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

Department of Endocrinology, Hôpital de la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris 83 Bd de L'Hôpital, 75 013, Paris, 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.

Download full-text


Available from: Sylvie Dejager, Feb 03, 2015
415 Reads
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To verify the safety and effectiveness of traditional Chinese red yeast rice-extract (RYR) for reduction of LDL cholesterol. Systematic literature review and meta-analysis. Medline and EMBASE were searched until November 2014. We selected randomized studies in which RYR with a known content of the active substance monacolin K was tested against placebo or an active control group. Outcome measures were the effect of RYR on LDL cholesterol and incidence of adverse reactions with emphasis on liver and kidney injury and muscle symptoms. Twenty studies were analyzed. Quality of safety assessment was low in the majority of studies. RYR lowered LDL cholesterol with 1.02 mmol/L [-1.20; -0.83] compared to placebo. Effect of RYR on LDL was not different from statin therapy (0.03 mmol/L [-0.36; 0.41]). The incidence of liver and kidney injury was 0-5% and the risk was not different between treatment and control groups (risk difference -0.01 [-0.01; 0.0] and 0.0 [-0.01; 0.02]). RYR exerts a clinically and statistically significant reduction of 1.02 mmol/L LDL cholesterol. Only when the mild profile of adverse reactions can be affirmed in studies with adequate methodology for safety assessment, RYR might be a safe and effective treatment option for dyslipidemia and cardiovascular risk reduction in statin intolerant patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 04/2015; 240(2):415-423. DOI:10.1016/j.atherosclerosis.2015.04.004 · 3.99 Impact Factor
  • Source
    • "The frequency of muscular effects under statin therapy is estimated to range between 5 and 20% in case series or observational studies and between 1.5 and 5% in randomized studies [1]. In the PRIMO observational study of 7924 dyslipidemic patients receiving a statin in France, the frequency of muscular symptoms was 10.5% [3]. The muscular effects of statins are variable and can manifest as an isolated elevation of CK levels without clinical symptoms or may be felt as myalgia, myositis or rhabdomyolysis , or immune-mediated necrotizing myopathy [1, 2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Statins are widely used in the treatment of hypercholesterolemia and their side effects on muscles are well established. Conversely, data are sparse regarding the safety of this class of drugs in subjects who engage in sports, particularly those who have intense sports activity. We report the case of a marathon runner who presented with acute rhabdomyolysis during competition while being under rosuvastatin treatment. This case raises the question of the need for temporary discontinuation of statin therapy when intense physical activity is planned.
    03/2015; 2015:1-2. DOI:10.1155/2015/721078
  • Source
    • "Its occurrence is much more prevalent in daily clinical practice than reported in randomized controlled trials (RCTs; 3–5%), since patients prone to these adverse events may have been excluded from participation during the run-in phase prior to randomization, and due to selection of patients in trials with lesser complexity of illness and comorbidities [12] [13]. Muscle-related adverse effects often lead to cessation of statin use, with consequent failure to lower low-density lipoprotein cholesterol (LDL-C) to target levels for primary and secondary prevention of CVD [12] [13] [14] [15]. Genetic predisposition, high drug dose, low body mass index (BMI), female gender, hypothyroidism, parathyroid dysfunction, underlying fibromyalgia or polymyalgia rheumatica, autoimmune phenomena , disturbances in muscle metabolism, alcohol abuse, low plasma vitamin D (vit D) level, drug interaction, as well as renal and hepatic dysfunction have been suggested as etiological factors [18] [19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. Methods: The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantitative data synthesis was performed using a fixed-effect model. Results: The electronic search yielded 437 articles; of those 20 were scrutinized as full texts and 13 studies were considered unsuitable. The final analysis included 7 studies with 2420 statin-treated patients divided into subgroups of patients with (n=666 [27.5%]) or without (n=1754) myalgia. Plasma vit D concentrations in the symptomatic and asymptomatic subgroups were 28.4±13.80ng/mL and 34.86±11.63ng/mL, respectively. The combination of data from individual observational studies showed that vit D plasma concentrations were significantly lower in patients with statin-associated myalgia compared with patients not manifesting this side effect (weighted mean difference -9.41ng/mL; 95% confidence interval: -10.17 to -8.64; p<0.00001). Conclusions: This meta-analysis provides evidence that low vit D levels are associated with myalgia in patients on statin therapy. Randomized controlled trials are necessary to establish whether vitamin D supplementation reduces the risk for statin-associated myalgia.
    International Journal of Cardiology 10/2014; 178. DOI:10.1016/j.ijcard.2014.10.118 · 4.04 Impact Factor
Show more