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

ArticleinCurrent Atherosclerosis Reports 11(2):100-4 · April 2009with16 Reads
DOI: 10.1007/s11883-009-0016-8 · Source: PubMed
Abstract
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.
    • "In particular, it has been shown that statins display cholesterol-independent pleiotropic effects including antioxidative actions such as suppression of NADPH oxidase expression and activity [34,35], induction of antioxidant enzymes (SOD1, SOD3, and GPx) [36,37], prevention of eNOS uncoupling [34,35], and enhancement of eNOS expression and activity. All these beneficial properties are limited by well known side effects of statins; however, this restriction may be overcome by the use of a combination therapy with antioxidants [38]. Indeed, in patients with mixed hyperlipidemia, it has been observed that BPF administration enhances antioxidant properties of rosuvastatin inducing a significant reduction of oxidative stress in circulating polymorphonucleates (PMC). "
    Full-text · Article · Jan 2014
    • "The literature relating to the effect of statins on microalbuminuria is somewhat controversial. While some statin trials have reported a reduction in proteinuria [30] or no effect [31], some of the literature supports the findings in the current study that statins do have negative effects relating to the onset of proteinuria [19]. The main reason stated for atorvastatins' safety in relation to renal function is its somewhat unique method of metabolism; in that it has the least degree of renal excretion (2%), followed by fluvastatin (5%), rosuvastatin (10%), lovastatin (10%), simvastatin (13%), and pravastatin(20%) [32]. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Feb 2013
    • "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]. Contents lists available at ScienceDirect Fitoterapia j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / f i to t e This limits the use of statins and suggests the need of alternative therapeutic approaches. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Nov 2010
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