MedWorm: Pravastatin

No significant effect of uridine or pravastatin treatment for HIV lipoatrophy in men who have ceased thymidine analogue nucleoside reverse transcriptase inhibitor therapy: a randomized trial*

HIV Medicine — Mon, 08 Mar 2010 00:00:00 +0100

Lipoatrophy can complicate thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI)-based antiretroviral therapy (ART). Lipoatrophy may be less likely with ART including ritonavir-boosted lopinavir (LPV/r). Small, placebo-controlled studies found that uridine (in tNRTI recipients) and pravastatin improved HIV lipoatrophy over 12 weeks. Today, most patients with lipoatrophy receive non-tNRTI-based ART; the effect of uridine in such patients is unknown. We performed a prospective, randomized trial in lipoatrophic adults with plasma HIV RNA (Source: HIV Medicine)

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TRAF1/C5 polymorphism is not associated with increased mortality in rheumatoid arthritis; two large longitudinal studies

Arthritis Research and Therapy — Fri, 05 Mar 2010 00:00:00 +0100

Conclusions: The TRAF1/C5 region is not associated with an increased mortality risk. (Source: Arthritis Research and Therapy)

Pravastatin/simvastatin: Skin disorders: 20 case reports

Reactions — Mon, 01 Mar 2010 14:50:10 +0100

(Source: Reactions)

PRAVASTATIN SODIUMtablet [International Labs, Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Thu, 25 Feb 2010 05:00:00 +0100

Updated Date: Feb 25, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Pitavastatin: A New HMG-CoA Reductase Inhibitor(March) (CE).

The Annals of Pharmacotherapy — Tue, 23 Feb 2010 00:00:00 +0100

CONCLUSIONS: In light of the lack of outcome data, pitavastatin offers no clear advantage over other drugs in this class. PMID: 20179258 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

Statins potently reduce the cytokine-mediated IL-6 release in SMC / MNC cocultures.

J Cell Mol Med — Tue, 16 Feb 2010 00:00:00 +0100

Authors: Loppnow H, Zhang L, Buerke M, Lautenschläger M, Chen L, Frister A, Schlitt A, Luther T, Song N, Hofmann B, Rose-John S, Silber RE, Müller-Werdan U, Werdan K Inflammatory pathways are involved in the developement of atherosclerosis. Interaction of vessel wall cells and invading monocytes by cytokines may trigger local inflammatory processes. HMG-CoA reductase inhibitors (statins) are a standard medication used in cardiovascular diseases. They are thought to have anti-inflammatory capacities, in addition to their lipid-lowering effects. We investigated the anti-inflammatory effect of statins in the cytokine-mediated-interaction-model of human vascular smooth muscle cells (SMC) and human mononuclear cells (MNC). In this atherosclerosis-related inflammatory model LPS (li...

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Mitochondrial KATP channels-derived reactive oxygen species activate pro-survival pathway in pravastatin-induced cardioprotection

Apoptosis — Fri, 12 Feb 2010 07:14:19 +0100

Abstract Reactive oxygen species (ROS) are important intracellular signaling molecules and are implicated in cardioprotective pathways including ischemic preconditioning. Statins have been shown to have cardioprotective effects against ischemia/reperfusion injury, however, the precise mechanisms remain to be elucidated. We hypothesized that ROS-mediated signaling cascade may be involved in pravastatin-induced cardioprotection. Cultured rat cardiomyocytes were exposed to H2O2 for 30 min to induce cell injury. Pravastatin significantly suppressed H2O2-induced cell death evaluated by propidium iodide staining and the MTT assay. Incubation with pravastatin activated catalase, and prevented a ROS burst induced by H2O2, which preserved mitochondrial membrane potential. Protec...

PRAVASTATIN SODIUMtablet [Cobalt Laboratories Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 12 Feb 2010 05:00:00 +0100

Updated Date: Feb 12, 2010 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Lithium/olanzapine/pravastatin interaction: Exanthema: case report

Reactions — Wed, 10 Feb 2010 14:08:42 +0100

(Source: Reactions)

HMGCR gene polymorphism is associated with stroke risk in the EPIC-Norfolk study

European Journal of Cardiovascular Prevention and Rehabilitation — Mon, 01 Feb 2010 00:00:00 +0100

Conclusion: An association between the rs17238540 SNP and stroke risk was observed, independent of the effect of the SNP on the blood pressure. The possible mechanisms involved, besides the effect on blood pressure, might be related to pleiotropic functions of the HMGCR, and remain to be explored. (Source: European Journal of Cardiovascular Prevention and Rehabilitation)

Effect of olmesartan and pravastatin on experimental cerebral aneurysms in rats.

Brain Research — Tue, 26 Jan 2010 00:00:00 +0100

Authors: Kimura N, Shimizu H, Eldawoody H, Nakayama T, Saito A, Tominaga T, Takahashi A The major initiation process of intracranial aneurysms is thought to involve endothelial dysfunction due to hemodynamic stress. Angiotensin II type 1 receptor blockers and statins improve vascular endothelium function. The effects of olmesartan and pravastatin were investigated on the development of experimental aneurysms in rats. Eighty-three rats underwent aneurysm induction. Seven groups of 10-14 rats were treated with low or high dose olmesartan, low or high dose pravastatin, low doses of olmesartan and pravastatin, hydralazine, or no drug (control) for 12weeks, when rats were sacrificed for vascular corrosion casting and scanning electron microscopy. Aneurysmal changes at the anterior cerebral-...

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Fibrate/Statin Initiation in Warfarin Users and Gastrointestinal Bleeding Risk

The American Journal of Medicine — Sun, 24 Jan 2010 14:28:51 +0100

Conclusions: Initiation of a fibrate or statin that inhibits CYP3A4 enzymes, including atorvastatin, was associated with an increased risk of hospitalization for gastrointestinal bleeding. Initiation of pravastatin, which is mainly excreted unchanged, was not associated with an increased risk. (Source: The American Journal of Medicine)

Red Yeast Rice Comparable to Pravastatin for Statin-Intolerant Patients

Medscape Today Headlines — Fri, 22 Jan 2010 16:10:00 +0100

Red-yeast-rice and pravastatin treatment arms both had low withdrawal rates and achieved comparable reductions in LDL-cholesterol levels, report researchers. Heartwire (Source: Medscape Today Headlines)

Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3

British Journal of Pharmacology — Fri, 22 Jan 2010 00:00:00 +0100

Conclusions and implications: We demonstrated that the conserved positively charged amino acids Lys41 and Arg580 are pivotal to the transport activity of OATP1B3. (Source: British Journal of Pharmacology)

Red yeast rice comparable to pravastatin for statin-intolerant patients

theHeart.org — Thu, 21 Jan 2010 20:00:04 +0100

Red-yeast-rice and pravastatin treatment arms both had low withdrawal rates and achieved comparable reductions in LDL-cholesterol levels, report researchers. For complete story visit theheart.org. (Source: theHeart.org)

Endothelial Function Impairment in Chronic Venous Insufficiency: Effect of Some Cardiovascular Protectant Agents

Angiology — Thu, 21 Jan 2010 06:43:06 +0100

In segments of human varicose veins, endothelial function was assessed by measuring relaxation induced by acetylcholine in noradrenaline-precontracted preparations. In addition, concentration-response curves to acetylcholine were obtained before and after incubation with the arterial endothelium protectant agents captopril, losartan, troglitazone, pravastatin, or simvastatin. The antivaricose agent escin was also tested. Mean acetylcholine-induced relaxation of varicose venous rings was about 13%, approximately one third of that reported for control saphenous veins. Concentration-response curves to acetylcholine were ‘‘u’’ shaped, the result of endothelium-mediated relaxation at low concentrations, superseded by subsequent smooth muscle contractile responses. Relaxa...

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Study Finds Red Yeast Rice Efficacy Comparable to Statin

Modern Medicine — Thu, 21 Jan 2010 00:00:00 +0100

The alternative therapy red yeast rice performes comparably to the lipid-lowering drug pravastatin in reducing low-density lipoprotein cholesterol levels in patients who had previously had to discontinue statin therapy because of muscle pain, according to a study in the Jan. 15 issue of the American Journal of Cardiology. (Source: Modern Medicine)

Variation in the CBP gene involved in epigenetic control associates with cognitive function.

Neurobiology of Aging — Thu, 21 Jan 2010 00:00:00 +0100

Authors: Trompet S, Craen AJ, Jukema JW, Pons D, Slagboom PE, Kremer D, Bollen EL, Westendorp RG Research into the pathologic mechanisms of neurodegenerative diseases has revealed that CREB binding protein (CBP) plays an important role in cognitive dysfunction. Loss of one copy of this gene leads to a syndrome with severe cognitive dysfunction. We investigated the association between four common variants in the CBP gene and cognitive function in 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Baseline associations between genetic variation and cognitive function were assessed with linear regression. Longitudinal associations were assessed with linear mixed models. All analyses were adjusted for sex, age, education, country, version of test, a...

Beneficial microvascular and anti-inflammatory effects of pravastatin during sepsis involve nitric oxide synthase III

British Journal of Anaesthesia — Tue, 19 Jan 2010 16:34:57 +0100

Conclusions Pravastatin improved NOS III-mediated vessel relaxation and exerted anti-inflammatory effects within the microcirculation after LPS administration in rats. Pravastatin therefore appears to have beneficial effects during sepsis, as a result of increased microvascular expression and function of NOS III. (Source: British Journal of Anaesthesia)

Do statins improve outcomes and reduce the incidence of vasospasm after aneurysmal subarachnoid hemorrhage: a meta-analysis

NeLM - Cerebrovascular Disorders — Mon, 18 Jan 2010 00:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This review evaluated the effectiveness statins in preventing cerebral vasospasm in patients who have had aneurysmal subarachnoid haemorrhage (SAH). The evidence suggested that statins may be promising, but the authors' conclusions appear over-optimistic given the limited evidence available. [Two studies used 80 mg simvastatin daily. One study used 40 mg pravastatin daily.] CRD Commentary: This review addressed a clear question supported by appropriate inclusion criteria. A number of relevant electronic databases were searched without language restrictions. Efforts were made to retrieve unpublished data. Suitable methods were used throughout the review process to minimise the risks of reviewer error and bias. In terms ...

Myelin Basic Protein Priming Reduces the Expression of Foxp3 in T Cells via Nitric Oxide.

Journal of Immunology — Mon, 18 Jan 2010 00:00:00 +0100

Authors: Brahmachari S, Pahan K Regulatory T cells (Tregs) play a vital role in autoimmune disorders. Among several markers, forkhead box p3 (Foxp3) is the most specific with regard to Treg activity. Therefore, understanding mechanisms that regulate Foxp3 expression is a critical step for unraveling the complicacy of autoimmune pathophysiology. The present study was undertaken to investigate the crosstalk between NO and Tregs. Interestingly, after myelin basic protein (MBP) priming, the expression of Foxp3 decreased in MBP-primed T cells. However, blocking NO either by inhibiting inducible NO synthase with l-N(6)-(1-iminoethyl)-lysine hydrochloride or through scavenging with PTIO or by pharmacological drugs, such as pravastatin, sodium benzoate, or gemfibrozil, restored the expression ...

