Safety profile of statins alone or combined with ezetimibe: a pooled analysis of 27 studies including over 22,000 patients treated for 624weeks
International Journal of Clinical Practice, 07/24/2012
Toth PP et al. – 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.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.
- 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.