P P Toth1, D Morrone, W S Weintraub, M E Hanson, R S Lowe, J Lin, A K Shah, A M Tershakovec. 1. CGH Medical Center, Sterling, IL, and University of Illinois College of Medicine, Peoria, IL, USA Christiana Center for Outcomes Research, Christiana Care Health System, Newark, DE, USA Global Scientific and Medical Publications, Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA Project Leadership and Management, Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
Abstract
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.
RCT Entities:
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 hypercholesterolemicpatients 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.
Authors: Ange Wang; Marcia L Stefanick; Kristopher Kapphahn; Haley Hedlin; Manisha Desai; Jo Ann E Manson; Howard Strickler; Lisa Martin; Jean Wactawski-Wende; Michael Simon; Jean Y Tang Journal: Br J Cancer Date: 2016-01-07 Impact factor: 7.640