Comparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial
Statins are the accepted standard for lowering low-density lipoprotein-cholesterol (LDLC). However, 5%-10% of statin-treated patients report intolerance, mostly due to musclerelated adverse effects. There are challenges to objective identification of patients with statin intolerance. Evolocumab is a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Sprog: | English |
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Wiley
2016
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| _version_ | 1826314873940738048 |
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| author | Nissen, SE Dent-Acosta, RE Rosenson, RS Stroes, E Sattar, N Mancini, GBJ Ballantyne, CM Catapano, A Gouni-Berthold, I Stein, EA Xue, A Wasserman, SM Scott, R Preiss, D Thompson, PD |
| author_facet | Nissen, SE Dent-Acosta, RE Rosenson, RS Stroes, E Sattar, N Mancini, GBJ Ballantyne, CM Catapano, A Gouni-Berthold, I Stein, EA Xue, A Wasserman, SM Scott, R Preiss, D Thompson, PD |
| author_sort | Nissen, SE |
| collection | OXFORD |
| description | Statins are the accepted standard for lowering low-density lipoprotein-cholesterol (LDLC). However, 5%-10% of statin-treated patients report intolerance, mostly due to musclerelated adverse effects. There are challenges to objective identification of patients with statin intolerance. Evolocumab is a monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in marked LDL-C reduction. We report the design of Goal Achievement after Utilizing an anti-PCSK9 Antibody in Statin Intolerant Subjects 3 (GAUSS-3), a phase 3, multicenter, randomized, double-blind, ezetimibe-controlled study to compare the effectiveness of 24 weeks of evolocumab 420 mg monthly versus ezetimibe 10 mg/day in hypercholesterolemic patients unable to tolerate an effective statin dose. The study incorporates a novel atorvastatin-controlled, double-blind, cross-over phase intended to objectively identify statin intolerance. Eligible patients had LDL-C above the National Cholesterol Education Project Adult Treatment Panel III target level for the appropriate coronary heart disease risk category and were unable to tolerate at least 3 statins or 2 statins (one of which was atorvastatin ≤10 mg/day) or had a history of marked CK elevation accompanied by muscle symptoms while on one statin. This trial has two co-primary endpoints: mean percent change from baseline in LDL-C at Weeks 22 and 24 and percent change from baseline in LDL-C at Week 24. Key secondary efficacy endpoints include change from baseline in LDL-C; percent of patients attaining an LDL-C <70 mg/dL [1.81 mmol/L]); and percent change from baseline in total cholesterol, non-HDL-C, and ApoB. Recruitment of 511 patients was completed on November 28, 2014. |
| first_indexed | 2024-03-07T05:30:53Z |
| format | Journal article |
| id | oxford-uuid:e23b5e3f-db8d-480b-9893-c494bac0bd43 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:12:32Z |
| publishDate | 2016 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:e23b5e3f-db8d-480b-9893-c494bac0bd432024-10-15T11:28:20ZComparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e23b5e3f-db8d-480b-9893-c494bac0bd43EnglishSymplectic Elements at OxfordWiley2016Nissen, SEDent-Acosta, RERosenson, RSStroes, ESattar, NMancini, GBJBallantyne, CMCatapano, AGouni-Berthold, IStein, EAXue, AWasserman, SMScott, RPreiss, DThompson, PDStatins are the accepted standard for lowering low-density lipoprotein-cholesterol (LDLC). However, 5%-10% of statin-treated patients report intolerance, mostly due to musclerelated adverse effects. There are challenges to objective identification of patients with statin intolerance. Evolocumab is a monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in marked LDL-C reduction. We report the design of Goal Achievement after Utilizing an anti-PCSK9 Antibody in Statin Intolerant Subjects 3 (GAUSS-3), a phase 3, multicenter, randomized, double-blind, ezetimibe-controlled study to compare the effectiveness of 24 weeks of evolocumab 420 mg monthly versus ezetimibe 10 mg/day in hypercholesterolemic patients unable to tolerate an effective statin dose. The study incorporates a novel atorvastatin-controlled, double-blind, cross-over phase intended to objectively identify statin intolerance. Eligible patients had LDL-C above the National Cholesterol Education Project Adult Treatment Panel III target level for the appropriate coronary heart disease risk category and were unable to tolerate at least 3 statins or 2 statins (one of which was atorvastatin ≤10 mg/day) or had a history of marked CK elevation accompanied by muscle symptoms while on one statin. This trial has two co-primary endpoints: mean percent change from baseline in LDL-C at Weeks 22 and 24 and percent change from baseline in LDL-C at Week 24. Key secondary efficacy endpoints include change from baseline in LDL-C; percent of patients attaining an LDL-C <70 mg/dL [1.81 mmol/L]); and percent change from baseline in total cholesterol, non-HDL-C, and ApoB. Recruitment of 511 patients was completed on November 28, 2014. |
| spellingShingle | Nissen, SE Dent-Acosta, RE Rosenson, RS Stroes, E Sattar, N Mancini, GBJ Ballantyne, CM Catapano, A Gouni-Berthold, I Stein, EA Xue, A Wasserman, SM Scott, R Preiss, D Thompson, PD Comparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial |
| title | Comparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial |
| title_full | Comparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial |
| title_fullStr | Comparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial |
| title_full_unstemmed | Comparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial |
| title_short | Comparison of PCSK9 inhibitor evolocumab vs ezetimibe in statin-intolerant patients: Design of the goal achievement after utilizing an anti-PCSK9 antibody in statin-intolerant subjects 3 (GAUSS-3) trial |
| title_sort | comparison of pcsk9 inhibitor evolocumab vs ezetimibe in statin intolerant patients design of the goal achievement after utilizing an anti pcsk9 antibody in statin intolerant subjects 3 gauss 3 trial |
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