Atorvastatin treatment

Thrombocytopenia occurred in a 46-year-old man coinciding with atorvastatin treatment he had already tolerated simvastatin (12). 

Anfossi G, Massucco P, Bonomo K, Trovati M (2004) Prescription of statins to dyslipidemic patients affected by liver diseases a subtle balance between risks and benefits. Nutr Metab Cardiovasc Dis 14 215-224. Gomez-Dominguez E, Gisbert J, Moreno-Monteagudo J, Garcia-Buey L, Moreno-Otero R (2006) A pilot study of atorvastatin treatment in dys-lipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 23 1643-1647. 

Llaverias G, Pou J, Ros E, Zambon D, Cofan M, Sanchez A, Vazquez-Carrera M, Sanchez RM, Laguna JC, Alegret M (2008) Monocyte gene-expression profile in men with familial combined hyperlipidemia and its modification by atorvastatin treatment. Pharmacogenomics 9 1035-1054... 

Fig. 2 Effects of atorvastatin treatment on plasma cerebrosterol levels...

Atorvastatin when used in ACS has been shown to reduce events, and this offsets the upfront acquistion costs. The total expected cost was (British) X784.05 per patient in the placebo cohort and X851.59 per patient in the atorvastatin cohort, resulting in an incremental cost of 61.54 per patient in the atorvastatin group. The cost per event avoided was 1762.04. A third of the cost of atorvastatin treatment was offset within 16 weeks by the cost savings resulting from the reduction in the number of events in the atorvastatin cohort compared with the placebo cohort. 

Marchesi, S., Lupattelli, G., Siepi, D., ScMUaci, G., Vaudo, G., Roscini, AR., Sinzinger, H., and Maimarino, E. (2000) Short-Term Atorvastatin Treatment Improves Endothelial Function in Hypercholesterolemic Women, J. Cardiovasc. Pharmacol. 36,617-621. 

Knopp, R.H., Retzlaff, B.M., Fish, B., Dowdy, A., Twaddell, B., Nguyen, T., and Paramsothy, P., 2009. Slo-Niadn and atorvastatin treatment of lipoproteins and inflammatory markers in combined hyperlipidemia. Journal of... 

Tehrani S, Mobarrez F, Lins PE, Adamson U, Wallen HN, Jomeskog G. Impaired endotheliiun-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes. Diab Vase Dis Res 2013 10 483-8. 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol 2005 45(10) 1649-1653. 

The lipid regulator drugs bezafibrate and fenofibrate at initial concentrations of 4.5 and 4.2 ng g-1 in sterile sludge were completely removed after the fungal treatment. The fate of fenofibrate, also present in non-sterile sludge, was the same. Meanwhile, the most abundant atorvastatin, a cholesterol lowering statin, decreased its concentration in 80% and 65% in sterile and non-sterile conditions, respectively. 

Currently, there are a number of systemic and intestine-selective MTP inhibitors, including lomitapide (23, BMS-201038, AEGR-733), implitapide (24), JTT-130, SLx-4090, and R-256918 (latter three structures not disclosed) believed to be in active development [60]. In a meta-analysis of three Phase II clinical trials, lomitapide as monotherapy or in combination with ezetimibe, atorvastatin, or fenofibrate significantly reduced LDL cholesterol (up to 35% as monotherapy and 66% in combination with atorvastatin) and was well tolerated with less than 2% discontinuation due to abnormal liver function [61]. Lomitapide has also been granted orphan drug status for the treatment of homozygous familial hypercholesterolemia [59]. Results of a Phase II study of JTT-130 for type 2 diabetes are expected in August 2010 [59,60]. 

Homozygous familial hypercholesterolemia - 10 to 80 mg/day. Use atorvastatin as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) in these patients or if such treatments are unavailable. 

Elderly In patients older than 70 years of age, the AUC of lovastatin, pravastatin, and simvastatin is increased. Pravastatin does not need dosage adjustment. The safety and efficacy of atorvastatin, rosuvastatin, and lovastatin extended-release in patients 70 years of age and older were similar to those of patients younger than 70 years of age. Elderly patients (65 years of age and older) demonstrated a greater treatment response in respect to LDL-C, total-C and LDL/HDL ratio than patients younger than 65 years of age. 

Children Atorvastatin, simvastatin, and lovastatin are indicated for treatment of patients 10 to 17 years of age with heterozygous familial hypercholesterolemia. Pravastatin is indicated for the treatment of patients 8 to 18 years of age with heterozygous familial hypercholesterolemia. Safety and efficacy have not been established for atorvastatin, simvastatin, and lovastatin in prepubertal patients and patients younger than 10 years of age. Safety and efficacy have not been established in patients younger than 8 years of age for pravastatin. Safety and efficacy have not been established in patients younger than 18 years of age for fluvastatin. Safety and efficacy of rosuvastatin have not been established in pediatric patients. 

Monitoring For lovastatin, perform LFTs before initiating therapy, at 6 and 12 weeks after initiation of therapy or after dose elevation, and periodically thereafter (approximately 6-month intervals). For rosuvastatin, fluvastatin, and atorvastatin, it is recommended that LFTs be performed prior to and at 12 weeks following both the initiation of therapy and any elevation in dose, and periodically (eg, semiannually) thereafter. For pravastatin and simvastatin, perform LFTs prior to the initiation of therapy, prior to elevation of dose, and when otherwise clinically indicated. For patients titrated to the 80 mg dose of simvastatin, perform LFTs prior to titration, 3 months after titration to the 80 mg dose, and periodically thereafter (eg, semiannually) for the first year of treatment. Pay special attention to patients who develop elevated serum transaminase levels. If transaminase levels progress. 

Fluvastatin, launched in 1994, was the first S5mthetic HMG-CoA reductase inhibitor to be approved for the treatment of hypercholesterolemia. This statin was developed by Novartis (Sandoz), and it is marketed as a racemate under the trade name Lescol (Asberg and Holdaas, 2004). In laboratory studies, fluvastatin was shown to potently inhibit HMG-CoA reductase (IC50 = 8 nM) and effectively block cholesterol biosynthesis in hepatoc5de cells (IC50 = 52 nM) (Parker et al., 1990). Clinically, fluvastatin is prescribed less frequently than simvastatin, atorvastatin, or rosuvastatin, but it nevertheless remains an important medication for the treatment of hypercholesterolemia moreover, as the first completely S5mthetic statin to be approved, it offers a compelling synthetic story (Repic et al., 2001). 

Atorvastatin is an HMG Co-A reductase inhibitor. Pooled data from 21 completed and 23 continuing trials representing 3000 patient-years have shown that constipation, flatulence, dyspepsia, abdominal pain, headache, and myalgia occur in 1-3% of patients. Under 2% of atorvastatin-treated patients discontinued treatment because of an adverse event (1). Serious events in this review amounted to one patient with pancreatitis and one with cholestatic jaundice (1). There were no differences in adverse effects in 177 patients randomized for 52 weeks to either simvastatin or atorvastatin (2). 

Co-enzyme Q10 concentrations were measured in blood from hypercholesterolemic subjects before and after exposure to atorvastatin 80 mg/day for 14 and 30 days in 34 subjects eligible for statin treatment (11). The mean blood concentration of co-enzyme Q10 was 1.26 pg/ml at baseline, and fell to 0.62 after 30 days of atorvastatin therapy. There was a statistically significant fall detectable after 14 days of treatment. The authors concluded that widespread inhibition of co-enzyme Q10 synthesis could explain the exercise intolerance, myalgia, and myoglobinuria that are observed with statin treatment. 

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