Anti-PCSK9 Antibody Effectively Lowers Cholesterol in Patients With Statin Intolerance: The GAUSS-2 Randomized, Placebo-Controlled Phase 3 Clinical Trial of Evolocumab

Study Questions:

What is the efficacy and safety of subcutaneous (SC) evolocumab compared with oral ezetimibe in hypercholesterolemic subjects unable to tolerate effective statin doses?


The GAUSS-2 (Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects) was a 12-week, double-blind study, which randomized patients (2:2:1:1) to evolocumab 140 mg biweekly (Q2W) or evolocumab 420 mg monthly (QM) both with daily oral placebo (PBO); or SC PBO Q2W or QM both with daily oral ezetimibe 10 mg. Coprimary endpoints were percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12 and at the mean of weeks 10 and 12.


A total of 307 patients (mean [standard deviation] age 62 [10], LDL-C 193 [59] mg/dl) were randomized. Evolocumab reduced LDL-C from baseline by 53-56%, corresponding to treatment differences versus ezetimibe of 37-39% (p < 0.001). Muscle adverse events occurred in 12% of evolocumab- and 23% of ezetimibe-treated patients. Treatment-emergent adverse events and laboratory abnormalities were comparable across treatment groups.


The authors concluded that efficacy combined with favorable tolerability makes evolocumab a promising therapy for high-risk patients with elevated cholesterol who are statin intolerant.


In this study, evolocumab administered over 3 months yielded a significant reduction in LDL-C in hypercholesterolemic patients unable to tolerate effective doses of at least two statins, reflecting a population with a true unmet need. The low incidence of muscle-related side effects in this report underscores evolocumab as a useful therapy for hypercholesterolemic patients who presently have few tolerable treatment options, provided that clinical benefit is confirmed in ongoing endpoint trials such as the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial.

Keywords: Proprotein Convertases, Cholesterol, Dyslipidemias, Azetidines, Cardiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Receptors, LDL, Hypercholesterolemia, Pregnancy, ACC Annual Scientific Session

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