Cross-over trial of intensive monotherapy with atorvastatin and combined therapy with atorvastatin and colestimide for Japanese familial hypercholesterolemia.
BACKGROUND
In familial hypercholesterolemia (FH), low-density lipoprotein-cholesterol (LDL-C)-lowering therapy is important to avoid predisposition to coronary artery disease. This study investigated the advantages of combined therapy with atorvastatin and colestimide vs intensive monotherapy with atorvastatin.


RESULTS
The trial used a randomized cross-over design consisting of 2 16-week periods of open-label drug therapy. Among the 24 initial patients, 17 heterozygous FH patients (age: 54.1 years; 5 males) were enrolled after 20 mg/day atorvastatin failed to achieve their target level. The patients received 20 mg/day atorvastatin and 3 g/day colestimide or 40 mg/day atorvastatin. Fifteen patients completed the trial and their LDL-C reduced from 5.07 +/- 1.10 mmol/L to 3.76 +/- 0.90 mmol/L with the combined therapy and to 3.81 +/- 0.50 mmol/L with the intensive monotherapy. Although the 2 therapies showed comparable mean effects for decreasing LDL-C, similar adverse reaction and cost, each therapy was predominantly more effective in some patients than in others. The triglyceride and high-density lipoprotein cholesterol levels were similar in both therapies.


CONCLUSIONS
To achieve the therapeutic target of LDL-C level for refractory FH, the LDL-C-lowering therapy selected can be either intensive monotherapy or combined therapy as the next to standard statin therapy.
Tasaki
Hiromi
H
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan. h-tasaki@med.uoeh-u.ac.jp
Miyamoto
Masaharu
M
Kubara
Takahiro
T
Kamezaki
Fumihiko
F
Tanaka
Seiya
S
Yamashita
Kazuhito
K
Tsutsui
Masato
M
Nakashima
Yasuhide
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D004811:Epichlorohydrin / Q000627:therapeutic use*; D005260:Female; D006580:Genetic Carrier Screening; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D011758:Pyrroles / Q000627:therapeutic use*; D012117:Resins, Synthetic / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D007093:Imidazoles; D011758:Pyrroles; D012117:Resins, Synthetic; D014280:Triglycerides; C417427:colestimide; D004811:Epichlorohydrin; D000069059:Atorvastatin