Predictors and outcomes of increases in creatine phosphokinase levels or rhabdomyolysis risk during statin treatment.


van Staa, TP; Carr, DF; O'Meara, H; McCann, G; Pirmohamed, M; (2014) Predictors and outcomes of increases in creatine phosphokinase levels or rhabdomyolysis risk during statin treatment. British journal of clinical pharmacology. ISSN 0306-5251 DOI: https://doi.org/10.1111/bcp.12367

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Abstract

AIM To evaluate clinical risk factors associated with myotoxicity in statin users. METHODS Cohort study of patients prescribed a statin in UK primary care practices contributing to the Clinical Practice Research Datalink. Outcomes of interest were creatine phosphokinase (CPK) levels and clinical records of rhabdomyolysis. RESULTS The cohort comprised 641703 statin users. Simvastatin was most frequently prescribed (66.3%), followed by atorvastatin (24.4%). CPK was measured in 127209 patients: 81.4% within normal range and 0.7% above 4(+) x upper limit of normal (ULN). Rhabdomyolysis was recorded in 59 patients. Patients with concomitant prescribing of CYP3A4-interacting drugs had an increased odds ratio (OR) of rhabdomyolysis compared with controls (OR 3.71, 95% CI 1.18-11.61) and 4(+) x ULN CPK compared with normal CPK (OR 1.28, 95% CI 1.01-1.60). Rosuvastatin users had higher risk of 4(+) x ULN CPK (OR 1.62, 95% CI 1.22-2.15) as did patients with larger daily doses of other statin types. A recent clinical record of myalgia was associated with an increased OR of 4(+) x ULN CPK (OR 1.73, 95% CI 1.37-2.18). In patients who were rechallenged to statins and had repeat CPK measurements after 4(+) x ULN CPK abnormalities, 54.8% of the repeat CPK values were within normal range, 32.1% between 1-3x and 13.0% 4(+) x ULN. CONCLUSIONS The frequencies of substantive CPK increases and rhabdomyolysis during statin treatment were low, with highest risks seen in those on large daily doses or interacting drugs and on rosuvastatin. CPK measurements appeared to have been done in a haphazard manner, and better guidance is needed.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 24602118
Web of Science ID: 340894300020
URI: http://researchonline.lshtm.ac.uk/id/eprint/1603996

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