Statin intolerance due to muscle symptoms affects management of patients: insights from the CLEAR outcomes trial.

Abstract

Background: In CLEAR Outcomes the non-statin bempedoic acid (BA) 180 mg daily reduced MACE-4 (nonfatal MI, nonfatal stroke, coronary revascularization, or CV death) by 13% in 13970 patients at high CV risk with statin intolerance (SI) over a median of 40.6 months. This is the largest prospective database of patients with SI. Aim(s): To assess whether there were differences in SI symptom history and whether this influenced the clinical course during CLEAR Outcomes. Method(s): SI symptoms and impact on activities of daily living (ADL) were recorded prior to randomization. Patients were grouped post hoc as reporting only statin associated muscle symptoms (SAMS), only non-muscle adverse effects (NonSAMS), or BOTH. Result(s): At baseline 6887 (49.3%) patients reported SAMS, 2485 (18%) NonSAMS, and 4587 (33%) BOTH. SI symptoms had a moderate/severe impact on ADL in 62% SAMS, 48% NonSAMS, and 69% BOTH. Use of any lipid modifying treatment at baseline was 43% SAMS, 36% NonSAMS, and 42% BOTH. Compared to placebo, BA reduced LDL-C at 6 months by 21% in SAMS, 22% in NonSAMS, and 21% in BOTH. There was no difference in the effect on MACE-4 by SI group. New use of moderate/high intensity statin during the study was relatively infrequent (3.2-8.0%) but higher in PBO than BA in all SI groups and was not generally maintained at study end (Table 1). Muscle adverse events (AE) were more frequent and resulted in higher rates of treatment DC in SAMS/BOTH vs NonSAMS (Table 2). There was no difference between BA and PBO in the rate of muscle related AE. Conclusion(s): SAMS are the predominant cause of SI in patients in CLEAR Outcomes. Patients with a history of SAMS had higher rates of muscle AE and study drug DC due to muscle AE versus NonSAMS. Muscle AE rates and study drug DC were balanced between BA and PBO within each SI symptom subgroup. CLEAR Outcomes exhibits the challenges of treating patients with SI. These data also demonstrate that BA can be useful in reducing CV risk in this patient population.