A combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy.
Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been reported to decrease the cholesterol saturation index (CSI) in duodenal bile in humans and to prevent formation of cholesterol gallstones in animal studies. We performed a prospective study to evaluate the role of HMG-CoA reductase inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent gallstones in a gallbladder opacifying at drip infusion cholecystography were treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12 months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid levels were assessed and ultrasonographic examination of the gallbladder was performed at baseline and at 3-month intervals during treatment. Duodenal bile sampling was performed in five patients in each group at baseline and after 12 months of treatment. Plasma cholesterol decreased significantly in group 1 but not in group 2. In solitary gallstone cases, no significant difference in dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12, 33%). In contrast, the dissolution rate in multiple gallstone cases was significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01) but did not significantly differ between the two groups. These results suggest that combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than ursodeoxycholic acid monotherapy in patients with multiple gallstones.
Tazuma
S
S
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Kajiyama
G
G
Mizuno
T
T
Yamashita
G
G
Miura
H
H
Kajihara
T
T
Hattori
Y
Y
Miyake
H
H
Nishioka
T
T
Hyogo
H
H
Sunami
Y
Y
Yasumiba
S
S
Ochi
H
H
Matsumoto
T
T
Abe
A
A
Adachi
K
K
Omata
F
F
Ueno
F
F
Sugata
F
F
Ohguri
S
S
Shibata
H
H
Kokubu
S
S
D001646:Bile / Q000737:chemistry; D002769:Cholelithiasis / Q000737:chemistry / Q000188:drug therapy*; D002784:Cholesterol / Q000032:analysis* / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D019821:Simvastatin