Evidence Table 11Studies on harms of statins in children

Author, yearHow adverse events assessedAdverse events reported
Clauss, 2005Clinical reviewLovastatin vs placebo (no significant differences):
Any clinical AE: 66% vs 68%
Treatment-related clinical AE: 9% vs 5%
No serious clinical AE, treatment related AE, discontinuations due to AE, CK greater than 10 times ULN, or ALT and/or AST greater than 3 times ULN
deJongh, 2002 ('Efficacy and safety…')Laboratory tests, otherwise not specified.
Prespecified adverse experiences were compared between treatment groups.
Simvastatin vs placebo at 48 weeks (no significant differences):
Drug-related clinical AE: 4.7% vs 3.4%
Drug-related laboratory AE: 1.2% vs 1.7%
No serious AE
deJongh, 2002 ('Early statin therapy…')Safety measurements including ALT, AST, and CK were measured during each visit.No significant differences with regard to safety measurements between simvastatin and placebo groups and no adverse events were reported.
Knipscheer, 1996Adverse events and vital signs recorded by physicians unaware of treatment allocation; laboratory safety parameters (routine hematology, biochemistry, and urinalysis).Adverse events equally distributed among treatment groups. No changes in laboratory safety measurement, including plasma TSH, ACTH, cortisol, creatine phosphokinasae, and liver enzyme levels, in any group from baseline to end of treatment period.
Marais, 2008Review of all safety parameters, including adverse events, clinical laboratory evaluations including regular assessments of liver transaminases and serum creatine kinase, vital signs, EKG, and physical examinations.Atorvastatin vs rosuvastatin (crossover comparison):
All AE: 15.8% vs 39.5%
Serious AE: 0 vs 5.3%
Treatment-related AE: 2.6% vs 0
No elevations of CK >10 times ULN

During first 18 weeks (rosuvastatin 20/40/80 mg):
All AE: 65.9%
Serious AE: 9.1%
Treatment-related AE: 18.2%
McCrindle, 2003AE reported by the subject or investigator were recorded at each study visit and for up Safety laboratories including AST, ALT, and CPK, were performed at weeks 4, 8, 18, and 39. Blood pressure and pulse measured at each study visit, and a full physical exam at screening and weeks 12, 16, and 52.Atorvastatin vs placebo:
AE: 62.9% vs 61.7%
Treatment-related Aes: 7% vs 4% (p=0.70)
Laboratory abnormalities: 29% vs 34%
One discontinuation in atorva group due to increased depression. No clinically relevant changes in vital signs noted in either group.
Stein, 1999Laboratory measurements including ALT, AST, and CK. Sexual maturation evaluated by Tanner staging.Lovastatin had no significant effect on growth parameters at 24 and 48 weeks.
More advanced Tanner staging and lager testicular volumes in lovastatin group, but not significantly different from placebo (p=0.85 and 0.33 for 24 and 48 weeks). Increase from baseline in ALT in both groups, no significant difference between groups (p=0.20).
No consistent changes in AST or CK. No clinically significant increase in transaminaes levels (>3 times ULN) or CK level (>10 times ULN). No differences between groups in clinical adverse events.
van der Graaf, 2008Physical examination, EKG, assessment of sexual maturation and growth, monitoring of menstrual periods fo female subjects, adverse event reports, and laboratory assessments.Treatment-emergent AE at 33 weeks, ezetimibe + simva vs simva:
Any AE: 83% vs 84%
ALT increased: 5% vs 2%
CPK elevation >10 times ULN: 1.6% vs 0
Myalgia: 6% vs 1%
No clinically significant adverse effects on growth, sexual maturation, or steroid hormones.
Wiegman, 2004Measured levels of sex steroids, gonadotopins, and variables of the pituitary-adrenal axis at baseline and at 1 and 2 years. Measurements of height, weight, body surface area, Tanner staging, and menarche or testicular volume. BMI, school records for education level and yearly progress, ALT, AST, adn CPK assessed at same time as lipids.No significant differences between pravastatin and placebo in change from baseline in physical characteristics, liver and muscle enzymes, or hormones; no effect of pravastatin on academic performance.

From: Evidence Tables

Cover of Drug Class Review: HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin
Drug Class Review: HMG-CoA Reductase Inhibitors (Statins) and Fixed-dose Combination Products Containing a Statin: Final Report Update 5 [Internet].
Smith MEB, Lee NJ, Haney E, et al.
Portland (OR): Oregon Health & Science University; 2009 Nov.
Copyright © 2009, Oregon Health & Science University, Portland, Oregon.

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