Time course differences for statin-induced pleiotropic effects in hypercholesterolemic patients.
BACKGROUND
It is unclear whether there are temporal differences for the pleiotropic effects for different members of the statin class. The present study investigated differences in the short- and intermediate-term pleiotropic effects of statins in hypercholesterolemic patients.


METHODS
Thirty-five hypercholesterolemic patients were randomly treated with either atorvastatin or cerivastatin for 3 months. We measured fasting lipid concentrations, thiobarbituric acid reactive substances (TBARS), fibrinolytic parameters, and flow-mediated dilation of the brachial artery (FMD) at baseline and after 2 weeks and 3 months of therapy.


RESULTS
After 2 weeks of therapy, atorvastatin decreased the low density lipoprotein (LDL) cholesterol, small, dense LDL cholesterol (34+/-22 vs. 18+/-20%, P<0.01), remnant-like particles (RLP) cholesterol (8.8+/-6.0 vs. 5.1+/-2.6 mg/ml, P<0.01), and TBARS (3.3+/-1.0 vs. 3.1+/-0.9 nmol/ml, P<0.05), and cerivastatin decreased LDL cholesterol. After 3 months of therapy, atorvastatin decreased small dense LDL cholesterol (8+/-13%, P<0.0001) additionally, and cerivastatin decreased small, dense LDL cholesterol (51+/-11 vs. 12+/-22%, P<0.0001) and plasminogen activator inhibitor type 1 (68+/-32 vs. 51+/-21 ng/ml, P<0.05). FMD increased significantly in both groups after 2 weeks, although the relative change in FMD was greater with cerivastatin therapy after 2 weeks than atorvastatin therapy (60+/-78 vs. 23+/-26%, P<0.05). However, FMD was the same for both groups after 3 months (58+/-65 vs. 66+/-61%, NS), because atorvastatin additionally increased FMD. There was no correlation between these pleiotropic effects and the improvement in the lipid profile for either group.


CONCLUSIONS
These findings suggest that the degree of pleiotropic effect as well as the time course for the effect are different among members of the statin class of drugs.
Sakabe
Koichi
K
Department of Cardiology and Clinical Research, National Zentsuji Hospital, 2-1-1 Senyu-cho, Zentsuji, Kagawa 765-8507, Japan. ksakabe@jun.ncvc.go.jp
Fukuda
Nobuo
N
Wakayama
Katsunori
K
Nada
Teru
T
Shinohara
Hisanori
H
Tamura
Yoshiyuki
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011725:Pyridines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D013997:Time Factors
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008074:Lipoproteins; D011725:Pyridines; D011758:Pyrroles; D000069059:Atorvastatin; C086276:cerivastatin