Conversion from cyclosporine microemulsion to tacrolimus-based immunoprophylaxis improves cholesterol profile in heart transplant recipients with treated but persistent dyslipidemia: the Canadian multicentre randomized trial of tacrolimus vs cyclosporine microemulsion.
BACKGROUND
Tacrolimus improves lipid profile in renal and liver transplant recipients. The impact of conversion from cyclosporine microemulsion (Neoral) to tacrolimus (Prograf) in a large randomized study of stable heart transplant recipients with treated but persistent mild dyslipidemia is reported.


METHODS
One hundred twenty-nine long-term (>or=12 months) cyclosporine microemulsion-treated heart transplant recipients with low-density lipoprotein cholesterol >2.5 mmol/liter and/or a total cholesterol/high-density lipoprotein cholesterol ratio >4 were recruited for the study. Complete lipid profile was assessed before (baseline) and after 6 months of treatment with either cyclosporine microemulsion maintenance (n=64) or tacrolimus conversion (n=65).


RESULTS
At 6 months, tacrolimus-converted patients exhibited a greater decrease in total cholesterol (from 5.51 +/- 0.16 to 4.88 +/- 1.22 mmol/liter [tacrolimus], vs 5.61 +/- 1.36 to 5.38 +/- 0.87 mmol/liter [cyclosporine]; p = 0.0078). This decrease in cholesterol was caused largely by a decrease in low-density lipoprotein cholesterol (-0.41 +/- 0.54 [tacrolimus] vs -0.13 +/- 0.55 [cyclosporine]; p=0.0018). There were no changes in high-density lipoprotein cholesterol and triglyceride levels, but apolipoprotein B therapy was reduced in tacrolimus-converted vs cyclosporine-maintained patients (p=0.0003). By 6 months, 23.7% of tacrolimus- vs 6.7% of cyclosporine-treated patients met the target lipid levels for high-risk patients (p=0.0094). Conversion from cyclosporine to tacrolimus resulted in decreases in blood urea nitrogen, creatinine, and uric acid without any changes in glucose, HbA(1C), and insulin levels.


CONCLUSIONS
Conversion from cyclosporine microemulsion- to tacrolimus-based immunoprophylaxis resulted in decreased cholesterol, apolipoprotein B, urea, creatinine, and uric acid without any clinically evident perturbation of glucose metabolism in stable heart transplant recipients with treated but persistent mild dyslipidemia.
White
Michel
M
Research Center of Montreal Heart Institute, Montreal, Quebec. michel.white@icm-mhi.org
Haddad
Haissam
H
Leblanc
Marie-Hélène
MH
Giannetti
Nadia
N
Pflugfelder
Peter
P
Davies
Ross
R
Isaac
Debra
D
Burton
Jeffrey
J
Chan
Michael
M
Azevedo
Eduardo
E
Howlett
Jonathan
J
Ignaszewski
Andrew
A
Busque
Stéphane
S
Cantarovich
Marcello
M
Ferguson
Ralph
R
Genest
Jacques
J
Ross
Heather
H
D000328:Adult; D000368:Aged; D001794:Blood Pressure; D002170:Canada; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D007166:Immunosuppressive Agents; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D016559:Tacrolimus