{"id":"6bb3bbb36119","type":"article","url":"https://hartvaat.nl/2016/04/19/evolocumab-versus-ezetimibe-bij-statine-intolerante-patienten-de-gauss-3-trial/","title":"Evolocumab versus ezetimibe bij statine-intolerante patiënten: de GAUSS-3-trial","title_en":"Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","huisarts","internist"],"tags":["clear-outcomes","niet-statine-therapie","statines"],"journal":"JAMA","doi":"10.1001/jama.2016.3608","source_url":"https://doi.org/10.1001/jama.2016.3608","authors":["Steven E Nissen","Erik Stroes","Ricardo E Dent-Acosta","Robert S Rosenson","Sam J Lehman","Naveed Sattar","David Preiss","Eric Bruckert","Richard Ceška","Norman Lepor","Christie M Ballantyne","Ioanna Gouni-Berthold","Mary Elliott","Danielle M Brennan","Scott M Wasserman","Ransi Somaratne","Rob Scott","Evan A Stein"],"significance":8,"published":"2016-04-19","source_date":"2016-04-19","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/","https://hartvaat.nl/kennis/lipiden/ezetimib/"],"congress":"","summary_en":"The GAUSS-3 trial demonstrated that evolocumab was significantly more effective than ezetimibe for LDL cholesterol lowering in patients with confirmed statin-associated muscle symptoms, without causing similar muscle-related adverse events. The study established PCSK9 inhibitors as an effective option for statin-intolerant patients.","created":"2026-07-03T10:26:03Z","updated":"2026-07-03T13:25:24Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"JAMA-trial die evolocumab vergeleek met ezetimibe bij patiënten met spiergerelateerde statine-intolerantie. Eerste head-to-head vergelijking van een PCSK9-remmer met ezetimibe in deze specifieke patiëntengroep.","abstract_original":"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. RESULTS: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). 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). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8 mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptoms were 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%). 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."}