Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial

Journal article

Importance: Muscle-related statin intolerance is reported by 5% to 20% of patients.
Objective: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab.
Design, Setting, and Participants: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks.
Interventions: Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily).
Main Outcome and Measures: Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels.
Conclusions and Relevance: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety.
Trial Registration: clinicaltrials.gov Identifier: NCT01984424

Authors: Preiss, D; GAUSS-3 Investigators

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Medical Association
• Journal: Journal of the American Medical Association
• Publication date: 2016-04-03
• Acceptance date: 2016-03-10
• DOI: 10.1001/jama.2016.3608
• EISSN: 1538-3598
• ISSN: 0098-7484