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Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study

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Abstract

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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Acknowledgments

The authors thank Meera Kodukulla, PhD, CMPP, of Amgen Inc. and Laura Evans, PharmD, on behalf of Amgen Inc., for initial drafting and editorial support. The study was funded by Amgen, Inc.

Author information

Authors and Affiliations

  1. Preventive Cardiology and Rehabilitation, Cleveland Clinic, 9500 Euclid Ave. Desk JB1, Cleveland, OH, USA

    Leslie Cho

  2. Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave. Desk JB1, Cleveland, OH, USA

    Michael Rocco

  3. Wesley Medical Centre, 40 Chasely Street, Auchenflower, Brisbane, 4066, QLD, Australia

    David Colquhoun

  4. Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Building 65 Missenden Road, Camperdown, NSW, Australia

    David Sullivan

  5. Cardiometabolic Disorders, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, Box 1030, New York, NY, 10029, USA

    Robert S. Rosenson

  6. Amgen (Europe) GmbH, Dammstrasse 23, 6300, Zug, Switzerland

    Ricardo Dent

  7. Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320, USA

    Allen Xue, Rob Scott & Scott M. Wasserman

  8. Department of Vascular Medicine, F4.211, Academic Medical Center, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands

    Erik Stroes

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Corresponding author

Correspondence to Leslie Cho.

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Disclosures

Dr. Cho has received research funding and consulting fees from Amgen Inc.

Dr. Rocco has received research funding from Amgen Inc., Pfizer and Eli Lilly, and consulting fees from Regeneron.

Dr. Colquhoun has received research funding from Amgen Inc, AstraZeneca, Abbott, Sanofi, and Pfizer pharmaceuticals. Dr. Colquhoun has served on advisory boards for Abbott, Merck Sharpe & Dohme, Pfizer, and Amgen Inc.

Dr. Sullivan reports receiving research funding from Amgen Inc, Abbott Products, AstraZeneca, Merck Sharp and Dohme, and Sanofi; educational program funding from Abbott Products, AstraZeneca, Merck Sharp and Dohme, Pfizer Australia, and Roche; and travel support from Merck Sharp and Dohme. Dr. Sullivan has served on advisory boards for Abbott Products, Merck Sharp and Dohme, and Pfizer Australia.

Dr. Rosenson has participated on advisory boards for Aegerion, Amgen Inc, Astra Zeneca, CVS Caremark, Novartis, Regeneron, and Sanofi. Dr. Rosenson has received institutional research grants from Amgen Inc, Astra Zeneca, and Sanofi and royalties from UpToDate, Inc.

Dr. Stroes reports receiving (non-substantial) lecturing fees from Aegerion, Amgen Inc, Merck, Novartis, Regeneron, and Sanofi.

Drs. Dent, Xue, Scott, and Wasserman are employees and stockholders of Amgen Inc.

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Cho, L., Rocco, M., Colquhoun, D. et al. Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study. Cardiovasc Drugs Ther 30, 297–304 (2016). https://doi.org/10.1007/s10557-016-6655-4

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