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Endothelial function in subjects with isolated low HDL cholesterol: role of nitric oxide and circulating progenitor cells

AJP: Endocrinology and Metabolism — Fri, 15 Jan 2010 01:51:49 +0100

Epidemiologic studies have shown that a low level of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular diseases. The purpose of this study was to determine the contribution of isolated low HDL cholesterol to endothelial function. Thirty-nine subjects with low HDL cholesterol who had no other cardiovascular risk factors were selected from the 5,417 participants from our population. We evaluated flow-mediated vasodilation (FMD) before and after 4 wk of treatment with the HMG-CoA reductase inhibitor pravastatin in 29 of the 39 subjects with isolated low HDL cholesterol. FMD was lower in the low-HDL-cholesterol group (n = 29) than in the control group (n = 29), whereas NTG-induced vasodilation was similar in the two groups. Pravastatin increased HDL cholesterol, ur...

Reply

Journal of the American College of Cardiology — Thu, 14 Jan 2010 13:52:19 +0100

First, we express our deep appreciation for the sincere criticism by Dr. Kaneda and colleagues of our paper (). However, we have a few concerns regarding their arguments. The REVERSAL (REVERSing Atherosclerosis with Aggressive Lipid Lowering) study () examined patients with stable coronary artery disease who could undergo an elective cardiac catheterization, whereas the PROVE-IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) () and our JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) study examined patients with acute coronary syndrome. Several reports have been published that nonculprit plaque differs in tissue characteristics between acute coronary syndrome and stable coronary ar...

Low-dosage statins reduce choroidal damage in hypercholesterolemic rabbits

Acta Ophthalmologica — Fri, 08 Jan 2010 00:00:00 +0100

Conclusion: Treatment with a low dosage of fluvastatin sodium or pravastatin sodium reduced the lipid build-up as well as the macrophages in the choroid and restored the vascular lumens of choroidal vessels independently of the cholesterol effect. The normal ultrastructural features of choroidal EC and VSMC in statin-treated animals suggest that the endothelial function is preserved and the ischaemia reduced. (Source: Acta Ophthalmologica)

Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice.

Experimental and Toxicologic Pathology — Thu, 07 Jan 2010 00:00:00 +0100

This study investigated the protective effects of pravastatin against cisplatin-induced nephrotoxicity and the possible mechanisms in mice. Pravastatin showed significant protection as evidenced by the decrease of elevated serum creatinine (CRE) and blood urea nitrogen (BUN), and improvement of histopathological injury induced by cisplatin. The formation of kidney malondialdehyde (MDA) with a concomitant reduction of reduced glutathione (GSH) were inhibited by pravastatin, while the activities of kidney superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) were increased. The over expressions of kidney induced nitric oxide synthase (iNOS) and nitrotyrosine (3-NT) were suppressed by pravastatin. Pravastatin suppressed cisplatin-induced p38 mitogen-activated protein ...

Coronary Heart Disease in Moderately Hypercholesterolemic, Hypertensive Black and Non-Black Patients Randomized to Pravastatin Versus Usual Care

Medscape Today Headlines — Wed, 06 Jan 2010 11:10:04 +0100

Coronary heart disease endpoints are examined in relation to race and Pravastatin use. Does Pravastatin prevent CHD in blacks? American Heart Journal (Source: Medscape Today Headlines)

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Relation of Change in Apolipoprotein B/Apolipoprotein A-I Ratio to Coronary Plaque Regression After Pravastatin Treatment in Patients With Coronary Artery Disease

The American Journal of Cardiology — Tue, 05 Jan 2010 13:52:33 +0100

Some investigations have looked into the ability of measurements of apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio to predict cardiovascular events. We hypothesized that a decrease in the apoB/apoA-1 ratio by statin therapy would act on suppression of coronary plaque progression. A 6-month prospective study was conducted of 64 patients with coronary artery disease treated with pravastatin. The plaque volume, assessed by volumetric intravascular ultrasonography, had decreased significantly by 12.6% (p (Source: The American Journal of Cardiology)

Pravastatin Protects Against Heart Disease in Blacks

Medscape Today Headlines — Mon, 04 Jan 2010 17:08:46 +0100

The cholesterol-lowering drug pravastatin prevents coronary heart disease in blacks, according to trial results published in the December American Heart Journal. Reuters Health Information (Source: Medscape Today Headlines)

The disposition of pravastatin in a rat model of streptozotocin-induced diabetes and organic anion transporting polypeptide 2 and multidrug resistance-associated protein 2 expression in the liver.

Biological and Pharmaceutical Bulletin — Fri, 01 Jan 2010 00:00:00 +0100

Authors: Hasegawa Y, Kishimoto S, Shibatani N, Inotsume N, Takeuchi Y, Fukushima S The combination of diabetes and hyperlipidemia promotes the development of atherosclerosis. Therefore, it is important for diabetic patients to control blood fat. 3-Hydroxy-3-methylglutaryl enzyme A (HMG-CoA) reductase inhibitors (statins), like pravastatin, are frequently administered to diabetic patients for this purpose. Although the alterations of metabolic enzymes and transporters in the diabetic liver maybe change the disposition of pravastatin, the effect has not been fully investigated. In the present study, we investigated the disposition of pravastatin and the mRNA expression of transporters in the liver. Pravastatin (5 mg.kg(-1) body weight) was administered intravenously to diabetic rats, and...

In vitro antioxidant activity of pravastatin provides vascular protection.

European Journal of Pharmacology — Tue, 29 Dec 2009 00:00:00 +0100

In conclusion, this study can contribute to elucidate the mechanism responsible for the antioxidant activity of pravastatin, and describes relationship between a scavenger effect of pravastatin and the improvement of vascular reactivity. PMID: 20044990 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)

Treatment of symptomatic HyperLp(a)lipoproteinemia with LDL-apheresis: a multicentre study.

Atherosclerosis. Supplements. — Tue, 29 Dec 2009 00:00:00 +0100

Authors: Stefanutti C, D'Alessandri G, Russi G, De Silvestro G, Zenti MG, Marson P, Belotherkovsky D, Vivenzio A, Di Giacomo S LDL-apheresis (LDLa) efficacy in the treatment of symptomatic HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial. After 3.1+/-2.7 years of weekly and biweekly treatment, the data from 19 patients (males:12; females:7; aged 53.8+/-9.3 years; mean body mass index: 24.6+/-2.3 Kg/m(2)) were evaluated. Data were collected using the same questionnaire shared by 5 participating centres. A total of 2331 procedures were performed. A mean of 3593.7+/-800.3 ml of plasma or 8115.3+/-2150.1 ml of blood, depending upon the technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was regularly treated on average every 10.1+/-2.6 days. ...

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Effects of Pravastatin on Serum Osteoprotegerin Levels in Patients With Hypercholesterolemia and Type 2 Diabetes

Angiology — Thu, 24 Dec 2009 06:50:17 +0100

In this study, we examined whether treatment with pravastatin can alter osteoprotegerin levels in patients with hypercholesterolemia and type 2 diabetes. Osteoprotegerin levels were significantly increased from 6.64 ± 2.18 pmol/L at baseline to 7.08 ± 2.29 pmol/L (P = .024) after 3-month treatment with pravastatin. These increases in osteoprotegerin levels remained after 6 months of treatment (7.05 ± 2.22 pmol/L, P = .026). These findings suggest that pravastatin may exert its pleiotropic effects in part through alteration of osteoprotegerin levels. (Source: Angiology)

Synergistic antifibrotic efficacy of statin and protein kinase C inhibitor in hepatic fibrosis

AJP: Gastrointestinal and Liver Physiology — Sat, 19 Dec 2009 00:12:02 +0100

In conclusion, simultaneous treatment with statin and PKC inhibitor synergistically enhanced the antifibrotic efficacy in both in vitro and in vivo models of hepatic fibrosis and may therefore have therapeutic implication for reducing hepatic fibrosis. (Source: AJP: Gastrointestinal and Liver Physiology)

Pravastatin treatment causes a shift in the balance of hippocampal neurotransmitter binding densities towards inhibition.

Brain Research — Fri, 18 Dec 2009 00:00:00 +0100

Authors: Müller HD, Berger C, Schwab S, Sommer C Since pravastatin, a HMG-CoA reductase inhibitor, has recently been shown to reduce infarct volumes and glutamate release in a rat model of ischemic stroke, the aim of the present study was to investigate whether this neuroprotective effect may be due to a modulation of excitatory and inhibitory neurotransmitter receptors. Therefore, Wistar rats were treated six times in 4 days with pravastatin or saline and allowed to survive for 6 hours or 5 days (n = 10 per time point and group), respectively. Using quantitative receptor autoradiography, ligand binding densities of [(3)H]MK-801, [(3)H]AMPA, and [(3)H]muscimol for labeling of NMDA, AMPA, and GABA(A) receptors were analyzed in sensorimotor cortices Par1 and Par2, the striatum, and ...

Commentary to factors predicting cardiovascular events in statin-treated diabetic and non-diabetic patients with coronary atherosclerosis (1)

Atherosclerosis — Fri, 18 Dec 2009 00:00:00 +0100

In this study HDL cholesterol levels were predictive of major cardiovascular events even among patients with LDL cholesterol levels below 1.8mmol/l. (Source: Atherosclerosis)

Rosuvastatin Better Than Pravastatin for Protease-Inhibitor-Related Dyslipidemia

Medscape Today Headlines — Thu, 17 Dec 2009 17:46:37 +0100

Rosuvastatin is better than pravastatin at lowering levels of LDL cholesterol and triglycerides in HIV-infected patients with protease-inhibitor (PI)-associated dyslipidemia, according to an article in the January 2nd issue of AIDS. Reuters Health Information (Source: Medscape Today Headlines)

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Rosuvastatin more effective than pravastatin in HIV-1-infected patients receiving a boosted protease inhibitor

NeLM - Cardiovascular Medicine — Thu, 17 Dec 2009 00:00:00 +0100

Source: Reuters Health News Area: News According to a randomised controlled study published in the journal AIDS, rosuvastatin 10 mg/day is more effective than pravastatin 40 mg/day at lowering levels of LDL cholesterol and triglycerides in HIV-1-infected patients receiving a boosted protease inhibitor (PI). It is well documented that HIV infection and its treatment with PIs, especially when boosted with ritonavir, can cause dyslipidaemia, and with the exception of fluvastatin, pravastatin and rosuvastatin, all statins interact with PI metabolism via CYP450. In these patients, pravastatin is recommended for patients with PI-associated dyslipidaemia. In this randomised controlled trial, researchers randomised 88 HIV-1-infected patients treated with boosted ritonavir, t...

