Aims: The aim of this analysis was to assess the overall safety and tolerability profiles of various statins + ezetimibe vs. statin monotherapy and to explore tolerability in sub-populations grouped by age, race, and sex. Methods: Study-level data were combined from 27 double-blind, placebo-controlled or active-comparator trials that randomized adult hypercholesterolemic patients to statin or statin + ezetimibe for 6-24 weeks. In the full cohort, % patients with AEs within treatment groups (statin: N = 10,517; statin + ezetimibe: N = 11,714) was assessed by logistic regression with terms for first-/second-line therapy (first line = drug-naïve or rendered drug-naïve by washout at study entry; second line = ongoing statin at study entry or statin run-in), trial within first-/second-line therapy, and treatment. The same model was fitted for age (< 65, ≥ 65 years), sex, race (white, black, other) and first-/second-line subgroups with additional terms for subgroup and subgroup-by-treatment interaction. Results: In the full cohort, the only significant difference between treatments was consecutive AST or ALT elevations ≥ 3 × upper limit of normal (ULN) (statin: 0.35%, statin + ezetimibe: 0.56%; p = 0.017). Significantly more subjects reported ≥ 1 AE; drug-related, hepatitis-related and gastrointestinal-related AEs; and CK elevations ≥ 10 × ULN (all p ≤ 0.008) in first-line vs. second-line therapy studies with both treatments. AEs were generally similar between treatments in subgroups, and similar rates of AEs were reported within age and race subgroups; however, women reported generally higher AE rates. Conclusions: In conclusion, in second-line studies, ongoing statin treatment at study entry likely screened out participants for previous statin-related AEs and tolerability issues. These results describe the safety profiles of widely used lipid-lowering therapies and encourage their appropriate and judicious use in certain subpopulations.
© 2012 Blackwell Publishing Ltd.