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: 2.95). 12/2005; 19(6):403-14. DOI: 10.1007/s10557-005-5686-z
Source: PubMed

ABSTRACT 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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    ABSTRACT: Statins are associated with muscle myalgia and myopathy which likely reduce habitual physical activity. This is particularly relevant to older people who are less active, sarcopaenic, and at increased risk of stain myalgia. We hypothesised that statin myalgia would be allied to impaired strength and work capacity in older people, and determined whether differences aligned with divergences in lean mass, protein turnover, insulin sensitivity and the molecular regulation of these processes. Knee-extensor strength and work-output during 30 maximal isokinetic contractions were assessed in healthy male volunteers, 9 with no statin use (control 70.4±0.7yrs) and 9 with statin myalgia (71.5±0.9yrs). Whole-body and leg glucose disposal, muscle myofibrillar protein synthesis (MPS) and leg protein breakdown (LPB) were measured during fasting (≅5mU.l−1 insulin) and fed (≅40mU.l−1 insulin + hyperaminoacideamia) euglyceamic clamps. Muscle biopsies were taken before and after each clamp. Lean mass, MPS, LPB and strength were no different but work output during the initial 3 isokinetic contractions was 19% lower (p<0.05) in statin myalgic subjects due to a delay in time to reach peak power output. Statin myalgic subjects had reduced whole-body (p = 0.05) and leg (p<0.01) glucose disposal, greater abdominal adiposity (p<0.05), and differential expression of 33 muscle mRNAs (5% FDR); 6 of which, linked to mitochondrial dysfunction and apoptosis, increased at 1% FDR. Statin myalgia was associated with impaired muscle function, increased abdominal adiposity, whole body and leg insulin resistance and evidence of mitochondrial dysfunction and apoptosis.This article is protected by copyright. All rights reserved
    The Journal of Physiology 12/2014; · 4.38 Impact Factor
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    ABSTRACT: Background Statins are currently the preferred pharmacological therapy in individuals with familial hypercholesterolemia (FH) with the aim to prevent premature atherosclerosis. In adults, these agents have been proven to be safe and well tolerated; however, non-adherence is a significant clinical issue. Objectives In this study, we evaluated tolerability and adherence to statin therapy in young adult FH patients 10 years after this was initiated in their childhood. Methods A questionnaire including items on medical history, adherence and reasons for discontinuation was sent to 214 young adult FH patients that initiated statin therapy at least 10 years ago. Tolerability was defined as 100 % minus the percentage of patients that discontinued statin therapy due to side effects. Adherence was defined as the extent to which patients took their medication as prescribed by their physician. We labelled patients adherent if they took 80 % or more of their pills in the month preceding our assessment. Results Follow-up was successful in 205 (95.8 %) subjects (age 18–30 years). A history of side effects was reported by 40 (19.5 %) of the patients, and mainly consisted of muscle complaints and gastrointestinal symptoms. Three patients (1.5 %) discontinued statin therapy because of side effects. Rhadbomyolysis or other serious adverse events were not reported. In fact, 169 (82.4 %) of 205 patients remained on statin treatment and 78.7 % (148 out of 188) were adherent. None of the patient characteristics were significantly associated with adherence. Conclusions Individuals with FH who started statin therapy in childhood demonstrated good adherence during ten years of treatment. Furthermore, statin therapy was well tolerated; only a small minority discontinued therapy because of side effects and the side effects that were reported were mild in nature.
    Paediatric Drugs 02/2015; · 1.72 Impact Factor
  • Official journal of the South African Academy of Family Practice/Primary Care 08/2014; 53(3):205-215.


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