Effect of long- and short-term treatments with pravastatin on diabetes mellitus and pancreatic fibrosis in the Otsuka–Long–Evans–Tokushima Fatty rat

British Journal of Pharmacology — Wed, 16 Dec 2009 00:00:00 +0100

Conclusions and implications: The results suggest that long-term treatment with pravastatin improves DM and pancreatic fibrosis via anti-oxidative and anti-fibrotic properties, whereas cessation of pravastatin abolishes these beneficial effects, and accelerates DM and pancreatic fibrosis. (Source: British Journal of Pharmacology)

Pravastatin: Skin ulcers and myopathy in an elderly patient

Reactions — Tue, 15 Dec 2009 14:08:48 +0100

(Source: Reactions)

PRAVASTATIN SODIUMtablet [Mylan Pharmaceuticals Inc.]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Tue, 15 Dec 2009 05:00:00 +0100

Updated Date: Dec 15, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

Reduction in Recurrent Cardiovascular Events With Intensive Lipid-Lowering Statin Therapy Compared With Moderate Lipid-Lowering Statin Therapy After Acute Coronary Syndromes: From the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) Trial

Journal of the American College of Cardiology — Tue, 15 Dec 2009 00:00:00 +0100

Conclusions: Although analytic techniques commonly used in clinical outcomes trials censor patients who experience a component of the primary composite end point, total cardiovascular events are important to patients, clinicians, and health care payers. Maintaining low levels of low-density lipoprotein cholesterol is central to preventing additional atherosclerotic development and subsequent cardiovascular events. Atorvastatin 80 mg, a more intensive low-density lipoprotein cholesterol lowering agent, reduced both first and subsequent primary end point events compared with pravastatin 40 mg after ACS. (Source: Journal of the American College of Cardiology)

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Cardiovascular Outcomes in Randomized Trials: Should Time to First Event for “Hard” End Points Remain the Standard Approach?⁎

Journal of the American College of Cardiology — Tue, 15 Dec 2009 00:00:00 +0100

This issue of the Journal contains 2 papers that provide interesting insights from 2 large randomized lipid-lowering trials that addressed relatively similar scientific questions. In the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) trial, investigators compared atorvastatin (80 mg) with pravastatin (40 mg) for patients randomly assigned to treatment after an acute coronary syndrome (ACS) (). In the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial (), the 80-mg dosage of atorvastatin was compared with 20 to 40 mg of simvastatin in patients with a prior myocardial infarction (MI). Both studies were performed well and contributed significantly to the contemporary understanding of ...

Journal Scan: Reduction in Recurrent Cardiovascular Events With Intensive Lipid-Lowering Statin Therapy Compared With Moderate Lipid-Lowering Statin Therapy After Acute Coronary Syndromes: From the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Trial (J Am Coll Cardiol 2009;54:2358-2362.)

Cardiosource — Sat, 12 Dec 2009 08:49:03 +0100

This is a post-hoc analysis of the PROVE IT-TIMI 22 trial. Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between high-dose atorvastatin and pravastatin in the PROVE IT-TIMI 22 trial. (Source: Cardiosource)

Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial [Patient-Oriented and Epidemiological Research]

The Journal of Lipid Research — Fri, 11 Dec 2009 22:48:35 +0100

Cholesterol homeostasis, defined as the balance between absorption and synthesis, influences circulating cholesterol concentrations and subsequent coronary heart disease (CHD) risk. Statin therapy targets the rate-limiting enzyme in cholesterol biosynthesis and is efficacious in lowering CHD events and mortality. Nonetheless, CHD events still occur in some treated patients. To address differences in outcome during pravastatin therapy (40 mg/day), plasma markers of cholesterol synthesis (desmosterol, lathosterol) and fractional cholesterol absorption (campesterol, sitosterol) were measured, baseline and on treatment, in the Prospective Study of Pravastatin in the Elderly at Risk trial participants with (cases, n = 223) and without (controls, n = 257) a CHD event. Pravastatin therapy decreas...

The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials

NeLM - Cerebrovascular Disorders — Fri, 11 Dec 2009 00:00:00 +0100

Source: DARE Area: Evidence > Disease Focused Reviews CRD Summary: This generally well-conducted review concluded that statin use in patients without established cardiovascular disease, but with cardiovascular risk factors, was associated with significantly improved survival and large reductions in the risk of major cardiovascular events. This conclusion reflected the results of an appropriate synthesis of large, high-quality trials and is likely to be reliable. [Included studies used pravastatin, lovastatin, atorvastatin, simvastatin or rosuvastatin.] CRD Commentary: The review question was clear and supported by specific inclusion criteria. The authors searched several relevant databases and this reduced their chances of omitting relevant studies. No systematic attempts to locate un...

Statin response enhanced in Black CHD patients

MedWire News - Lipidology — Thu, 10 Dec 2009 00:00:00 +0100

Researchers have confirmed a significant reduction in coronary events among Black patients who received pravastatin in ALLHAT-LLT, despite the overall negative results of the study. (Source: MedWire News - Lipidology)

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High Innate Production Capacity of Proinflammatory Cytokines Increases Risk for Death from Cancer: Results of the PROSPER Study.

Clinical Cancer Research — Tue, 08 Dec 2009 00:00:00 +0100

CONCLUSIONS: High innate production capacity of proinflammatory cytokines is associated with an increased risk for death from cancer, probably because of increased tumor growth and metastasis. Because there was no association between innate production capacity and cancer incidence, the association between circulating levels and cancer incidence at least partially reflects reversed causality. (Clin Cancer Res 2009;15(24):7744-8). PMID: 19996221 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Effect of Intensive Statin Therapy on Clinical Outcomes Among Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome: PCI-PROVE IT: A PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) Substudy

Journal of the American College of Cardiology — Sat, 05 Dec 2009 13:48:57 +0100

Conclusions: Among patients with ACS who undergo PCI, intensive statin therapy reduces MACE compared with moderate-dose statin therapy. The reduction in the incidence of TVR was independent of low-density lipoprotein cholesterol and C-reactive protein lowering and may therefore be due, at least in part, to a pleiotropic effect of high-dose statin therapy. (PROVE IT–TIMI 22; NCT00382460) (Source: Journal of the American College of Cardiology)

Coronary heart disease in moderately hypercholesterolemic, hypertensive black and non-black patients randomized to pravastatin versus usual care: The Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial (ALLHAT-LLT)

American Heart Journal — Tue, 01 Dec 2009 00:00:00 +0100

Conclusions: Our results suggest that pravastatin is effective in preventing CHD in blacks. (Source: American Heart Journal)

Laboratory and non-laboratory-based risk prediction models for secondary prevention of cardiovascular disease: the LIPID study

European Journal of Cardiovascular Prevention and Rehabilitation — Tue, 01 Dec 2009 00:00:00 +0100

Conclusion: A simpler non-laboratory-based risk prediction model performed equally as well as the more comprehensive laboratory-based risk prediction models. The risk chart based on the further simplified Score Model may provide a useful tool for clinical cardiologists to assess an individual patient's risk for recurrent CVD events. (Source: European Journal of Cardiovascular Prevention and Rehabilitation)

Pravastatin: Acute pancreatitis in an elderly patient: case report

Reactions — Mon, 30 Nov 2009 14:07:30 +0100

(Source: Reactions)

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Tolerability of Red Yeast Rice (2,400 mg Twice Daily) Versus Pravastatin (20 mg Twice Daily) in Patients With Previous Statin Intolerance

The American Journal of Cardiology — Mon, 30 Nov 2009 00:00:00 +0100

In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins. (Source: The American Journal of Cardiology)

Apolipoprotein E Genotype, Plasma Cholesterol, and Cancer: A Mendelian Randomization Study

American Journal of Epidemiology — Wed, 18 Nov 2009 04:11:06 +0100

Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard rat...

Validation of cell-based OATP1B1 assays to assess drug transport and the potential for drug-drug interaction to support regulatory submissions.

Xenobiotica — Tue, 17 Nov 2009 00:00:00 +0100

This study is focused on utilizing human embryonic kidney (HEK) 293 cell cultures genetically transfected with the human organic anion transporting polypeptides (OATP) 1B1 transporter to identify substrates and inhibitors in drug development. The kinetics of OATP1B1-mediated uptake of [(3)H]-oestradiol 17beta-glucuronide and inhibition of uptake by rifamycin SV were used to determine K(m), V(max), and IC(50) values over a range of passage numbers to investigate accuracy and precision. The mean K(m) and V(max) values were found to be 6.3 +/- 1.2 muM and 460 +/- 96 pmol min(-1) mg(-1), respectively. The mean IC(50) value for rifamycin SV was 0.23 +/- 0.07 muM on uptake of 1 muM [(3)H]-oestradiol 17beta-glucuronide. These data were similar to previously reported values (accuracy greater than ...

Differing effect of statins on insulin sensitivity in non-diabetics: A systematic review and meta-analysis

Diabetes Research and Clinical Practice — Fri, 13 Nov 2009 00:00:00 +0100

Conclusions: Statins do not appear to demonstrate a ‘class effect’ on IS in patients without diabetes. Differences between individual statins likely exist that may partially explain the findings of previously conducted meta-analyses examining the impact of statins on the development of diabetes. (Source: Diabetes Research and Clinical Practice)

Synergistic Anti-Fibrotic Efficacy of Statin and Protein Kinase C Inhibitor in Hepatic Fibrosis.

Am J Physiol Gastroi... — Thu, 12 Nov 2009 00:00:00 +0100

In conclusion, simultaneous treatment with statin and PKC inhibitor synergistically enhanced the anti-fibrotic efficacy in both in vitro and in vivo models of hepatic fibrosis and may therefore have therapeutic implication for reducing hepatic fibrosis. PMID: 19910526 [PubMed - as supplied by publisher] (Source: Am J Physiol Gastroi...)

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Endothelial Function in Subjects with Isolated Low HDL Cholesterol: Role of Nitric Oxide and Circulating Progenitor Cells.

American Journal of Physiology. Endocrinology and Metabolism — Tue, 10 Nov 2009 00:00:00 +0100

Authors: Higashi Y, Maysuoka H, Umei H, Sugano R, Fujii Y, Soga J, Kihara Y, Chayama K, Imaizumi T Epidemiologic studies have shown that a low level of high-density lipoprotein (HDL) cholesterol is a risk factor for cardiovascular diseases. The purpose of this study was to determine the contribution of isolated low HDL cholesterol to endothelial function. Thirty-nine subjects with low HDL cholesterol who had no other cardiovascular risk factors were selected from the 5417 participants from our population. We evaluated flow-mediated vasodilation (FMD) before and after 4 weeks of treatment with the HMG-CoA reductase inhibitor pravastatin in 29 of the 39 subjects with isolated low HDL cholesterol. FMD was lower in the low HDL cholesterol group (n=29) than in the control group (n=29), whil...

The kif6 719arg allele is associated with increased risk of coronary heart disease among males in the welcome trust case control consortium study of coronary heart disease

Atherosclerosis — Sun, 01 Nov 2009 00:00:00 +0100

Carriers of the KIF6 719Arg allele, compared with noncarriers, have a higher risk of coronary heart disease (CHD) in several prospective studies and in the placebo groups of two randomized trials of pravastatin. In these trials, pravastatin treatment ameliorated the risk associated with 719Arg allele. In the Welcome Trust Case-Control Consortium (WTCCC) CHD study, although no association was observed between the 719Arg allele and CHD, a significant association between the 719Arg allele and CHD was observed in a sex-differentiated test. In order to investigate this sex-differentiated association, we analyzed the association between the KIF6 polymorphism and CHD by comparing carriers of the 719Arg allele with noncarriers separately among males and females of the WTCCC CHD study. Among female...

Effects of increasing the dose of pravastatin on serum adiponectin level in Japanese mild hypercholesterolemic and hypertensive patients.

Arzneimittel-Forschung — Thu, 29 Oct 2009 16:28:02 +0100

In this study, increasing the dosage of pravastatin was investigated to determine whether it had a clearly favorable effect on the adiponectin level in hypercholesterolemic patients. A total of 26 mild hypercholesterolemic and hypertensive patients were enrolled in this study. The patients were initially treated with pravastatin 10 mg/day for 6 months or more, and then increased to pravastatin 20 mg/day. Serum adiponectin, cholesterol fractionated components, and lipoprotein components were evaluated after 6 months. Increasing the dose of pravastatin from 10 to 20 mg/day caused the low-density lipoprotein cholesterol levels to decrease (from 130 to 104 mg/dL, p < 0.001), and thereafter the serum adiponectin levels, particularly the high-molecular-weight adiponectin levels significantly ...

