TY  - BOOK
AU  - Brewer, H Bryan
TI  - Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial
SN  - 1175-3277
KW  - *Coronary Artery Disease/dt [Drug Therapy]
KW  - *Plaque, Atherosclerotic/dt [Drug Therapy]
KW  - *Quinazolines/tu [Therapeutic Use]
KW  - Aged
KW  - Apolipoprotein A-I/me [Metabolism]
KW  - Cholesterol, HDL/bl [Blood]
KW  - Cholesterol, LDL/bl [Blood]
KW  - Coronary Angiography
KW  - Coronary Artery Disease/pp [Physiopathology]
KW  - Disease Progression
KW  - Double-Blind Method
KW  - Female
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Prospective Studies
KW  - Quinazolines/pd [Pharmacology]
KW  - MedStar Health Research Institute
KW  - Clinical Trial, Phase II
KW  - Journal Article
KW  - Multicenter Study
KW  - Randomized Controlled Trial
N1  - Available online from MWHC library: 2001 - 2009
N2  - BACKGROUND: Bromodomain and extra-terminal (BET) proteins regulate transcription of lipoprotein and inflammatory factors implicated in atherosclerosis. The impact of BET inhibition on atherosclerosis progression is unknown; CONCLUSION: Administration of the BET protein inhibitor RVX-208 showed no greater increase in apoA-I or HDL-C or incremental regression of atherosclerosis than administration of placebo; METHODS: ASSURE was a double-blind, randomized, multicenter trial in which 323 patients with angiographic coronary disease and low high-density lipoprotein cholesterol (HDL-C) levels were randomized in a 3:1 fashion to treatment with the BET protein inhibitor RVX-208 200 mg or placebo for 26 weeks. Plaque progression was measured with serial intravascular ultrasound imaging. Lipid levels, safety, and tolerability were also assessed; RESULTS: During treatment, apolipoprotein (apo)A-I increased by 10.6% with placebo (P < 0.001 compared with baseline) and 12.8% with RVX-208 (P < 0.001 compared with baseline), between groups P = 0.18. HDL-C increased by 9.1% with placebo (P < 0.001 compared with baseline) and 11.1% with RVX-208 (P < 0.001 compared with baseline), between groups P = 0.24. Low-density lipoprotein cholesterol (LDL-C) decreased by 17.9% with placebo (P < 0.001 compared with baseline) and 15.8% with RVX-208 (P < 0.001 compared with baseline), between groups P = 0.55. The primary endpoint, the change in percent atheroma volume, decreased 0.30% in placebo-treated patients (P = 0.23 compared with baseline) and 0.40% in the RVX-208 group (P = 0.08 compared with baseline), between groups P = 0.81. Total atheroma volume decreased 3.8 mm(3) in the placebo group (P = 0.01 compared with baseline) and 4.2 mm(3) in the RVX-208 group (P < 0.001 compared with baseline), P = 0.86 between groups. A greater incidence of elevated liver enzymes was observed in RVX-208-treated patients (7.1 vs. 0%, P = 0.009); TRIAL REGISTRATION: ClinicalTrials.gov identifier-NCT01067820
UR  - http://dx.doi.org/10.1007/s40256-015-0146-z
ER  -