PCSK9 inhibitor effective in patients with statin intolerance

Comparison of PCSK9 Inhibitor Evolocumab Versus Ezetimibe in Statin-intolerant Patients: The Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects 3 (GAUSS-3) Trial

News - Apr. 3, 2016

Steven Nissen (Cleveland Clinic, Cleveland, OH, USA)

Presented at ACC 2016


Administration of statins to reduce LDL-C is an essential strategy to reduce morbidity and mortality  from atherosclerotic vascular disease. However, 5-10% of patients with high CV risk decline (or are reluctant) to take statins after experiencing muscle-related symptoms, creating an unmet clinical need. Diagnosis is primarily based on subjective patient complaints, since most patients do not have elevations in CK enzymes. Conflicting rates of muscle-related symptoms in observational studies and randomized trials raise questions about the true incidence of statin intolerance.
The Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects-3 (GAUSS-3) trial was designed in order to confirm statin-induced muscle intolerance via a blinded, placebo-controlled atorvastatin re-challenge and then to compare two alternative therapies, ezetimibe vs. evolocumab. The GAUSS-3 study enrolled 511 patients at 53 health care centers. A majority of randomized patients had high cardiovascular risk and 82% failed 3 or more statins. Median baseline LDL-C was 212 mg/dL, median age was 61 years with nearly equal numbers of men and women, and 1/3 had coronary disease.

Main results

  • 42.6% of 491 patients who had previously reported muscle pain with at least two different statins had a recurrence of symptoms during blinded administration of atorvastatin, but not while taking a placebo.
  • After a 24-week treatment period, patients with confirmed statin intolerance who were given evolocumab on average showed a 52.8% reduction in LDL cholesterol (one of the study’s co-primary endpoints) compared with a 16.7% reduction for patients taking ezetimibe (P<0.001).
  • The average change in LDL cholesterol for weeks 22 and 24 (the other co-primary endpoint), patients taking evolocumab showed a reduction of 54.5% and patients taking ezetimibe showed a reduction of 16.7% (P<0.001).
  • Both drugs uncommonly induced muscle symptoms leading to discontinuation (ezetimibe 6.8%, evolocumab 0.7%).  


The GAUSS-3 trial demonstrates that in patients with statin-induced muscle-related adverse events, the use of evolocumab resulted in a significantly greater reduction in LDL-C levels after 24 weeks, compared with ezetimibe. Further studies are necessary to assess long-term efficacy and safety.


Press release ACC 2016, 3 April 2016

This study was published simultaneously in JAMA

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