In vitro interactions between primycin and different statins in their effects against some clinically important fungi.

Journal of Medical Microbiology — Thu, 29 Oct 2009 00:00:00 +0100

Authors: Nyilasi I, Kocsube S, Pesti M, Lukacs G, Papp T, Vagvolgyi C The in vitro antifungal activities of primycin and various statins against some opportunistic pathogenic fungi were investigated. Primycin completely inhibited the growth of Candida albicans (MIC: 64 microg ml(-1)) and Candida glabrata (MIC: 32 microg ml(-1)), and was very effective against Paecilomyces variotii (MIC: 2 microg ml(-1)), but it had little effect on Aspergillus fumigatus, Aspergillus flavus or Rhizopus oryzae (MIC: >64 microg ml(-1)). The fungi exhibited different degrees of sensitivity to the statins; fluvastatin and simvastatin exerted potent antifungal activities against a wide variety of clinically important fungal pathogens. Atorvastatin, rosuvastatin and lovastatin were slightly effective again...

Efficacy of aggressive lipid controlling therapy for preventing saphenous vein graft disease.

The Annals of Thoracic Surgery — Tue, 27 Oct 2009 12:29:26 +0100

CONCLUSIONS: Prophylactic treatment for yellow plaque and thrombus formation are extremely important in the development of early and late SVG disease. Aggressive lipid controlling therapy is quite attractive to avoid post CABG SVG disease and may be effective to maintain the long-term graft patency. PMID: 19853088 [PubMed - in process] (Source: The Annals of Thoracic Surgery)

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Renal failure (chronic)

Clinical Evidence — Mon, 26 Oct 2009 23:00:00 +0100

New evidence; conclusions changed for: Statins versus placebo or no treatment One systematic review and two subsequent RCTs added. The review found that statins reduced all-cause mortality and cardiovascular mortality compared with placebo or no treatment. The first subsequent RCT found that simvastatin decreased all-cause mortality, major coronary events, and the composite outcome of death from coronary disease and non-fatal MI compared with placebo. The second subsequent RCT found no significant difference between pravastatin and placebo or no treatment in rates of progression to end-stage renal disease (ESRD), composite outcome of ESRD or 50% decrease in glomerular filtration rate (GFR), or the composite outcome of ESRD or 25% decrease in GFR. Categor...

Pravastatin use and cancer risk: a meta-analysis of individual patient data from long-term prospective controlled trials in Japan

Pharmacoepidemiology and Drug Safety — Mon, 26 Oct 2009 00:00:00 +0100

To assess the influence of pravastatin therapy on cancer morbidity and mortality by a meta-analysis of individual patient data (IPD) from three independent Japanese large-scale clinical trials.We conducted a meta-analysis of IPD collected from three large-scale prospective studies, the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study, Kyushu Lipid Intervention Study (KLIS), and Hokuriku Lipid Coronary Heart Disease Study-Pravastatin Atherosclerosis Trial (Holicos-PAT), which compared cardiovascular outcomes with pravastatin therapy and non-statin therapy in Japanese patients with hypercholesterolemia over a follow-up period of [ge]4 years. The incidence of cancer or cancer death in the pravastatin and non-statin therapy groups was compared b...

Efficacy of Aggressive Lipid Controlling Therapy for Preventing Saphenous Vein Graft Disease [ORIGINAL ARTICLES: ADULT CARDIAC]

The Annals of Thoracic Surgery — Thu, 22 Oct 2009 18:54:53 +0100

Conclusions Prophylactic treatment for yellow plaque and thrombus formation are extremely important in the development of early and late SVG disease. Aggressive lipid controlling therapy is quite attractive to avoid post CABG SVG disease and may be effective to maintain the long-term graft patency. (Source: The Annals of Thoracic Surgery)

Different effects of the ABCG2 c.421C>A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin

Future Medicine: Pharmacogenomics — Tue, 20 Oct 2009 16:09:34 +0100

Pharmacogenomics , October 2009, Vol. 10, No. 10, Pages 1617-1624. (Source: Future Medicine: Pharmacogenomics)

The SLCO1B1*5 Genetic Variant Is Associated With Statin-Induced Side Effects

Journal of the American College of Cardiology — Fri, 16 Oct 2009 12:49:44 +0100

Conclusions: SLCO1B1*5 genotype and female sex were associated mild statin-induced side effects. These findings expand the results of a recent genome-wide association study of statin myopathy with CK >3× normal to milder, statin-induced, muscle side effects. (Source: Journal of the American College of Cardiology)

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Is cyclosporine A transport inhibited by pravastatin via multidrug resistant protein 2?

European Journal of Clinical Pharmacology — Tue, 13 Oct 2009 08:15:18 +0100

Conclusions Based on these results, we suggest that CyA transport may be competitively inhibited by pravastatin via MRP2. Content Type Journal ArticleCategory Pharmacokinetics and DispositionDOI 10.1007/s00228-009-0740-6Authors Ryuji Kato, Osaka University of Pharmaceutical Sciences Laboratory of Clinical Pharmacy & Clinical Pharmacokinetics 4-20-1 Nasahara Takastuki Osaka 569-1094 JapanMami Nishide, Osaka University of Pharmaceutical Sciences Laboratory of Clinical Pharmacy & Clinical Pharmacokinetics 4-20-1 Nasahara Takastuki Osaka 569-1094 JapanChihiro Kozu, Osaka University of Pharmaceutical Sciences Laboratory of Clinical Pharmacy & Clinical Pharmacokinetics 4-20-1 Nasahara Takastuki Osaka 569-1094 JapanAsuka Iwamoto, Osaka University of Pharmaceutical Sciences Lab...

Biotechnological production and applications of statins.

Applied Microbiology and Biotechnology — Fri, 09 Oct 2009 23:00:00 +0100

Authors: Barrios-González J, Miranda RU Statins are a group of extremely successful drugs that lower cholesterol levels in blood; decreasing the risk of heath attack or stroke. In recent years, statins have also been reported to have other biological activities and numerous potential therapeutic uses. Natural statins are lovastatin and compactin, while pravastatin is derived from the latter by biotransformation. Simvastatin, the second leading statin in the market, is a lovastatin semisynthetic derivative. Lovastatin is mainly produced by Aspergillus terreus strains, and compactin by Penicillium citrinum. Lovastatin and compactin are produced industrially by liquid submerged fermentation, but can also be produced by the emerging technology of solid-state fermentation, that display...

Angiotensin II receptor blocker and statins lower elevated levels of osteopontin in essential hypertension—Results from the EUTOPIA trial

Atherosclerosis — Mon, 05 Oct 2009 00:00:00 +0100

Abstract: Background: Osteopontin is a pleiotropic cytokine that has been implicated as a key factor in the development of atherosclerosis, a major complication of hypertension. We have earlier shown that olmesartan reduces mediators of vascular inflammation in patients with hypertension and cardiovascular disease. We aimed at studying the effect of olmesartan and/or pravastatin on osteopontin plasma levels, and the association between vascular inflammation markers and osteopontin in hypertensive patients.Methods: We assessed a panel of vascular inflammation markers and osteopontin during 12 weeks of therapy with 20mg olmesartan (n=94) or placebo (n=96) in a prospective, double-blind, multi-center study in patients with essential hypertension (re-evaluation of the EUTOPIA trial blood sampl...

What is the available evidence for the use of statins in patients with renal impairment?

NeLM - Cardiovascular Medicine — Sun, 04 Oct 2009 23:00:00 +0100

Source: South West Medicines Information and Training Area: Evidence > Medicines Q & A Dyslipidaemia is a common complication of CKD and contributes to high CV morbidity and mortality of CKD patients. Post-hoc analyses of large-scale lipid-lowering trials have shown that the reduction of CV risk in patients with chronic renal failure was equivalent to the reduction achieved in patients without chronic renal failure. Prospective RCTs evaluating the efficacy and long-term safety of statins in reducing CV events and death in patients with established CKD are in progress. Meta-analyses of small RCT have shown that statin use leads to a modest reduction in proteinuria and rate of kidney function loss, especially in patients with pre-existing CV disease and renal disease. A sub-group an...

Decreasing risk of death by 80% at the cost of $12 per month

Clinical Cases and Images — Sun, 04 Oct 2009 11:56:00 +0100

High-risk patients who took 3 older drugs - statin, lisinopril, aspirin - cut risk of a heart attack or stroke by 80% (source: Reuters).All of those are on the Walmart's $4 list which means you can decrease your risk of death by 80% for $12 per month (if you have the risk factors)."Even in people who took it less than half the time, they got over a 60 percent drop in heart attacks and strokes," said Dr. R. James Dudl of Kaiser Permanente in California, whose study was published in the American Journal of Managed Care. "Those who took it more than half the time -- they got more like an 80 percent drop."It also suggests that people do not need to take a name-brand statin drug -- which Dudl said costs up to eight times more than a generic -- to achieve a major reduction in risks.From Twitter:...

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Novel synthetic inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity that inhibit tumor cell proliferation and are structurally unrelated to existing statins.

International Journal of Molecular Medicine — Thu, 01 Oct 2009 06:18:32 +0100

Authors: Perchellet JP, Perchellet EM, Crow KR, Buszek KR, Brown N, Ellappan S, Gao G, Luo D, Minatoya M, Lushington GH Pilot-scale libraries of eight-membered medium ring lactams (MRLs) and related tricyclic compounds (either seven-membered lactams, thiolactams or amines) were screened for their ability to inhibit the catalytic activity of human recombinant 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in vitro. A dozen of the synthetic compounds mimic the inhibition of purified HMG-CoA reductase activity caused by pravastatin, fluvastatin and sodium salts of lovastatin, mevastatin and simvastatin in this cell-free assay, suggesting direct interaction with the rate-limiting enzyme of cholesterol biosynthesis. Moreover, several MRLs inhibit the metabolic activity of L1210 t...

Statin therapy and risk of developing type 2 diabetes: a meta-analysis.

Diabetes Care — Wed, 30 Sep 2009 23:00:00 +0100

CONCLUSIONS: Although statin therapy greatly lowers vascular risk, including among those with and at risk for diabetes, the relationship of statin therapy to incident diabetes remains uncertain. Future statin trials should be designed to formally address this issue. PMID: 19794004 [PubMed - in process] (Source: Diabetes Care)

Early Statin Therapy in Acute Coronary Syndromes: The Successful Cycle of Evidence, Guidelines, and Implementation

Journal of the American College of Cardiology — Wed, 30 Sep 2009 16:18:48 +0100

That statins should be prescribed for patients before hospital discharge after an episode of acute coronary syndrome (ACS) is a Level of Evidence: 1A recommendation of the American College of Cardiology/American Heart Association Joint Task Force. This level of recommendation is based upon 2 clinical trials: the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) and PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy) trials. In the MIRACL trial, 3,086 patients with unstable angina or non–Q-wave myocardial infarction were randomized within 4 days of the event to atorvastatin 80 mg/day or to placebo and followed for 16 weeks. The primary composite end point occurred in 14.8% of atorvastatin patients and 17.4% of placebo patients, a 16% relative ...

Prevention of contrast-induced nephropathy by chronic pravastatin treatment in patients with cardiovascular disease and renal insufficiency.

