Clinical profile of statin intolerance in the phase 3 GAUSS-2 Study
Open accessAbstract
Purpose Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905).Methods GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS.Results Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion.Conclusion Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.
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In the SEAS and SHARP trials, a reduction in cardiovascular events was demonstrated in the simvastatin-ezetimibe arm versus placebo.
“In both the SEAS and SHARP trials, a reduction in CV events was demonstrated in the simvastatin-ezetimibe arm vs. placebo [266,267].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [267]
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2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
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- Authors
- Cho, L., Rocco, M., Colquhoun, D., Sullivan, D., Rosenson, R. S., Dent, R., Xue, A., Scott, R., Wasserman, S. M., & Stroes, E.
- Affiliations
- Cleveland Clinic (US)
- Wesley Hospital (AU)
- Royal Prince Alfred Hospital (AU)
- Icahn School of Medicine at Mount Sinai (US)
- Amgen (Switzerland) (CH)
- Amgen (United States) (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Cho, Leslie
- Venue
- Cardiovascular Drugs and Therapy
- Published
- 2016-03-02
- Volume
- 30
- Issue
- 3
- Pages
- 297-304
- ISSN
- 0920-3206 (ISSN-L)
- 1573-7241
- OpenAlex
- W2288476146
- Cited by
- 30
- References
- 47
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Cardiovascular Drugs and Therapy (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Amgen
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Keywords
- statin intolerance, statin-associated muscle symptoms, evolocumab, ezetimibe, PCSK9 inhibition, hypercholesterolemia, LDL cholesterol, myalgia, quality of life, statin discontinuation
- MeSH terms
- Ezetimibe, Proprotein Convertase 9, PCSK9 Inhibitors, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Anticholesteremic Agents, Double-Blind Method, Female, Humans, Hypercholesterolemia, Cholesterol, LDL, Male, Middle Aged, Muscular Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Young Adult, Antibodies, Monoclonal, Humanized
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