Abstract | OBJECTIVE: APPROACH AND RESULTS: In 4 phase III trials, 382 patients on maximally tolerated lipid-lowering therapy were randomized 2:1 to weekly subcutaneous mipomersen 200 mg (n=256) or placebo (n=126) for 26 weeks. Populations included homozygous FH, heterozygous FH with concomitant coronary artery disease (CAD), severe hypercholesterolemia, and hypercholesterolemia at high risk for CAD. Lp(a) was measured 8× between baseline and week 28 inclusive. Of the 382 patients, 57% and 44% had baseline Lp(a) levels >30 and >50 mg/dL, respectively. In the pooled analysis, the mean percent decrease (median, interquartile range in Lp(a) at 28 weeks was significantly greater in the mipomersen group compared with placebo (-26.4 [-42.8, -5.4] versus -0.0 [-10.7, 15.3]; P<0.001). In the mipomersen group in patients with Lp(a) levels >30 or >50 mg/dL, attainment of Lp(a) values ≤30 or ≤50 mg/dL was most frequent in homozygous FH and severe hypercholesterolemia patients. In the combined groups, modest correlations were present between percent change in apolipoprotein B-100 and Lp(a) (r=0.43; P<0.001) and low-density lipoprotein cholesterol and Lp(a) (r=0.36; P<0.001) plasma levels. CONCLUSIONS:
Mipomersen consistently and effectively reduced Lp(a) levels in patients with a variety of lipid abnormalities and cardiovascular risk. Modest correlations were present between apolipoprotein B-100 and Lp(a) lowering but the mechanistic relevance mediating Lp(a) reduction is currently unknown.
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Authors | Raul D Santos, Frederick J Raal, Alberico L Catapano, Joseph L Witztum, Elisabeth Steinhagen-Thiessen, Sotirios Tsimikas |
Journal | Arteriosclerosis, thrombosis, and vascular biology
(Arterioscler Thromb Vasc Biol)
Vol. 35
Issue 3
Pg. 689-99
(Mar 2015)
ISSN: 1524-4636 [Electronic] United States |
PMID | 25614280
(Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural)
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Copyright | © 2015 American Heart Association, Inc. |
Chemical References |
- APOB protein, human
- Anticholesteremic Agents
- Apolipoprotein B-100
- Biomarkers
- Lipoprotein(a)
- Oligodeoxyribonucleotides, Antisense
- Oligonucleotides
- mipomersen
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Topics |
- Adult
- Aged
- Anticholesteremic Agents
(therapeutic use)
- Apolipoprotein B-100
(blood, genetics)
- Biomarkers
(blood)
- Cardiovascular Diseases
(etiology, prevention & control)
- Clinical Trials, Phase III as Topic
- Down-Regulation
- Female
- Humans
- Hyperlipoproteinemia Type II
(blood, complications, drug therapy, genetics)
- Lipoprotein(a)
(blood)
- Male
- Middle Aged
- Oligodeoxyribonucleotides, Antisense
(therapeutic use)
- Oligonucleotides
(therapeutic use)
- Randomized Controlled Trials as Topic
- Risk Assessment
- Risk Factors
- Treatment Outcome
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