Journal of Cardiology — Tue, 29 Sep 2009 21:14:39 +0100

CONCLUSIONS: Chronic pravastatin treatment before contrast media exposure was important for preventing CIN in patients with renal insufficiency. Also, reducing the dose of contrast media was important for preventing CIN in patients with high-baseline serum creatinine levels. PMID: 19782255 [PubMed - in process] (Source: Journal of Cardiology)

Rediscovering bile acid sequestrants

Diabetes, Obesity and Metabolism — Thu, 24 Sep 2009 23:00:00 +0100

Conclusions: Therefore, colesevelam should be the most effective and logical agent to add to a statin in the diabetic and insulin-resistant patient, because in addition to lowering cardiac risk it may prevent the development of diabetes, as well as improving glycaemic control in the established diabetic patient. (Source: Diabetes, Obesity and Metabolism)

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Quantitative Population Pharmacokinetic Analysis of Pravastatin Using an Enterohepatic Circulation Model Combined With Pharmacogenomic Information on SLCO1B1 and ABCC2 Polymorphisms.

The Journal of Clinical Pharmacology — Tue, 22 Sep 2009 23:00:00 +0100

Authors: Ide T, Sasaki T, Maeda K, Higuchi S, Sugiyama Y, Ieiri I The aims of this study were to develop a population pharmacokinetic (PPK) model for pravastatin pharmacokinetics with regard to enterohepatic circulation (EHC) and to evaluate effects of polymorphisms in SLCO1B1 and ABCC2 on the pharmacokinetic (PK) profile of pravastatin quantitatively. A total of 636 blood samples from 57 healthy male volunteers were used. The PPK analysis was carried out using nonlinear mixed effect modeling (NONMEM) and validated by a bootstrap analysis. The PK profile of pravastatin was best described by a model of EHC with Erlang's distribution. A covariate analysis revealed that SLCO1B1*15 significantly influenced relative bioavailability (Frel); Frel was increased 1.50- and 1.95-fold in participa...

Statins inhibit aminoglycoside accumulation and cytotoxicity to renal proximal tubule cells.

Biochemical Pharmacology — Tue, 22 Sep 2009 23:00:00 +0100

Authors: Antoine DJ, Srivastava A, Pirmohamed M, Park BK Nephrotoxicity due to renal proximal tubule accumulation of aminoglycoside (AG) antibiotics, such as gentamicin, represents a major clinical problem. Receptor-mediated endocytosis via the multi-ligand receptor megalin is thought to be a key mechanism in the cellular uptake of AGs and nephrotoxicity. This process can be modulated by the intracellular concentration of isoprenoid pyrophosphates derived from the processing of mevalonate by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. Post-translation modifications by isoprenoid pyrophosphates are necessary for GTP-binding protein function. Given that statins inhibit HMG-CoA reductase and therefore affect the concentration of isoprenoid pyrophosphates, we have tested the hypoth...

HPLC and mass spectrometry analysis of dolichol-phosphates at the cell culture scale.

Analytical Biochemistry — Sun, 13 Sep 2009 23:00:00 +0100

Authors: Haeuptle MA, Hülsmeier AJ, Hennet T Dolichols (Dol) are polyprenol lipids that are essential structural components of eukaryotic membranes. In addition, the phosphorylated derivatives of Dol function as lipid anchor of mono- and oligosaccharide precursors involved in protein glycosylation. The biological importance of Dol-phosphates (Dol-P) is illustrated by the severe outcome of human disorders linked to Dol biosynthetic defects, such as Dol-kinase deficiency. For characterization of inherited human diseases and evaluation of therapeutic trials, cultured cells often serve as a sole possible source for experimentation. Limited amounts of cell culture material render the quantitative analysis of Dol a challenging task. Here, we present HPLC and mass spectrometry based appr...

Differential effects of simvastatin and pravastatin on expression of Alzheimer's disease-related genes in human astrocytes and neuronal cells [Research Articles]

The Journal of Lipid Research — Mon, 07 Sep 2009 23:00:00 +0100

Inhibitors of HMG-CoA reductase (statins) are widely used medications for reduction of cholesterol levels. Statin use significantly reduces risk of cardiovascular disease but has also been associated with lower risk of other diseases and conditions, including dementia. However, some reports suggest that statins also have detrimental effects on the brain. We provide evidence that simvastatin and pravastatin have significantly different effects on expression of genes related to neurodegeneration in astrocytes and neuroblastoma (SK-N-SH) cells in culture. Simvastatin significantly reduced expression of ABCA1 in astrocytes and neuroblastoma cells (by 79% and 97%, respectively; both P < 0.001). Pravastatin had a similar but attenuated effect on ABCA1 in astrocytes (–54%, P < 0.001) ...

PRAVASTATIN SODIUMtablet [Glenmark Generics Inc., USA]

DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST) — Fri, 04 Sep 2009 05:00:00 +0100

Updated Date: Sep 4, 2009 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

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Clopidogrel/pravastatin/tenofovir disoproxil fumarate: Rhabdomyolysis in an HIV-positive patient: case report

Reactions — Mon, 24 Aug 2009 12:02:41 +0100

(Source: Reactions)

Seasonal Variation in Lipids: Should We Consider It More?

The American Journal of Cardiology — Sat, 22 Aug 2009 10:10:23 +0100

We read with interest the report by Tung et al, describing seasonal variation in the lipid status of a cohort of patients enrolled in the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE-IT–TIMI-22) study. The investigators found no differences in lipid levels at baseline, but with treatment, low-density lipoprotein (LDL) cholesterol levels were significantly higher in winter than in summer (+6.25% and +9.7% in the pravastatin and atorvastatin groups, respectively, p (Source: The American Journal of Cardiology)

Role of tissue factor in a mouse model of thrombotic microangiopathy induced by antiphospholipid antibodies

Blood — Wed, 19 Aug 2009 23:00:00 +0100

Using different mouse monoclonal and human antiphospholipid (aPL) antibodies, we developed a new animal model of renal injury that shares many features with thrombotic microangiopathy (TMA). We found that more than 1 mechanism/signaling pathway is involved in glomerular injury induced by aPL antibodies in this model. Both complement-dependent and complement-independent pathways were identified that lead to glomerular endothelial cell damage and renal function impairment. We also found that C5a-C5aR interaction is a crucial step for the activation of the coagulation cascade and glomerular injury induced by complement-activating antibodies. In addition, our studies demonstrated complement-independent mechanisms in which reactivity with β2 glycoprotein I (β2GPI) plays an important r...

Effects of Xuezhikang (血脂康) and pravastatin on circulating endothelial progenitor cells in patients with essential hypertension

Chinese Journal of Integrative Medicine — Tue, 18 Aug 2009 09:11:51 +0100

Conclusions Combined use of XZK or pravastatin with the anti-hypertensive therapy could increase the CEPCs number and improve their function in EH patients with the blood pressure controlled by antihypertensive drugs, leading to benefits independent of pressure-lowering effects. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s11655-009-0266-xAuthors Li Lu, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaJian-zhong Zhou, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaLi Wang, The First People’s Hospital of Jiulongpo District Chongqing 400020 ChinaTie-xu Zhang, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 China Journal Chinese Journal of ...

APOE and ABCB1 variants influence response to statin therapy

MedWire News - Lipidology — Mon, 17 Aug 2009 00:00:00 +0100

Polymorphisms in the apolipoprotein E gene significantly influence the response of patients’ low-density lipoprotein cholesterol to atorvastatin and pravastatin, report investigators. (Source: MedWire News - Lipidology)

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Down-regulation of RhoA is involved in the cytotoxic action of lipophilic statins in HepG2 cells

Atherosclerosis — Mon, 17 Aug 2009 00:00:00 +0100

Conclusions: RhoA inactivation and to a lesser extent Rho-kinase inhibition after depletion of GGPP is implicated in the etiology of mitochondrial membrane depolarization and subsequent caspase-dependent cell death induced by the lipophilic statin in HepG2 cells. (Source: Atherosclerosis)

Effects of rosuvastatin on electronegative LDL as characterized by capillary isotachophoresis: the ROSARY Study [Research Articles]

The Journal of Lipid Research — Sun, 16 Aug 2009 23:00:00 +0100

In conclusion, rosuvastatin effectively reduced both the vfLDL subfraction and sd-cm-LDL subfractions as analyzed by cITP. (Source: The Journal of Lipid Research)

A systematic review and meta-analysis on the therapeutic equivalence of statins

Journal of Clinical Pharmacy and Therapeutics — Thu, 13 Aug 2009 23:00:00 +0100

This study will use systematic review to compare the efficacy and safety profiles of different statins at different doses and determine the therapeutically equivalent doses of statins to achieve a specific level of low-density lipoprotein cholesterol (LDL-C) lowering effect.Methods: Publications of head-to-head randomized controlled trials (RCTs) of statins were retrieved from the Oregon state database (1966[ndash]2004), MEDLINE (2005-April of 2006), EMBASE (2005-April of 2006), and the Cochrane Controlled Trials Registry (up to the first quarter of 2006). The publications were evaluated with predetermined criteria by a reviewer before they were included in the review. The mean change in cholesterol level of each statin was calculated and weighted by number of subjects involved in each RCT...

Statins Block Calcific Nodule Formation of Valvular Interstitial Cells by Inhibiting {alpha}-Smooth Muscle Actin Expression.

Arteriosclerosis, Thrombosis and Vascular Biology — Wed, 12 Aug 2009 23:00:00 +0100

CONCLUSIONS: Our studies provide evidence of a causal relationship between VIC myofibroblastic activity and initial VIC calcific nodule formation. Furthermore, we demonstrate that pravastatin inhibition of calcific nodule formation is related to inhibition of myofibroblastic activity. PMID: 19679827 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)

Pravastatin and cognitive function in the elderly. Results of the PROSPER study

Journal of Neurology — Wed, 12 Aug 2009 15:47:28 +0100

Abstract Observational studies have given conflicting results about the effect of statins in preventing dementia and cognitive decline. Moreover, observational studies are subject to prescription bias, making it hard to draw definite conclusions from them. Randomized controlled trials are therefore the preferred study design to investigate the association between statins and cognition. Here we present detailed cognitive outcomes from the randomized placebo-controlled PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cognitive function was assessed repeatedly in all 5,804 PROSPER participants at six different time points during the study using four neuropsychological performance tests. After a mean follow-up period of 42 months, no difference in cognit...

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Identification of Genetic Variants Associated With Response to Statin Therapy.

Arteriosclerosis, Thrombosis and Vascular Biology — Sun, 09 Aug 2009 23:00:00 +0100

CONCLUSIONS: Carriers of APOE epsilon2 versus epsilon4 had significantly greater LDL-C reduction with atorvastatin and with pravastatin, and more frequently achieved a guideline-recommended LDL-C </=70 mg/dL. Polymorphisms in triallelic G2677T/A variant in ABCB1 were associated with the degree of LDL-C lowering with pravastatin. PMID: 19667110 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)

Tissue Distribution of Mevalonate Pyrophosphate Decarboxylase in Guinea Pig.

Biological and Pharmaceutical Bulletin — Wed, 05 Aug 2009 20:28:03 +0100

Authors: Shimatani M, Michihara A, Akasaki K We previously reported that mevalonate pyrophosphate decarboxylase (MPD) is located in the cytosol and that MPD level in the liver is higher than in other rat tissues. In the present study, we further investigated the tissue distribution of MPD in guinea pigs by immunoblotting using anti-rat MPD antiserum. When immunoblot analysis was carried out using guinea pig brain, the antiserum reacted with 46-kDa protein as well as a substance with the same molecular weight of MPD in mice. Protein of 46-kDa detected in guinea pig liver treated with 0.1% pravastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor indicating a liver-specific effect, was increased 3-fold as compared with nontreated guinea pigs; however, 46-kDa protein in the brain ...

