A systematic review 1 including 9 studies with a total of 30 653 subjects was abstracted in DARE. The interventions in the included studies comprised atorvastatin, pravastatin, simvastatin and lovastatin, and the follow-up ranged from 1 to 5 years. The included studies defined elevated transaminases as more than two or three times the upper limit of normal, while CK elevations were defined as more than three times or more than ten times the upper limit of normal. Higher intensity statin therapy increased the incidence of transaminase elevations (RR 3.10, 95% CI 0.88 to 7.85) versus lower intensity statin therapy, although the difference was not statistically significant. When studies of hydrophilic and lipophilic statins were evaluated separately, higher intensity hydrophilic statin therapy increased the risk for transaminase elevations (RR 3.54, 95% CI 1.83 to 6.85), but higher intensity lipophilic therapy did not (RR 1.58, 95% CI 0.81 to 3.08). The risk of creatine kinase (CK) elevations showed a trend toward an increase (RR 2.63, 95% CI 0.88-7.85) with higher intensity therapy. No occurrences of CK elevations occurred in studies evaluating hydrophilic statins, whereas lipophilic statins showed an increased risk with higher intensity therapy (RR 6.09, 95% CI 1.36 to 27.35).
Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in interventions and outcomes) and by imprecise results (wide confidence intervals).
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