Clinical Manifestations of Adverse Effects of Statins, Oxidative Stress and Possible Role of Antioxidants in Prevention?

Abstract

Abstract:Background: There is evidence that statins are potent and effective agents with several pleiotropic effects for treatment of coronary artery disease(CAD). Statin may have adverse effects, if given in higher doses and in combinations.Methods: Internet search till 2009 and discussion with colleagues.Results: Statins are wonder drugs influencing wide range of physiological, biochemical,and biological functions.This list appears to be quite large and includes hypolipidemic, vasodilative, antithrombotic, antioxidant, antiinflammatory, antiproliferative, anticoagulant, agiogenic and bone formation inducing functions. Myopathy is the most frequent side effect of statins and in some cases may have a form of severe rhabdomyolysis. Less common adverse effects include hepatotoxicity, peripheral neuropathy, impaired myocardial contractility and autoimmune diseases. Rare manifestations of statin intolerance may be; pulmonary, psychiatric, ophthalmic and amyotropic lateral sclerosis. The risk of these unfavorable effects is largely outweighed by great reduction of cardiovascular events in statin users. The spectrum of statin-related myopathy ranges from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. Observational studies suggest that myalgia can occur in up to 10% of persons prescribed statins, whereas rhabdomyolysis continues to be rare. The mechanisms of statin-related myopathy are unclear. The criteria of diagnosis of myopathy do not bother about the symptoms of patients and oxidative stress, in absence of raised muscle enzymes.Coenzyme Q10 and other antioxidants are not considered in the prophylaxis of statin toxicity. Because one study showed no decrease in CoQ in the muscle in presence of toxicity, although several studies indicate a reduction in serum levels. Conclusion:Statins would be used more commonly in near future due to their cholesterol lowering and antiinflammatory effects. There would be a marked increase in the Number of patients with statin toxicity. Several studies have reported a significant reduction in the serum CoQ in patients receiving statins.Such concern has also been expressed by the International College of Cardiology in their meeting in April 2002April and 2005April and 2009, proposing that coenzyme Q10 and other antioxidants should be considered in the prevention as well as treatment of statin intoxication.

Is there is Need for Ubiquinone (CoQ10) Supplementation in Statin- Associated Myopathy?

“…These subjects are often intolerant of other lipid lowering therapies in addition to statins, which suggests that the myopathy is due to lipidlowering itself more than a simple pharmacokinetic reaction to high statin levels. Altogether, these findings support the concept that statin myopathy is a metabolic muscle disease [14].…”

“…Higher risk patients for statin myopathy are those with advanced age, females, with a small body frame and frailty, on higher statin doses, on other medications, or with other systemic diseases including hepatic or renal diseases, diabetes mellitus, or hypothyroidism [14]. For example, thin elderly women may represent a demographic category with increased risk for creatine kinase elevations greater than 10 times the upper limit of normal with statin therapy because 5% to 7% of women who received cerivastatin, 0.4 to 0.8 mg/d, had these creatine kinase elevations [23].…”

“…Genetic predisposition to statin myopathy is a rapidly expanding area of investigation. Genes of interest include those involved in the pharmacokinetics of the statin response, muscle atrophy, exercise intolerance, pain perception, and mitochondrial energy metabolism [14]. Common DNA polymorphisms in genes encoding cytochrome P450 enzymes, intestinal P-glycoproteins, and organic aniontransporting polypeptide are inconsistently associated with statin myopathy [32][33][34][35][36][37].…”

“…It also has been shown that increased levels of CoQ10 may protect cells from chemotherapy-induced oxidative stress [52]. It is suggested that prior or simultaneous administration of antioxidants may be protective against P450 induced cell damage by the statins, resulting in decrease of statin toxicity [14].…”

Pattern and incidence of adverse drug reactions observed in cardiac clinic of tertiary hospital, Hakeem Abdul Hameed Centenary Hospital, Jamia Hamdard, New Delhi

“…These were followed by other drugs. 19 Myopathy is the most common side effect of statins some less common side effects are peripheral neuropathy, impaired myocardial contractility and autoimmune diseases. However, the risks are outweighed by the greater reduction of cardiovascular events in statin users.…”