The relationship of statins to rhabdomyolysis, malignancy, and hepatic toxicity: Evidence from clinical trials

Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
Current Atherosclerosis Reports (Impact Factor: 3.42). 04/2009; 11(2):100-4. DOI: 10.1007/s11883-009-0016-8
Source: PubMed


3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are among the most commonly prescribed and studied drugs in modern medicine. Their proven benefit in prevention of cardiovascular events is driven by their ability to markedly reduce low-density lipoprotein cholesterol (LDL-C). Recent analyses have provided insight into the relationship between statin-induced reductions in LDL-C and risk of rhabdomyolysis, liver toxicity, and cancer. Risk of statin-associated elevated liver enzymes and rhabdomyolysis is not related to the magnitude of LDL-C lowering. Instead, drug- and dose-specific effects of statins are more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, although there is an inverse association between LDL-C and cancer risk in both statin-treated and comparable control cohorts, statin therapy, despite significantly reducing LDL-C, is not associated with an increased risk of cancer.

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    • "Statins, like all other pharmacological treatments, inevitably have adverse side effects. The muscular system, hepatic function, and renal function have been documented to be affected by statin treatment [18] [19]. In general, large-scale randomized clinical trials have consistently demonstrated that statin therapy causes only a slight increased risk of side effects compared with placebo [20] [21]. "
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    ABSTRACT: Objectives . To investigate the efficacy and the safety of the three most commonly prescribed statins (rosuvastatin, atorvastatin, and pravastatin) for managing dyslipidemia among diabetic patients in Qatar. Subjects and Methods . This retrospective observational population-based study included 350 consecutive diabetes patients who were diagnosed with dyslipidemia and prescribed any of the indicated statins between September 2005 and September 2009. Data was collected by review of the Pharmacy Database, the Electronic Medical Records Database (EMR viewer), and the Patient's Medical Records. Comparisons of lipid profile measurements at baseline and at first- and second-year intervals were taken. Results . Rosuvastatin (10 mg) was the most effective at reducing LDL-C (29.03%). Atorvastatin reduced LDL-C the most at a dose of 40 mg (22.8%), and pravastatin reduced LDL-C the most at a dose of 20 mg (20.3%). All three statins were safe in relation to muscular and hepatic functions. In relation to renal function, atorvastatin was the safest statin as it resulted in the least number of patients at the end of 2 years of treatment with the new onset of microalbuminuria (10.9%) followed by rosuvastatin (14.3%) and then pravastatin (26.6%). Conclusion . In the Qatari context, the most effective statin at reducing LDL-C was rosuvastatin 10 mg. Atorvastatin was the safest statin in relation to renal function. Future large-scale prospective studies are needed to confirm these results.
    02/2013; 2013(25, article 3143):146579. DOI:10.1155/2013/146579
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    • "Despite the significant clinical benefits provided by statins [1], many patients, in particular those with metabolic syndrome, do not achieve their recommended low-density and high-density lipoprotein (LDL, HDL) cholesterol target goals with statins [3]. Moreover, the use of statins is forbidden in more than 40% of patients eligible for this therapeutic approach, mostly for the occurrence of side effects including myalgia, myopathy or liver disease and rhabdomyolysis in more severe cases [4] [5]. Fitoterapia 82 (2011) 309–316 Abbreviations: LDL, Low Density Lipoprotein; HDL, High Density Lipoprotein; BPF, Bergamot Polyphenol Fraction; HMG-CoA, 3-hydroxy-3- methylglutaryl-CoA reductase; CVD, Cardiovascular Diseases; totChol, total blood cholesterol; TG, triglycerides. "
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    ABSTRACT: Bergamot juice produces hypolipemic activity in rats though the mechanism remains unclear. Here we investigated on the effect of bergamot extract (BPF) in diet-induced hyperlipemia in Wistar rats and in 237 patients suffering from hyperlipemia either associated or not with hyperglycaemia. BPF, given orally for 30 days to both rats and patients, reduces total and LDL cholesterol levels (an effect accompanied by elevation of cHDL), triglyceride levels and by a significant decrease in blood glucose. Moreover, BPF inhibited HMG-CoA reductase activity and enhanced reactive vasodilation thus representing an efficient phytotherapeutic approach in combating hyperlipemic and hyperglycaemic disorders.
    Fitoterapia 11/2010; 82(3):309-16. DOI:10.1016/j.fitote.2010.10.014 · 2.35 Impact Factor
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    ABSTRACT: Treatments with ezetimibe/simvastatin (combined or alone) have been indicated as very promising approaches to strongly reduce cholesterol levels in hyperlipidemic patients. We will discuss the efficacy and safety of ezetimibe/simvastatin and their potential to reduce atheroprogression. The molecular mechanisms underlying the possible benefits in atherosclerosis and its complications will also be described. Combined therapy with ezetimibe/simvastatin has been shown to improve lipid profile inducing a very rapid reduction of low-density lipoprotein cholesterol levels in clinical trials. In the near future, potential clinical benefits could be observed in the IMPROVE-IT or SHARP trials. Although clinical studies are needed to further confirm safety of ezetimibe/simvastatin therapy, the greater efficacy in lipid-lowering was not associated with the increase of adverse events. Also the possible association between ezetimibe and cancer, which was observed in the SEAS trial, was not confirmed by further studies and meta-analyses. At present, ezetimibe should be considered an effective lipid-lowering agent that can be used in conjunction with simvastatin at the beginning of therapy, or included in the treatment of patients who do not achieve their low-density lipoprotein cholesterol goal with statins alone.
    Expert Opinion on Drug Safety 11/2009; 8(6):715-25. DOI:10.1517/14740330903282745 · 2.91 Impact Factor
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