Atorvastatin/pravastatin/simvastatin: Myalgia: 11 case reports

Reactions — Mon, 03 Aug 2009 10:55:12 +0100

(Source: Reactions)

New highly sensitive enzyme immunoassay for the determination of pravastatin in human plasma.

Talanta — Thu, 30 Jul 2009 10:24:09 +0100

Authors: Darwish IA, Al-Obaid AR, Al-Malaq HA New highly sensitive enzyme immunoassay (EIA) has been developed and validated for the determination of pravastatin (PRV) in human plasma samples. PRV was coupled to keyhole limpt hemocyanin (KLH) and bovine serum albumin (BSA) via its terminal carboxylic acid group by carbodiimide reagent. PRV-KLH conjugate was used as an immunogen for raising anti-PRV polyclonal antibody in rabbits. The generated anti-PRV antibody recognized PRV with high affinity and selectivity. PRV-BSA conjugate was immobilized onto microwell plates and used as a solid phase. The assay involved a competitive binding reaction between PRV, in plasma sample, and the immobilized PRV-BSA for the binding sites on a limited amount of the anti-PRV antibody. The anti-PRV antibo...

Rationale and design of assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (the ALPS-AMI) study.

Journal of Cardiology — Wed, 29 Jul 2009 07:54:53 +0100

CONCLUSION: This is the first multicenter trial to compare the effects and safety of lipophilic and hydrophilic statin therapy in Japanese patients with AMI. It addresses an important issue and could influence the use of statin treatment in the secondary prevention of coronary artery disease. PMID: 19632524 [PubMed - in process] (Source: Journal of Cardiology)

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Characteristic changes in coronary artery at the early hyperglycaemic stage in a rat type 2 diabetes model and the effects of pravastatin

British Journal of Pharmacology — Thu, 23 Jul 2009 23:00:00 +0100

Conclusions and implications: Under conditions of increased vascular superoxide production, endothelial function is retained in LAD in OLETF rats at the early hyperglycaemic stage, partly due to enhanced endothelial NOS protein expression. Inhibition of superoxide production may contribute to the beneficial vascular effects of pravastatin. (Source: British Journal of Pharmacology)

Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats

British Journal of Pharmacology — Wed, 22 Jul 2009 23:00:00 +0100

Conclusions and implications: Chronic treatment with pravastatin attenuated the increase of systolic blood pressure in SHR, prevented early LVH and improved vascular structure and function. These effects were accompanied by decreased measures of oxidative stress and improvements in NO production. (Source: British Journal of Pharmacology)

The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials

NeLM - Drug Class Focused Reviews — Thu, 16 Jul 2009 23:00:00 +0100

The objectives and inclusion criteria were clearly stated. A number of databases were searched for relevant studies and experts in the field were contacted to try to identify additional studies, thus reducing the potential for publication bias. The authors did not state whether any language restrictions were applied. Two reviewers independently assessed studies ... (Source: NeLM - Drug Class Focused Reviews)

[Research Articles] A novel method for oral delivery of apolipoprotein mimetic peptides synthesized from all L-amino acids

The Journal of Lipid Research — Mon, 13 Jul 2009 23:00:00 +0100

Administered subcutaneously, D-4F or L-4F are equally efficacious, but only D-4F is orally efficacious because of digestion of L-4F by gut proteases. Orally administering niclosamide (a chlorinated salicylanilide used as a molluscicide, antihelminthic, and lampricide) in temporal proximity to oral L-4F (but not niclosamide alone) in apoE null mice resulted in significant improvement (P < 0.001) in the HDL-inflammatory index (HII), which measures the ability of HDL to inhibit LDL-induced monocyte chemotactic activity in endothelial cell cultures. Oral administration of L-[113-122]apoJ with niclosamide also resulted in significant improvement (P < 0.001) in HII. Oral administration of niclosamide and L-4F together with pravastatin to female apoE null mice at 9.5 months of age for six m...

A novel method for oral delivery of apolipoprotein mimetic peptides synthesized from all L-amino acids [Research Articles]

The Journal of Lipid Research — Mon, 13 Jul 2009 23:00:00 +0100

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Additive benefits of pravastatin and aspirin to decrease risks of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analysis

Cardiovascular Revascularization Medicine — Tue, 30 Jun 2009 23:00:00 +0100

In randomized trials of secondary prevention, pravastatin and aspirin reduce risks of cardiovascular disease (CVD). Pravastatin has a predominantly anti-atherogenic effect and aspirin an antiplatelet effect. Whether they have additional clinical benefits has not been demonstrated. (Source: Cardiovascular Revascularization Medicine)

A HMGCR polymorphism is associated with relations between blood pressure and urinary sodium and potassium ratio in the Epic-Norfolk Study

Journal of the American Society of Hypertension — Tue, 30 Jun 2009 23:00:00 +0100

Abstract: A polymorphism in the HMGCR gene (rs17238540) was related to a lower response to pravastatin treatment and we aimed to investigate whether an interaction is present for this polymorphism on blood pressure (BP) and salt intake. Cross-sectional urinary sodium and potassium concentration and the polymorphism were assessed in a large population study. Participants with the mutated allele (G) had significantly higher BP than homozygous TT. There were highly significant positive trends between BP and urinary sodium:potassium ratio across quartiles in men, with less effect in women, especially women carrying the mutated allele, G. Multivariate regression showed a significant positive association between BP and the urinary sodium: potassium ratio that differed in men and women according ...

The Vytorin on Carotid Intima-Media Thickness and Overall Arterial Rigidity (VYCTOR) Study.

The Journal of Clinical Pharmacology — Sat, 27 Jun 2009 16:08:48 +0100

This study assessed the effect of 3 lipid-lowering therapies on the reduction of the carotid intima-media thickness (IMT) in high-risk coronary Mexican patients. The study was a randomized, comparative, and open clinical trial. Ninety high-risk coronary patients were allocated to 3 groups: pravastatin 40 mg, simvastatin 40 mg, and simvastatin 20 mg and ezetimibe 10 mg initially. If the therapeutic goals were not attained (<100 mg/dL of low-density lipoprotein cholesterol [LDL-C] for type C and <70 mg for type D), patients in group 1 received pravastatin 40 mg and ezetimibe 10 mg, group 2 received simvastatin 80 mg, and group 3 received simvastatin 40 mg and ezetimibe 10 mg. The primary endpoint was the change of IMT over the course of 1 year. The secondary endpoints were changes in L...

Inflammation markers may put elderly at higher risk for fatal heart attacks

WorldHealth.net — Fri, 26 Jun 2009 18:43:32 +0100

While inflammation is the body's immune response to injury, the medical community also believes that it impacts cardiovascular disease. In fact, previous studies have shown that there is a relationship between high levels of inflammation markers in the circulation and an increased risk of heart attack and stroke. Now a new study by a group of researchers from the University of Glasgow has been conducted to examine the relationship between three inflammation markers and fatal and nonfatal cardiovascular events.The researchers used data collected from an existing trial known as the Prospective Study of Pravastatin in the Elderly at Risk on participants between the ages of 70 and 82, who had or were at risk for cardiovascular disease. The researchers specifically looked at whether three in...

Association of Leukocyte Subtype Counts With Coronary Atherosclerotic Regression Following Pravastatin Treatment

The American Journal of Cardiology — Thu, 25 Jun 2009 23:00:00 +0100

The purpose of this study was to clarify the relation between differential leukocyte counts and inhibition of the development of coronary atherosclerosis in patients with coronary artery disease. A 6-month prospective study was conducted in 84 patients treated with pravastatin. Plaque volume, as assessed by volumetric analysis using intravascular ultrasound, decreased significantly by 12.6% (p (Source: The American Journal of Cardiology)

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Are Markers of Inflammation More Strongly Associated with Risk for Fatal Than for Nonfatal Vascular Events?

PLoS Medicine — Mon, 22 Jun 2009 23:00:00 +0100

In a secondary analysis of a randomized trial comparing pravastatin versus placebo for the prevention of coronary and cerebral events in an elderly at-risk population, Naveed Sattar and colleagues find that inflammatory markers may be more strongly associated with risk of fatal vascular events than nonfatal vascular events. (Source: PLoS Medicine)

Study Demonstrates Efficacy Of Pitavastatin In Elderly Patients

Cholesterol News From Medical News Today — Wed, 17 Jun 2009 10:00:00 +0100

New data presented showed that pitavastatin is an effective treatment for the management of dyslipidemia in elderly patients, with a similar safety and tolerability profile to low-dose pravastatin. The Phase III data were presented by Kowa, at the XV International Symposium on Atherosclerosis in Boston. (Source: Cholesterol News From Medical News Today)

Pravastatin prevents miscarriages in antiphospholipid antibody-treated mice

Journal of Reproductive Immunology — Mon, 15 Jun 2009 00:00:00 +0100

Abstract: Miscarriages in patients with antiphospholipid (aPL) antibodies have been attributed to thrombosis of placental vessels. However, we have shown that inflammation plays a crucial role in fetal injury. We identified tissue factor (TF), the major cellular activator of the coagulation cascade, as a key mediator in inflammation and fetal injury in aPL antibody-treated mice. We found that TF in maternal neutrophils was associated with fetal injury. TF expression in neutrophils contributes to the respiratory burst and subsequent trophoblast oxidative injury and pregnancy loss induced by aPL antibodies. We also analysed how TF contributes to neutrophil activation and trophoblast injury in this model. We showed that neutrophils from aPL antibody-treated mice express protease activated rec...

Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 Cells

PPAR Research — Wed, 10 Jun 2009 03:19:57 +0100

Statins increase peroxisome proliferator-activated receptor α (PPARα) mRNA expression, but the mechanism of this increased PPARα production remains elusive. To examine the regulation of PPARα production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPARα promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPARα promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPARα promoter. This enhancement may be mediated by statin-induced HNF-4α. (2) PPARα mRNA expression was increased by statin...

Conversion to Tacrolimus and Atorvastatin in Cyclosporine-treated Heart Transplant Recipients With Dyslipidemia Refractory to Fluvastatin

The Journal of Heart and Lung Transplantation — Sun, 31 May 2009 23:00:00 +0100

Conclusions: Conversion to tacrolimus and atorvastatin appears to be a safe and effective lipid-lowering therapy in CsA-treated heart transplant recipients with dyslipidemia refractory to fluvastatin. (Source: The Journal of Heart and Lung Transplantation)

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[Effect of intensive treatment with atorvastatin versus standard doses of statins on the risk of stroke. A meta-analysis from five randomized trials including 25,709 patients]

Revista de Neurologia — Sun, 31 May 2009 23:00:00 +0100

CONCLUSIONS: Intensive lipid lowering treatment with atorvastatin is associated with a 17% relative risk reduction of stroke in comparison with conventional doses of statins in secondary prevention population. PMID: 19472152 [PubMed - in process] (Source: Revista de Neurologia)

Effects of a concomitant single oral dose of rifampicin on the pharmacokinetics of pravastatin in a two-phase, randomized, single-blind, placebo-controlled, crossover study in healthy Chinese male subjects.

