive protein (CRP) levels (-47% and -28%), the degree of CRP reduction did not differ between the two doses. The 20-mg dose reduced VWT and VWA of thoracic aortic plaques (-12% and -18%, p < 0.001), whereas 5 mg did not (+1% and +4%). Regarding abdominal aortic plaques, even 20 mg could not reduce VWT or VWA (-1% and +3%), but instead progression was observed with 5-mg treatment (+5% and +12%, p < 0.01). Notably, the degree of plaque regression in thoracic aorta correlated with LDL cholesterol (r = 0.64) and CRP (r = 0.49) reductions. Although changes in abdominal aortic plaques only weakly correlated with LDL cholesterol reduction (r = 0.34), they correlated with age (r = 0.41). CONCLUSIONS: One-year 20-mg atorvastatin treatment induced regression of thoracic aortic plaques with marked LDL cholesterol reduction, whereas it resulted in only retardation of plaque progression in abdominal aorta. Thoracic and abdominal aortic plaques may have different susceptibilities to lipid lowering.
Br J Ophthalmol. 2005 Mar;89(3):275-9.
Thomas PB, Albini T, Giri RK, See RF, Evans M, Rao NA.
Doheny Eye Institute, DVRC 211, 1450 San Pablo Street, Los Angeles CA 90033, USA.
The effects of atorvastatin in experimental autoimmune uveitis.
From the given study it is clear that atorvastatin treatment had no effect on Th1 and Th2 cytokine transcription against experimental autoimmune uveitis (EAU). Although histological grading suggested mildly decreased inflammation in the high dose treated group, the equivalence of cytokine expression in all groups suggests that the statins may not modulate IRBP induced uveoretinitis.
AIM: To investigate the effect of atorvastatin (Lipitor), a commonly used drug for dyslipidaemia in experimental autoimmune uveitis (EAU). METHODS: 48 B10-RIII mice were immunised with human interphotoreceptor retinoid binding protein (IRBP) peptide p161-180. They were divided into three groups of 16 each and treated orally once daily for 14 days; group one received phosphate buffered saline (control group), group two received 1 mg/kg of atorvastatin (low dose group), and group three received 10 mg/kg (high dose). On day 14 lymph nodes, spleens, and right eyes were harvested. RNA was extracted from lymph nodes for RNase protection assay (RPA) to determine proinflammatory (IL-1alpha and IL-1beta), Th1 (TNF-alpha, IL-2, IL-12), and Th2 (IL-4, IL-5, and IL-10) cytokine levels. Protein was extracted from spleens for western blot to detect the expression of phosphorylated signal transducer and activator of transcription (STAT) 4 and STAT6. The severity of inflammation in enucleated eyes was graded by a masked observer. Paired t test was performed for the mean difference in histological scoring between treated groups and the immunised control group. RESULTS: Surprisingly, atorvastatin did not modulate the immune response. The proinflammatory cytokines, IL-1alpha and IL-1beta, and Th1 cytokines, TNF-alpha and IL-2, were upregulated equally in control and atorvastatin treated groups. IL-12 and Th2 cytokines were not upregulated in all three groups. Western blot analysis showed high levels of phosphorylated STAT4, but not STAT6 protein in the control and atorvastatin treated groups. Mean differences in histological scoring between treated groups and the immunised control group were not statistically significant. CONCLUSIONS: Atorvastatin treatment had no effect on Th1 and Th2 cytokine transcription. Although histological grading suggested mildly decreased inflammation in the high dose treated group, the equivalence of cytokine expression in all groups suggests that the statins may not modulate IRBP induced uveoretinitis.
Lipitor description...
|
|
Drug category:Antilipemic agents
 Lipitor scientific update
Buy here
|
|
My Basket