Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial.

MedStar author(s):
Citation: American Journal of Cardiovascular Drugs. 16(1):55-65, 2016 Feb.PMID: 26385396Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Clinical Trial, Phase II | Journal Article | Multicenter Study | Randomized Controlled TrialSubject headings: *Coronary Artery Disease/dt [Drug Therapy] | *Plaque, Atherosclerotic/dt [Drug Therapy] | *Quinazolines/tu [Therapeutic Use] | Aged | Apolipoprotein A-I/me [Metabolism] | Cholesterol, HDL/bl [Blood] | Cholesterol, LDL/bl [Blood] | Coronary Angiography | Coronary Artery Disease/pp [Physiopathology] | Disease Progression | Double-Blind Method | Female | Humans | Male | Middle Aged | Prospective Studies | Quinazolines/pd [Pharmacology]Year: 2016Local holdings: Available online from MWHC library: 2001 - 2009ISSN:
  • 1175-3277
Name of journal: American journal of cardiovascular drugs : drugs, devices, and other interventionsAbstract: 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.All authors: Ballantyne CM, Barter PJ, Borgman M, Brewer HB, Herrman JP, Hu B, Kastelein JJ, Kataoka Y, Merkely B, Nicholls SJ, Nissen SE, Puri R, Uno K, Wolski KFiscal year: 2016Digital Object Identifier: Date added to catalog: 2017-03-06
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 26385396 Available 26385396

Available online from MWHC library: 2001 - 2009

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.

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