Lipid-efficacy RCT · JAMA 2016
GAUSS-3 trial
Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial.
The bottom line
In statin-intolerant patients, evolocumab produced substantially greater LDL-C lowering than ezetimibe over 24 weeks, with fewer treatment discontinuations for muscle symptoms.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Subcutaneous evolocumab 420 mg monthly (n=145)
- Compared with
- Oral ezetimibe 10 mg daily (n=73)
- People
- 218
- Who took part
- Adult patients with uncontrolled LDL-C levels and history of intolerance to 2 or more statins, with muscle symptoms confirmed by statin rechallenge (or elevated creatine kinase)
- Design
- Two-stage randomized clinical trial; Phase A: crossover with atorvastatin vs placebo; Phase B: randomized (2:1) to evolocumab or ezetimibe
- Follow-up
- 24 weeks
- Main question
- 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
Main result
For the mean of weeks 22 and 24, mean percent LDL-C change was -16.7% (95% CI, -20.5% to -12.9%) with ezetimibe vs -54.5% (95% CI, -57.2% to -51.8%) with evolocumab (P < .001); between-group difference -37.8%. At week 24, mean percent change was -16.7% (95% CI, -20.8% to -12.5%) with ezetimibe vs -52.8% (95% CI, -55.8% to -49.8%) with evolocumab (P < .001); between-group difference -36.1%.
Effect on LDL cholesterol
Ezetimibe: LDL-C 183.0 mg/dL at mean of weeks 22/24 (absolute change -31.0 mg/dL), 181.5 mg/dL at week 24 (absolute change -31.2 mg/dL). Evolocumab: LDL-C 103.6 mg/dL at mean of weeks 22/24 (absolute change -106.8 mg/dL), 104.1 mg/dL at week 24 (absolute change -102.9 mg/dL). Between-group absolute difference -75.8 mg/dL (mean of weeks 22/24) and -71.7 mg/dL (week 24).
Other results
Not reported
Safety
Muscle symptoms reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%).
In the trial's own words
“For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7% (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001).”
Quoted from the abstract of JAMA 2016, checked word for word against PubMed. PubMed 27039291 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Evolocumab (Repatha) and alirocumab (Praluent)
Common questions
What did the GAUSS-3 trial find?
In statin-intolerant patients, evolocumab produced substantially greater LDL-C lowering than ezetimibe over 24 weeks, with fewer treatment discontinuations for muscle symptoms.
Who was in GAUSS-3?
218 people. Adult patients with uncontrolled LDL-C levels and history of intolerance to 2 or more statins, with muscle symptoms confirmed by statin rechallenge (or elevated creatine kinase).
What was GAUSS-3's main result?
For the mean of weeks 22 and 24, mean percent LDL-C change was -16.7% (95% CI, -20.5% to -12.9%) with ezetimibe vs -54.5% (95% CI, -57.2% to -51.8%) with evolocumab (P < .001); between-group difference -37.8%. At week 24, mean percent change was -16.7% (95% CI, -20.8% to -12.5%) with ezetimibe vs -52.8% (95% CI, -55.8% to -49.8%) with evolocumab (P < .001); between-group difference -36.1%.
How much did LDL cholesterol change in GAUSS-3?
Ezetimibe: LDL-C 183.0 mg/dL at mean of weeks 22/24 (absolute change -31.0 mg/dL), 181.5 mg/dL at week 24 (absolute change -31.2 mg/dL). Evolocumab: LDL-C 103.6 mg/dL at mean of weeks 22/24 (absolute change -106.8 mg/dL), 104.1 mg/dL at week 24 (absolute change -102.9 mg/dL). Between-group absolute difference -75.8 mg/dL (mean of weeks 22/24) and -71.7 mg/dL (week 24).
Related trials
- GLAGOV (2016)Adding evolocumab to statin therapy in patients with coronary artery disease caused regression of coronary atherosclerosis on IVUS imaging compared with placebo, though its effect on clinical cardiovascular outcomes was not assessed in this trial.
- ODYSSEY ALTERNATIVE (2015)In statin-intolerant patients, alirocumab lowered LDL-C far more than ezetimibe and caused fewer muscle-related adverse events than statin rechallenge with atorvastatin.
- ODYSSEY FH I and II (2015)In patients with heterozygous familial hypercholesterolemia inadequately controlled on maximally tolerated lipid-lowering therapy, adding alirocumab produced large, durable LDL-C reductions through 78 weeks and was generally well tolerated.
- ODYSSEY LONG TERM (2015)Adding alirocumab to maximally tolerated statin therapy markedly lowered LDL cholesterol and was associated with a post hoc reduction in cardiovascular events, though with somewhat higher rates of injection-site reactions, myalgia, neurocognitive, and ophthalmologic events.
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