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Predictors and outcomes of increases in creatine phosphokinase concentrations or rhabdomyolysis risk during statin treatment
Author(s) -
Staa Tjeerd P.,
Carr Daniel F.,
O'Meara Helen,
McCann Gerry,
Pirmohamed Munir
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12367
Subject(s) - rhabdomyolysis , medicine , statin , creatine kinase , myalgia , rosuvastatin , atorvastatin , concomitant , cohort , odds ratio , simvastatin , retrospective cohort study
Aim The aim was to evaluate clinical risk factors associated with myotoxicity in statin users. Methods This was a 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 ) concentrations and clinical records of rhabdomyolysis. Results The cohort comprised 641 703 statin users. Simvastatin was most frequently prescribed (66.3%), followed by atorvastatin (24.4%). CPK was measured in 127 209 patients: 81.4% within normal range and 0.7% above four times ULN CPK compared with normal CPK ( OR 1.28, 95% CI 1.01, 1.60). Rosuvastatin users had higher risk of >four times 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 >four times ULN CPK ( OR 1.73, 95% CI 1.37, 2.18). In patients who were rechallenged to statins and had repeat CPK measurements after >four times ULN CPK abnormalities, 54.8% of the repeat CPK values were within normal range, 32.1% between one to three times and 13.0% >four times 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.