Abstract | BACKGROUND: METHODS AND RESULTS: This double-blind, placebo-controlled, phase 3 trial randomized patients with HeFH and coronary artery disease on maximally tolerated statin and LDL-C ≥2.6 mmol/L (≥100 mg/dL) to weekly subcutaneous mipomersen 200 mg or placebo (2:1) for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28. Safety assessments included adverse events, laboratory tests, and magnetic resonance imaging assessment of hepatic fat. Of 124 randomized patients (41 placebo, 83 mipomersen), 114 (41 placebo, 73 mipomersen) completed treatment. Mean (95% confidence interval) LDL-C decreased significantly with mipomersen (-28.0% [-34.0% to -22.1%] compared with 5.2% [-0.5% to 10.9%] increase with placebo; P<0.001). Mipomersen significantly reduced apolipoprotein B (-26.3%), total cholesterol (-19.4%), and lipoprotein(a) (-21.1%) compared with placebo (all P<0.001). No significant change occurred in high-density lipoprotein cholesterol. Adverse events included injection site reactions and influenza-like symptoms. Five mipomersen patients (6%) had 2 consecutive alanine aminotransferase values ≥3 times the upper limit of normal at least 7 days apart; none were associated with significant bilirubin increases. Hepatic fat content increased a median of 4.9% with mipomersen versus 0.4% with placebo (P<0.001). CONCLUSIONS: CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00706849.
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Authors | Evan A Stein, Robert Dufour, Claude Gagne, Daniel Gaudet, Cara East, Joanne M Donovan, Wai Chin, Diane L Tribble, Mary McGowan |
Journal | Circulation
(Circulation)
Vol. 126
Issue 19
Pg. 2283-92
(Nov 06 2012)
ISSN: 1524-4539 [Electronic] United States |
PMID | 23060426
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticholesteremic Agents
- Apolipoproteins B
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Oligonucleotides
- Oligonucleotides, Antisense
- mipomersen
- Alanine Transaminase
- Bilirubin
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Topics |
- Alanine Transaminase
(metabolism)
- Anticholesteremic Agents
(therapeutic use)
- Apolipoproteins B
(antagonists & inhibitors)
- Bilirubin
(metabolism)
- Comorbidity
- Coronary Artery Disease
(drug therapy, epidemiology, metabolism)
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Heterozygote
- Humans
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(therapeutic use)
- Hyperlipoproteinemia Type II
(drug therapy, epidemiology, metabolism)
- Injections, Subcutaneous
- Liver
(metabolism, pathology)
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Oligonucleotides
(administration & dosage, adverse effects, therapeutic use)
- Oligonucleotides, Antisense
(administration & dosage, adverse effects, therapeutic use)
- Treatment Outcome
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