Can cyclosporine blood level be reduced to half after heart transplantation?
BACKGROUND
Cyclosporine (CsA) is widely used after heart transplantation. The purpose of this prospective randomized study was to evaluate the safety and efficacy of reduction of CsA blood level to one-half of the traditional blood concentration under a regimen of everolimus (EVL), CsA, and steroid.


METHODS
This prospective, 6 month, randomized, open-label study included adult (aged 18 to 65 years) recipients of a primary heart transplant with serum creatinine<or=2.8 mg/dL. Among 52 patients who underwent heart transplantation from December 2004 to March 2006 we excluded those who were hepatitis B or C carriers, who were recipients of organs from donors>60 years old, had cold ischemia time>6 hours, or had plasma renin activity>or=25%. All patients received CsA (C2 blood level 1000-1400 ng/mL), EVL (C0 target 3-8 ng/mL), and corticosteroids to day 60, before random entry into one of 2 groups: SE (C2 blood level from days 60-149=800-1200 ng/mL, and days 150-180 C2=600-1000 ng/mL), or RE group with CsA reduced by one-half after 3 months (days 90-149 C2=400-600 ng/mL, and from days 150-180 C2=300-500 ng/mL).


RESULTS
The 25 recipients eligible for this study included 13 patients in the SE and 12 in the RE group. There was no operative mortality in either group. No death or graft loss was noted within 6-months in either group. Mean serum creatinine at month 6 tended to be lower in the RE cohort (1.23+/-0.44 mg/dL versus 1.55+/-0.85 mg/dL; P=.093). Biopsy-proven acute rejection>or=grade 3A was observed in only 1 patient (7.7%), who was in the SE group. There were no acute rejection episodes associated with hemodynamic compromise. The incidences of adverse events in each group were similar.


CONCLUSIONS
Concentration-controlled EVL (C0 target 3-8 ng/mL) in combination with reduced CsA exposure of one-half the usual concentration achieved good efficacy and safety over 6 months. The renal function at 6 months among the RE group showed a trend toward improvement, suggesting a benefit of halving the target CsA blood level after heart transplantation.
Wang
S-S
SS
Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei, Taiwan. wangp@ntu.edu.tw
Chou
N-K
NK
Chi
N-H
NH
Huang
S-C
SC
Wu
I-H
IH
Wang
C-H
CH
Yu
H-Y
HY
Chen
Y-S
YS
Tsao
C-I
CI
Ko
W-J
WJ
Shun
C-T
CT
D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood*; D016572:Cyclosporine / Q000097:blood* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000068338:Everolimus; D005260:Female; D006331:Heart Diseases / Q000145:classification / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D014019:Tissue Donors / Q000706:statistics & numerical data; D055815:Young Adult
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D020123:Sirolimus