Safety and effects on the lipid and C-reactive protein plasma concentration of the association of ezetimibe plus atorvastatin in renal transplant patients treated by cyclosporine-A: a pilot study.
Ezetimibe (E) is a new cholesterol adsorption inhibitor which prevents the adsorption of dietary and biliary cholesterol by binding to a recently described cholesterol transporter. This pilot study was performed to evaluate the safety and the low-density lipoprotein (LDL)-C and C-reactive protein lowering efficacy of atorvastatin (A) and of the association of A plus E in five renal transplant patients with hypercholesterolemia and mild renal functional impairment receiving cyclosporine-A (CsA). Patients received for three periods, each of 3 weeks, A at a dose of 20 mg/day; A at a dose of 10 mg/day and finally, A 10 mg plus E 10 mg daily. The medications were well-tolerated and no important clinical or laboratory (muscle enzyme, creatinine clearance and CsA concentration) abnormalities were observed throughout the study period. A alone lead to target LDL-C values only in two of five patients and did not significantly reduce the mean CRP values. The combination of E plus A produced the lowest lipid levels and significantly reduced CRP mean values and allowed all patients to attain target levels of LDL-C: total cholesterol decreased from 240 +/- 42 (mean +/- S.D.) to 171 +/- 34 mg/dl, LDL-C from 129 +/- 32 to 87 +/- 21 mg/dl, plasma triglycerides from 330 +/- 54 to 194 +/- 71 mg/dl and CRP from 6.2 +/- 1.9 to 3.9 +/- 2.4 mg/l (P < 0.05 for all). This pilot study suggests that the co-administration of E and A at 10 mg/day in renal transplant patients receiving CsA is well-tolerated and effective in reducing important cardiovascular risk factors.
Panichi
V
V
Department of Internal Medicine, Nephrology Section, University of Pisa, Italy. vpanichi@med.unip.it
Manca-Rizza
G
G
Paoletti
S
S
Taccola
D
D
Consani
C
C
Sbragia
G
G
Mantuano
E
E
Marchetti
V
V
Carpi
A
A
Barsotti
G
G
D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069059:Atorvastatin; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism*; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000502:physiology*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D004338:Drug Combinations; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D008055:Lipids; D011758:Pyrroles; D014280:Triglycerides; D016572:Cyclosporine; D002097:C-Reactive Protein; D000069059:Atorvastatin; D000069438:Ezetimibe