Clinical Therapeutics — Sun, 31 May 2009 23:00:00 +0100

CONCLUSION: Coadministration of a single oral dose of rifampicin significantly increased the plasma concentration of pravastatin in this group of healthy Chinese male subjects. PMID: 19695392 [PubMed - in process] (Source: Clinical Therapeutics)

Pleiotropic phenotypes caused by an opal nonsense mutation in an essential gene encoding HMG-CoA reductase in fission yeast

Genes to Cells — Sun, 24 May 2009 04:00:00 +0100

Schizosaccharomyces pombe genome contains an essential gene hmg1+ encoding the sterol biosynthetic enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Here, we isolated an allele of the hmg1+ gene, hmg1-1/its12, as a mutant that showed sensitivities to high temperature and to FK506, a calcineurin inhibitor. The hmg1-1 allele contained an opal nonsense mutation in its N-terminal transmembrane domain, yet in spite of the mutation a full-length protein was produced, suggesting a read-through termination codon. Consistently, overexpression of the hmg1-1 mutant gene suppressed the mutant phenotypes. The hmg1-1 mutant showed hypersensitivity to pravastatin, an HMGR inhibitor, suggesting a defective HMGR activity. The mutant treated with FK506 caused dramatic morphological changes and...

Pravastatin reduces stroke risk independently of LDL cholesterol reduction

MedWire News - Stroke — Tue, 12 May 2009 00:00:00 +0100

Patients with mild-to-moderate hypercholesterolemia treated with pravastatin have a significantly reduced risk for stroke independent of low-density lipoprotein cholesterol level compared with controls, report researchers from the MEGA study. (Source: MedWire News - Stroke)

Pravastatin reduces stroke risk independently of LDL cholesterol reduction

MedWire News - Lipidology — Tue, 12 May 2009 00:00:00 +0100

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Statins inhibit the growth of variant human embryonic stem cells and cancer cells in vitro but not normal human embryonic stem cells

British Journal of Pharmacology — Mon, 11 May 2009 04:00:00 +0100

Conclusions and implications: Normal hESCs were resistant to prolonged exposure to statins over a range of doses, compared with BG01V and MCF-7, probably because of genetic and behavioural differences. The statins not only have anti-cancer properties but can suppress abnormal hESCs thus promoting growth of normal hESCs in vitro. (Source: British Journal of Pharmacology)

Risk factors for stroke and lipid-lowering effect of pravastatin on the risk of stroke in Japanese patients with hypercholesterolemia: Analysis of data from the MEGA Study, a large randomized controlled trial

Journal of the Neurological Sciences — Thu, 07 May 2009 23:00:00 +0100

Conclusions: Male sex, aging, hypertension, diabetes, low HDL-C, high Lp(a), obesity, and smoking were determined as risk factors for stroke in Japanese patients with hypercholesterolemia, and the observed risk reduction could not be explained by pravastatin's LDL-C-lowering effect alone, suggesting pleiotropic effects. (Source: Journal of the Neurological Sciences)

Pravastatin and cardiovascular risk in moderate chronic kidney disease

Atherosclerosis — Thu, 07 May 2009 23:00:00 +0100

Abstract: Objectives: To investigate the relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) and retrospectively to evaluate the effect of low dose of pravastatin in Japanese hypercholesterolemic patients with CKD enrolled in the large-scale randomized MEGA Study.Methods: In this post hoc analysis, effect of low dose pravastatin treatment (10–20mg daily) on the primary prevention of the cardiovascular disease and renal function after 5 years was evaluated in 7196 patients with normal kidney function/mild CKD or moderate CKD. Patients were classified based on an estimated glomerular filtration rate (eGFR) ≥60 or 30– (Source: Atherosclerosis)

Fluvastatin improves osteoporosis in fructose-fed insulin resistant model rats through blockade of the classical mevalonate pathway and antioxidant action.

International Journal of Molecular Medicine — Fri, 01 May 2009 04:00:00 +0100

In this study, we evaluated whether osteoporosis might accelerate in fructose-fed rats (FFR), and examined the effect of fluvastatin through a blockade of the mevalonate pathway and an antioxidant action. Stimulation of recombinant receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) expressed by osteoblasts/ stromal cells and macrophage-colony stimulating factor (M-CSF) significantly increased TRAP-positive multinuclear osteoclasts and pit formation, accompanied by an increase in reactive oxygen species as assessed by dichlorodihydrofluorescein (DCF) staining. Interestingly, it was completely abolished by treatment with fluvastatin, pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC), but not pravastatin. These actions of fluvastatin were partially abolished by...

Rhabdomyolysis in an HIV-infected patient on anti-retroviral therapy precipitated by high-dose pravastatin.

Current Drug Safety — Thu, 30 Apr 2009 23:00:00 +0100

We report an HIV-infected patient receiving antiretroviral regimen consisting of atazanavir, ritonavir, emtricitabine and tenofovir who developed severe rhabdomyolysis approximately 4 months after increasing his pravastatin dose from 40 to 80 mg daily. His symptoms resolved within 10 days after the discontinuation of pravastatin and antiretroviral therapy. To our knowledge, this is the first case of rhabdomyolysis possibly caused by pravastatin in an HIV-infected patient. PMID: 19442105 [PubMed - in process] (Source: Current Drug Safety)

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Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury

Blood — Thu, 23 Apr 2009 04:00:00 +0100

In this study, we found that TF not only activates the coagulation pathway, but it also mediates sFlt-1 release in monocytes causing defective placental development and fetal death. Blockade of TF with a monoclonal antibody inhibited sFlt-1 release, prevented the pathological activation of the coagulation pathway, restored placental blood flow, prevented placental oxidative stress, and rescued pregnancies. We also demonstrated that pravastatin, by down-regulating TF expression on monocytes and trophoblasts, prevented placental damage and protected pregnancies in DBA/2-mated CBA/J mice. These studies indicate that TF is an important mediator in fetal death and growth restriction and that statins may be a good treatment for women with recurrent miscarriages and IUGR. (Source: Blood)

Statins Do Not Help Prevent Alzheimer's Disease, Review Finds

Statins News From Medical News Today — Wed, 15 Apr 2009 11:00:00 +0100

An increasing number of studies show that elevated serum cholesterol levels might be part of the cause of Alzheimer disease, but a new review of studies says that, even so, the most successful class of cholesterol-lowering medicines will not stave off the condition. Statins includes medications such as atorvastatin (Lipitor) and pravastatin (Pravachol), which are some of the best-selling drugs in the world. (Source: Statins News From Medical News Today)

Seasonal Variation in Lipids in Patients Following Acute Coronary Syndrome on Fixed Doses of Pravastatin (40 mg) or Atorvastatin (80 mg) (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 [PROVE IT-TIMI 22] Study)

The American Journal of Cardiology — Wed, 15 Apr 2009 04:00:00 +0100

Previous studies have shown seasonal variation in lipids. To understand whether this variation exists in patients with acute coronary syndromes receiving statins, we examined data from the PROVE IT-TIMI 22 Study. At baseline, no significant difference in low-density lipoprotein (LDL) cholesterol was observed when stratified by season. However, a statistically significant difference in high-density lipoprotein cholesterol between winter (37 mg/dl) and summer (39 mg/dl) was observed (p (Source: The American Journal of Cardiology)

Solubility of Form B Pravastatin Sodium in (Water + 2-Propanol)

Journal of Chemical and Engineering Data — Tue, 14 Apr 2009 19:28:43 +0100

Journal of Chemical & Engineering Data, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Chemical and Engineering Data)

Pravastatin confirmed as effective in moderate CKD

MedWire News - Lipidology — Thu, 09 Apr 2009 00:00:00 +0100

Treatment with pravastatin is associated with both cardiac and renal benefits in patients with moderately severe chronic kidney disease, a post hoc analysis of clinical trial data suggests. (Source: MedWire News - Lipidology)

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Efficient Biotransformations Using Escherichia coli with tolC acrAB Mutations Expressing Cytochrome P450 Genes.

Bioscience, Biotechnology, and Biochemistry — Tue, 07 Apr 2009 04:00:00 +0100

We report here some efficient biotransformations using Escherichia coli strains with disruptions for the AcrAB-TolC efflux pump system. Biotransformations of compactin into pravastatin (6alpha-hydroxy-iso-compactin) were performed using E. coli strains with tolC and/or acrAB mutations expressing a cytochrome P450 (P450) gene. The production levels of pravastatin using strains with acrAB, tolC, and tolC acrAB mutations increased by 3.7-, 7.0-, and 7.1-fold, respectively. Likewise, the production levels of 25-hydroxy vitamin D(3) and 25-hydroxy 4-cholesten 3-one using tolC acrAB mutant strains expressing an individual P450 gene increased by 2.2- and 16-fold, respectively. The enhancement of this biotransformation efficiency could be explained by increases in the intracellular amounts of subs...

Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease.

Neurobiology of Disease — Tue, 31 Mar 2009 04:00:00 +0100

Authors: Handattu SP, Garber DW, Monroe CC, van Groen T, Kadish I, Nayyar G, Cao D, Palgunachari MN, Li L, Anantharamaiah GM Recent evidence indicates that inflammation may significantly contribute to the pathogenesis of Alzheimer's disease (AD). Since the apo A-I mimetic peptide D-4F has been shown to inhibit atherosclerotic lesion formation and regress already existing lesions (in the presence of pravastatin) and the peptide also decreases brain arteriole inflammation, we undertook a study to evaluate the efficacy of oral D-4F co-administered with pravastatin on cognitive function and amyloid beta (Abeta) burden in the hippocampus of APPSwe-PS1DeltaE9 mice. Three groups of male mice were administered D-4F and pravastatin, Scrambled D-4F (ScD-4F, a control peptide) and pravastatin in ...

Skin ulcers and myopathy associated with pravastatin therapy.

Clinical And Experimental Dermatology — Mon, 23 Mar 2009 04:00:00 +0100

Authors: Fernández-Torres R, Del Pozo J, Almagro M, Yebra-Pimentel MT, Fernández-Jorge B, Mazaira M, Fonseca E PMID: 19323663 [PubMed - as supplied by publisher] (Source: Clinical And Experimental Dermatology)

[Research Articles] The synergistic inhibition of atherogenesis in apoE-/- mice between pravastatin and the sPLA2 inhibitor varespladib (A-002)

The Journal of Lipid Research — Tue, 17 Mar 2009 04:00:00 +0100

Secretory phospholipase A2 (sPLA2) activity promotes foam cell formation, increases proinflammatory bioactive lipid levels, decreases HDL levels, increases atherosclerosis in transgenic mice, and is an independent marker of cardiovascular disease. The effects of the sPLA2 inhibitor A-002 (varespladib) and pravastatin as monotherapies and in combination on atherosclerosis, lipids, and paraoxonase (PON) activity in apoE–/– mice were investigated. Male apoE–/– mice were placed on a 12-week high-fat diet supplemented with A-002 alone or combined with pravastatin. Atherosclerotic lesions were examined for size and composition using en face analysis, Movat staining, anti-CD68, and anti- actin antibodies. Plasma lipids and PON activity were measured. A-002 decreased athero...

Prognostic utility of apoB/AI, total cholesterol/HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: results from PROVE IT-TIMI 22.

