Impact of statin dosing intensity on transaminase and creatine kinase.
OBJECTIVE
Higher intensity statin therapy reduces cardiovascular events more than lower intensity therapy, but the safety impact of higher intensity therapy is unknown. We performed a meta-analysis of randomized controlled trials comparing higher versus lower intensity therapy on liver and muscle safety.


METHODS
A systematic literature search through January 2006 was conducted to identify randomized trials comparing higher versus lower intensity statin therapy meeting our criteria. Weighted averages were reported as relative risks (RRs) with 95% confidence intervals (random-effects model). Statistical heterogeneity scores were assessed with the Q statistic and L'Abbe plots. Publication bias was assessed with the Egger weighted regression and funnel plots.


RESULTS
Higher intensity statin therapy increased the incidence of transaminase elevations (RR 3.10 [95% Confidence Interval [CI], 0.88-7.85]) versus lower intensity statin therapy. 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, 1.83-6.85]), but higher intensity lipophilic therapy did not (RR 1.58 [95% CI, 0.81-3.08]). 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, 1.36-27.35]).


CONCLUSIONS
More aggressive statin therapy increases the incidence of transaminase elevations in clinical trials versus lower intensity therapy. Increases in transaminases may be more problematic when hydrophilic statins are used aggressively, whereas CK elevations are more problematic with higher intensity lipophilic statin therapy.
Dale
Krista M
KM
The University of Connecticut Schools of Pharmacy, Hartford, Conn 06102-5037, USA.
White
C Michael
CM
Henyan
Nickole N
NN
Kluger
Jeffrey
J
Coleman
Craig I
CI
D000069059:Atorvastatin; D003402:Creatine Kinase / Q000097:blood*; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008111:Liver Function Tests; D008148:Lovastatin / Q000008:administration & dosage; D017035:Pravastatin / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000008:administration & dosage; D000637:Transaminases / Q000097:blood*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D000637:Transaminases; D003402:Creatine Kinase; D017035:Pravastatin