Mild to Moderate Muscular Symptoms with High-Dosage Statin Therapy in Hyperlipidemic Patients—The PRIMO Study

Université Victor Segalen Bordeaux 2, Burdeos, Aquitaine, France
Cardiovascular Drugs and Therapy (Impact Factor: 3.19). 12/2005; 19(6):403-14. DOI: 10.1007/s10557-005-5686-z
Source: PubMed


To characterize the risk factors, rate of occurrence, onset, nature and impact of mild to moderate muscular symptoms with high-dosage HMG-CoA reductase inhibitor (statin) therapy in general practice.
The Prédiction du Risque Musculaire en Observationnel (Prediction of Muscular Risk in Observational conditions, PRIMO) survey was an observational study of muscular symptoms in an unselected population of 7924 hyperlipidemic patients receiving high-dosage statin therapy in a usual care, outpatient setting in France. Information on patient demographics, treatment history and muscular symptoms was obtained by questionnaires.
Multivariate analysis revealed the strongest predictors for muscular symptoms to be a personal history of muscle pain during lipid-lowering therapy (odds ratio, OR, 10.12, 95% CI 8.23-12.45; P < 0.0001), unexplained cramps (OR 4.14; 95% CI 3.46-4.95; P < 0.0001) and a history of creatine kinase (CK) elevation (OR 2.04; 95% CI 1.55-2.68; P < 0.0001). Overall, muscular symptoms were reported by 832 patients (10.5%), with a median time of onset of 1 month following initiation of statin therapy. Muscular pain prevented even moderate exertion during everyday activities in 315 patients (38%), while 31 (4%) were confined to bed or unable to work. Fluvastatin XL was associated with the lowest rate of muscular symptoms (5.1%) among individual statins.
PRIMO demonstrated that mild to moderate muscular symptoms with high-dosage statin therapy may be more common and exert a greater impact on everyday lives than previously thought. Knowledge of the risk factors for muscular symptoms will allow identification and improved management of high-risk patients. The risk of muscular symptoms with fluvastatin XL treatment may be lower than with high dosages of other statins.

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Available from: Sylvie Dejager, Feb 03, 2015
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    • "Effect of Statins on Muscle Performance (STOMP) study, a randomized, placebo-controlled trial performed in 420 healthy adults, found no effects of 6 months of daily treatment with atorvastatin 80 mg on muscular strength or maximal aerobic capacity.[3]There are few studies in physically active adults. Only 20% of professional athletes tolerate statin therapy[7]and the incidence of statin myopathy is higher in more physically active individuals,[2,16]suggesting that statins may adversely affect skeletal muscle in physically active adults. Furthermore, statins are known to augment the creatine kinase increase after eccentric exercise,[17]and the increase in serum creatine kinase following a marathon is directly related to age in statin users (56 ± 8 years) but not in controls (51 ± 7 years),[8]suggesting that middle-aged endurance athletes on statins are more susceptible to exercise-induced muscle injury. "
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    ABSTRACT: Objectives: Physically active adults may be especially vulnerable to the adverse muscular side effects of statins. We determined if short-term cessation of statin therapy would improve aerobic exercise performance in middle-aged adults engaged in regular aerobic exercise training. Methods: Physically active middle-aged adults on statin therapy ≥6 mo (n = 16; 58 ± 10 y) or not taking lipid-lowering medications (controls) (n = 19; 51 ± 9 y) completed a peak oxygen consumption (VO2peak) and time to exhaustion test on a cycle ergometer 2-7 d apart. Tests were repeated following 1 mo of statin cessation or a 1 mo period for controls. Questionnaires were administered to assess exercise history and muscle complaints. Results: Statin users reported little or no muscle complaints and participation in aerobic exercise was similar between groups (p≥0.13). The lower VO2peak (37.3 ± 9.0 vs. 43.1 ± 4.9 ml/kg/min; p = 0.02) and time to exhaustion (21.9 ± 4.4 vs. 26.0 ± 6.3 min; p = 0.04) in statin users versus controls did not persist after controlling for age (p≥0.08). Aerobic exercise performance did not change with 1 mo of statin cessation (p≥0.54). No changes were observed in controls when tests were repeated 1 mo later (p≥0.38). Conclusion: Short-term cessation of statin therapy does not alter maximal aerobic capacity or aerobic endurance in physically active middle-aged adults with few or no statin muscle complaints.
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    • "Statins are extensively prescribed lipidlowering drugs that have contributed to increase survival rates in patients with cardiovascular disease.[1]A major drawback of these useful drugs is muscle toxicity , which affects a considerable number of patients and results in treatment discontinuation in 5–20%.[2]Myalgia, mild serum CK elevation and rhabdomyolysis are well-recognized musculoskeletal manifestations related to administration of these drugs. "
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    • "The prevalence of statin intolerance may be up to 10% in clinical practice. Risk factors for statin intolerance include older age, female sex, renal disease, history of muscle symptoms and high statin dose [5]. As these risk factors tend to be exclusion criteria for clinical trials, prevalence of statin intolerance in trials is lower compared to clinical practice [6]. "
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