Arteriosclerosis, Thrombosis and Vascular Biology — Sun, 01 Mar 2009 05:00:00 +0100

CONCLUSION: In the present study of ACS patients receiving statin therapy, on-treatment apoB/AI, TC/HDL, and non-HDL-C offered similar prognostic information to LDL-C. However, the addition of hs-CRP to lipid-based measurements significantly improved risk prediction. On treatment CRP measurement may therefore offer additive prognostic information to lipids in ACS patients. PMID: 19122170 [PubMed - indexed for MEDLINE] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)

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[Atorvastatin in secondary prevention]

Turk Kardiyoloji Dernegi arsivi — Sun, 01 Mar 2009 00:00:00 +0100

Authors: Ongen Z, Yilmaz Y, Karadağ B During the 10 years of atorvastatin availability in the Turkish market, the physicians have had the opportunity to observe the accumulation of data related to its beneficial effect on clinical endpoints. The scope of this review is limited to the trials concerning the role of atorvastatin in secondary prevention. In GREACE and ALLIANCE studies, the benefit of atorvastatin was demonstrated in patients with coronary heart disease in real-world setting. TNT was the first trial which showed that aggressive lipid lowering therapy was more protective than a moderate one in patients with stable coronary artery disease. In the MIRACL trial, 80 mg atorvastatin was compared with placebo and found effective in preventing ischemic events in patients with...

Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy

The Pharmacogenomics Journal — Thu, 26 Feb 2009 08:24:32 +0100

Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy The Pharmacogenomics Journal advance online publication, February 24, 2009. doi:10.1038/tpj.2009.3 Authors: Tomomi Furihata, Naoki Satoh, Tomoharu Ohishi, Miyuki Ugajin, Yoshio Kameyama, Kaori Morimoto, Sayaka Matsumoto, Keiko Yamashita, Kaoru Kobayashi & Kan Chiba (Source: The Pharmacogenomics Journal)

Statins may regenerate heart muscle

Health News - UPI.com — Mon, 23 Feb 2009 21:28:48 +0100

BUFFALO, N.Y., Feb. 23 (UPI) -- U.S. researchers show that the drug pravastatin, a statin, may be able to prevent the development of heart disease by regenerating diseased heart muscle. (Source: Health News - UPI.com)

HMG-CoA Reductase Inhibitors (Statins) Activate Expression of PPARα/PPARγ and ABCA1 in Cultured Gallbladder Epithelial Cells

Digestive Diseases and Sciences — Thu, 19 Feb 2009 14:44:35 +0100

In conclusion, statins probably contribute to the preservation of GBEC function by activation of PPARα and PPARγ, which have anti-inflammatory effects by suppression of pro-inflammatory cytokines, and ABCA1 activation mediated by LXRα, which prevents the accumulation of cholesterol in GBEC. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10620-009-0734-3Authors Jin Lee, Hallym University Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Hangang Sacred Heart Hospital 94-200, Youngdungpo-Dong, Youngdungpo-Gu Seoul KoreaEun Mi Hong, Hallym University Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Hangang Sacred Heart Hospital 94-200, Youngdungpo-Dong, Youngdungpo-Gu Seoul KoreaDong Hee Koh, Hall...

Rhabdomyolysis reports show interaction between simvastatin and CYP3A4 inhibitors

Pharmacoepidemiology and Drug Safety — Tue, 10 Feb 2009 05:00:00 +0100

To assess spontaneous reports of rhabdomyolysis associated with simvastatin (SV) and pravastatin (PV) for evidence of CYP3A4 interaction. Clinical trial results advocate cholesterol lowering in high-risk patients including diabetics and the elderly. Given the association between advancing age, metabolic, and cardiovascular disease, many patients are treated with concomitant medications upon statin initiation. Although statins are generally safe, minor and severe adverse reactions arise, especially when given to patients taking concomitant medications that inhibit the statin clearance and lead to increased statin plasma concentration.We conducted a comparative case series of rhabdomyolysis reports associated with SV and PV. Domestic spontaneous reports were obtained from the FDA's Adverse E...

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Survival analysis using inverse probability of treatment weighted methods based on the generalized propensity score

Pharmaceutical Statistics — Sun, 08 Feb 2009 05:00:00 +0100

In survival analysis, treatment effects are commonly evaluated based on survival curves and hazard ratios as causal treatment effects. In observational studies, these estimates may be biased due to confounding factors. The inverse probability of treatment weighted (IPTW) method based on the propensity score is one of the approaches utilized to adjust for confounding factors between binary treatment groups. As a generalization of this methodology, we developed an exact formula for an IPTW log-rank test based on the generalized propensity score for survival data. This makes it possible to compare the group differences of IPTW Kaplan-Meier estimators of survival curves using an IPTW log-rank test for multi-valued treatments. As causal treatment effects, the hazard ratio can be estimated using...

Adipocytokines and risk of stroke in older people: a nested case-control study

International Journal of Epidemiology — Mon, 02 Feb 2009 05:00:00 +0100

Conclusions Reduced adiponectin may have a modest role in the aetiology of ischaemic stroke in older people, however IL-18 and TNF are unlikely to play any important part. These adipocytokines do not have clinical predictive utility; history of prior cerebrovascular accident, known diabetes mellitus, prior disability and higher alcohol intake explain much of the stroke risk. (Source: International Journal of Epidemiology)

Pharmacogenomics: Inter-ethnic and Intra-ethnic Differences in Pharmacokinetic and Pharmacodynamic Profiles of Clinically Relevant Drugs.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan — Sun, 01 Feb 2009 05:00:00 +0100

Authors: Ieiri I, Higuchi S Intra- and inter-ethnic differences in pharmacokinetic and pharmacodynamic profiles of clinically relevant drugs are important issues not only for scenes of appropriate drug use in clinical settings but also for those of the drug development. Pharmacogenomics is extremely useful for understanding these racial differences. In this presentation, I will introduce pharmacogenomic concepts (e.g., single nucleotide polymorphisms (SNPs) and haplotype) for interpretation of racial differences in some drugs; pharmacogenomics of drug transporters such as OATP1B1 (organic anion transporting-polypeptide 1B1) and OCT1 (organic cation transporter 1) in pravastatin, metformin, and rosuvastatin will be discussed as model drugs. PMID: 19182452 [PubMed - in process] (Sour...

[Pharmacogenomics: inter-ethnic and intra-ethnic differences in pharmacokinetic and pharmacodynamic profiles of clinically relevant drugs]

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan — Sun, 01 Feb 2009 05:00:00 +0100

The relationship between reduction in low-density lipoprotein cholesterol by statins and reduction in risk of cardiovascular outcomes: An updated meta-analysis.

Clinical Therapeutics — Sun, 01 Feb 2009 05:00:00 +0100

Conclusions: Based on meta-regression analysis of these trials, there was a significant positive relationship between reduction in LDL-C and reduction in the risk for major cardiovascular events. These results support and extend the findings of the CTTC. PMID: 19302897 [PubMed - in process] (Source: Clinical Therapeutics)

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Pravastatin reduces CVD risk in hypertensives with mild dyslipidemia

MedWire News - Lipidology — Tue, 27 Jan 2009 10:12:05 +0100

A post hoc analysis of data from the MEGA study shows that hypertensive individuals with mild dyslipidemia have a significant reduction in cardiovascular disease risk after pravastatin therapy. (Source: MedWire News - Lipidology)

Pravastatin: Psoriasiform eruption transitioning to psoriasis (first report) in an elderly patient: case report

Reactions — Sat, 24 Jan 2009 07:16:13 +0100

(Source: Reactions)

A randomized, multicentre, open-label, parallel-group trial to compare the efficacy and safety profile of daming capsule in patients with hypercholesterolemia

Phytotherapy Research — Wed, 14 Jan 2009 05:00:00 +0100

To study the efficacy and tolerability of Daming capsule (DMC) in Chinese patients with hyperlipidemia, a randomized, multi-centre, open-label, parallel-group trial was conducted. Sixty enrolled patients with hyperlipidemia allocated to six medical centers were randomly divided into two groups of 30 individuals each. One group received DMC 2 g b.i.d. for 6 weeks, and the other received pravastatin 10 mg o.d. for 6 weeks. For efficacy assessment, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured before and after drug treatment. Serum TC and LDL-C levels in the DMC-treatment group were significantly decreased compared with those before treatment (p < 0.05), while TG and HDL-C levels did ...

Pravastatin Controls Airway Inflammation in Mouse Model of Allergic Asthma

Medscape Allergy Headlines — Tue, 13 Jan 2009 17:43:09 +0100

Pravastatin suppresses sensitization to allergens, down-regulates interleukin-17 (IL-17) production, and appears to suppress inflammation in general in the lungs of sensitized mice. Reuters Health Information (Source: Medscape Allergy Headlines)

Studies of Raising HDL Cholesterol: Updates at ESC 2008

Medscape Cardiology Headlines — Mon, 05 Jan 2009 18:32:06 +0100

ESC08: In addition to data-mining the famous 4S results, new results with pravastatin, ApoA-1 Milano, niacin, and fibrates support the next big step: raising HDL-C levels. Medscape Cardiology (Source: Medscape Cardiology Headlines)

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Prognostic Utility of ApoB/AI, Total Cholesterol/HDL, Non-HDL Cholesterol, or hs-CRP as Predictors of Clinical Risk in Patients Receiving Statin Therapy After Acute Coronary Syndromes. Results From PROVE IT-TIMI 22.

Arteriosclerosis, Thrombosis and Vascular Biology — Fri, 02 Jan 2009 05:00:00 +0100

CONCLUSIONS: In the present study of ACS patients receiving statin therapy, on-treatment apoB/AI, TC/HDL, and non-HDL-C offered similar prognostic information to LDL-C. However, the addition of hs-CRP to lipid-based measurements significantly improved risk prediction. On treatment CRP measurement may therefore offer additive prognostic information to lipids in ACS patients. PMID: 19122170 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)

Effect of the brand and generic medicine of pravastatin on dyslipidemia in rabbits fed a high cholesterol diet.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan — Thu, 01 Jan 2009 05:00:00 +0100

Authors: Kano S, Taguchi M, Hayase N, Kaneta S, Takaguri A, Ichihara K, Satoh K Mevalotin((R)) containing pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is the brand medicine and well known to be effective for patients with dyslipidemia. Now, more than 20 generic pravastatins are available for clinical therapy. We compared pharmaceutical property of Mevan((R)), a generic pravastatin, with that of Mevalotin((R)). According to the definition of the Japanese Pharmacopoeia, Mevalotin((R)) 10 mg tablets were uniform in pravastatin content, whereas 5 mg tablets were rather variable. Variation in pravastatin content of Mevan 5 mg tablets was the same as Mevalotin((R)) 5 mg, whereas that of 10 mg tablets was very variable. The plasma concentration of pravastatin in t...

Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell mobilisation and recruitment in apolipoprotein E knockout mice

Atherosclerosis — Mon, 29 Dec 2008 00:00:00 +0100

Abstract: Statins enhance incorporation of bone marrow-derived cells into experimental neointimal lesions. However, the contribution of progenitor cells to progression of spontaneous atherosclerotic plaques, and the possible modulatory role of statins in this process, remain poorly understood. We compared the effects of rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell mobilisation, recruitment into atherosclerotic plaques, and lesion growth. Statins were administered over 8 weeks to apolipoprotein E knockout mice on atherogenic diet. In addition, mice were lethally irradiated, followed by transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced lesion area and intima-to-media ratio at the brachiocephalic artery compared to vehicle, while bo...

Treatment With Statin on Atheroma Regression Evaluated by Intravascular Ultrasound With Virtual Histology (TRUTH Study).

Circulation Journal — Fri, 26 Dec 2008 05:00:00 +0100

Conclusion The treatment with statin on atheroma regression evaluated by intravascular ultrasound with Virtual Histology (TRUTH) study will be the first multicenter study using VH-IVUS to evaluate the effects of statins on changes in coronary artery plaque composition and the findings will clarify the mechanisms of coronary artery plaque stabilization. PMID: 19110505 [PubMed - as supplied by publisher] (Source: Circulation Journal)