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.
Research Center of Montreal Heart Institute, Montreal, Quebec. michel.white@icm-mhi.org
Michel
M
White
Haissam
H
Haddad
Marie-Hélène
MH
Leblanc
Nadia
N
Giannetti
Peter
P
Pflugfelder
Ross
R
Davies
Debra
D
Isaac
Jeffrey
J
Burton
Michael
M
Chan
Eduardo
E
Azevedo
Jonathan
J
Howlett
Andrew
A
Ignaszewski
Stéphane
S
Busque
Marcello
M
Cantarovich
Ralph
R
Ferguson
Jacques
J
Genest
Heather
H
Ross
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