Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease.
OBJECTIVE
To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin.


METHODS
Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks.


RESULTS
Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks.


CONCLUSIONS
Although the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.
Division of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama City, Kanagawa 232-0024, Japan. kozookada@gmail.com
Kozo
K
Okada
Noriaki
N
Iwahashi
Tsutomu
T
Endo
Hideo
H
Himeno
Kazuki
K
Fukui
Shunichi
S
Kobayashi
Makoto
M
Shimizu
Yuji
Y
Iwasawa
Yukiko
Y
Morita
Atsushi
A
Wada
Tomohiko
T
Shigemasa
Yasuyuki
Y
Mochida
Tomoaki
T
Shimizu
Reimin
R
Sawada
Kazuaki
K
Uchino
Satoshi
S
Umemura
Kazuo
K
Kimura
D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007564:Japan; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000068718:Rosuvastatin Calcium; D012697:Serine Endopeptidases / Q000097:blood; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010840:Phytosterols; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C021273:campesterol; C001521:lathosterol; D000068718:Rosuvastatin Calcium; D002784:Cholesterol; D000069059:Atorvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe