Myopathy with statin–fibrate combination therapy: clinical considerations

Abstract

Many patients who receive statin therapy for hyperlipidemia-such as patients with diabetes mellitus and metabolic syndrome--have residual cardiovascular risk. These patients often have dyslipidemia, including low levels of HDL cholesterol and elevated levels of triglycerides and small, dense LDL. For such patients, combination treatment with statins and fibrates is a potentially useful strategy to improve lipid and lipoprotein profiles and reduce cardiovascular risk. However, statin-fibrate combination regimens have potential adverse effects on skeletal muscle, including myopathy. To date, no large-scale, prospective, randomized, controlled trial has evaluated the safety and efficacy of statin-fibrate combination therapy; one such trial is underway but will not report data until 2010. Until then, clinicians need to consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic and other factors that can increase the systemic exposure of statins and/or fibrates and hence heighten the risk of toxic effects on muscles, as well as data from clinical trials and recommendations of consensus panels to optimize the safety of such combination regimens. On the basis of currently available data, fenofibrate or fenofibric acid is the fibrate of choice when used in combination with a statin because each is, in theory, associated with a lower risk of myopathy than gemfibrozil.

Opening a New Lipid “Apo-thecary”: Incorporating Apolipoproteins as Potential Risk Factors and Treatment Targets to Reduce Cardiovascular Risk

“…96,118,119 In summary, once maximally tolerated statin therapy has reduced Apo B to the lowest achievable levels, the clinician should consider adding niacin or a sequestrant to potentiate the Apo B− and cardiovascular risk-lowering effects of statins. Results from ongoing trials are eagerly awaited to evaluate the relative merits of combination treatment approaches.…”

Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia

“…Recently, new therapeutic reagents such as fibrates and statins have been created and primary dyslipidemia is effectively treated with these reagents [1]. However, they are not low priced and may induce rare but serious side effects such as rhabdomyolysis [1].…”

“…Recently, new therapeutic reagents such as fibrates and statins have been created and primary dyslipidemia is effectively treated with these reagents [1]. However, they are not low priced and may induce rare but serious side effects such as rhabdomyolysis [1]. Hypothyroidism induces secondary hypercholesterolemia that increases the incidence of atherosclerotic cardiovascular events [2], and replacement of low-hyperlipidemia was discovered and they were normal at that time, were also excluded.…”

Statin-Associated Polymyositis Following Omeprazole Treatment

“…Drugs of particular concern include CYP3A4 isoenzyme-dependent drugs such as macrolide antibiotics, azole antifungals, and cyclosporine, [12][13][14] drugs that interact with the glucuronidation pathway such as gemfibrozil, 12 and drugs that interact with the p-glycoprotein efflux system such as proton pump inhibitors (PPIs). 2,[15][16][17] There are many reports in the literature of an increased incidence of myopathy with use of statins combined with gemfibrozil, 18 as well as case reports of rhabdomyolysis and polymyositis associated with the use of omeprazole and other PPIs in combination with statin therapy. 2,19,20 In addition to the self-limited, toxic myopathy associated with statins, there are reports of statin-associated inflammatory myopathies including polymyositis, dermatomyositis, and necrotizing autoimmune myopathy that are characterized by elevated CK levels and proximal muscle weakness during or after statin use that persists even after discontinuation of the drug.…”