Safety of atorvastatin in Asian patients within clinical trials

Abstract

Introduction: Data on statin safety in Asian patients are limited compared with evidence from Western populations.

Aim: This study assessed atorvastatin safety among Asian patients enrolled in 58 randomized clinical trials.

Methods: Data from 52 short-term trials (median exposure 4-72 weeks) and six long-term cardiovascular outcomes trials (median exposure 3.1-4.9 years) conducted across the atorvastatin 10-80-mg dose range were analyzed retrospectively to assess the incidence of safety endpoints.

Results: A total of 77 952 patients were identified (49 974 received atorvastatin), among whom 3191 were Asian (2519 received atorvastatin). In the short-term trials, the incidence of all-causality adverse events (AEs) and serious AEs (SAEs) in Asian patients treated with atorvastatin was similar to or lower than that observed with other statins or placebo, and discontinuations due to treatment-related AEs/SAEs were infrequent (2.0% across all doses). These observations were confirmed in the long-term trials. Treatment-related SAEs were rare (n = 4) among Asian patients receiving atorvastatin. No cases of rhabdomyolysis were observed in atorvastatin-treated Asian patients, and the incidence of myalgia was 1.8% in the short-term studies and 6.7% in the long-term trials. Elevations (>3× the upper limit of normal) in liver transaminases were observed in ~2% of Asian patients receiving atorvastatin; renal AEs occurred in <2%.

Conclusion: The incidence of AEs/SAEs with atorvastatin 10-40-mg in patients of Asian origin was low and comparable to placebo. Further evaluation of atorvastatin 80-mg is required owing to the limited number of Asian patients (n = 281; 11.2%) who received this dose.

Keywords: Adverse event; Asian; Atorvastatin; Cardiovascular disease; Data pooling; Hyperlipidemia.

Figure 1

Identification of Asian patients in randomized clinical trials of atorvastatin. Details of the long‐term CV outcomes trials are provided in the footnote to Table 1. CV, cardiovascular

Figure 2

Proportion of atorvastatin‐treated Asian patients experiencing musculoskeletal (A), hepatic (B), and renal (C) AEs. No musculoskeletal AE data were available for ASCOT‐LLA; hence, the long‐term trials included ASPEN, CARDS, SPARCL, IDEAL, and TNT. AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; CK, creatine kinase; ULN, upper limit of normal