Abstract 17209: Impact of Female Sex on Discontinuation Rates and Creatine Kinase Elevations in Atorvastatin Trials
Objectives: We evaluated the impact of female sex on discontinuation rates and creatine kinase (CK) elevations in large clinical trials of atorvastatin (A).
Methods: In IDEAL (A 80 mg vs. simvastatin 20-40 mg), TNT (A 80 mg vs. A 10 mg), SPARCL (A 80 mg vs. placebo), CARDS, ASCOT, and ASPEN (A 10 mg vs. placebo in all 3 trials), the impact of female sex on therapy discontinuation rates due to adverse events (AEs) was studied using logistic regression performed on each study separately. Studies were not pooled since the doses and comparators were different in each trial. The impact of sex on CK elevations and myalgias by baseline CK was also determined in 5 of the studies.
Results: Discontinuation rates due to AEs were higher among women than men in IDEAL, TNT, SPARCL and ASCOT, while rates were similar in ASPEN and CARDS (see table). In the IDEAL study (which was unblinded), a significant treatment-gender interaction was present (P=0.010) and more women discontinued A therapy, mostly due to myalgias. In the other 5 trials, no significant interaction between A discontinuation and gender was seen, and the most frequent AEs in women were: liver function test abnormalities in SPARCL, pain in CARDS, and myalgias in ASCOT/ASPEN/TNT. Only 24/7080 (0.3%) women and 182/21255 (0.9%) men had CK elevations from baseline ≥ 3 x ULN. Among subjects with baseline CK < 3 x ULN, rates of myalgias were 714/7061 (10.1%) in women and 1775/ 21107 (8.4%) in men. In subjects with baseline CK ≥ 3 x ULN, 2/19 (10.5%) women and 14/148 (9.5%) men had treatment emergent myalgias.
Conclusions: While more discontinuations due to AEs occurred among women in 4/6 atorvastatin studies, the treatment-sex interaction was only significant in the IDEAL study, suggesting that atorvastatin may have a similar impact on discontinuations in both sexes. AEs associated with discontinuations in women as well as men included myalgias, liver function test abnormalities, and pain. Rates of CK elevations were low in both sexes.
- © 2013 by American Heart Association, Inc.