Five-year results of a randomized, single-center study of tacrolimus vs microemulsion cyclosporine in heart transplant patients.
BACKGROUND
Previous multicenter, randomized trials, lacking standardized post-transplant protocols, have compared tacrolimus (Tac) and cyclosporine (CyA, Sandimmune) and demonstrated similar outcomes with some different adverse effects. The microemulsion form of CyA (mCyA, Neoral) has replaced Sandimmune CyA as the more widely utilized CyA formulation. This is the first 5-year follow-up study of a large, single-center trial (n = 67) under a standardized post-transplant protocol comparing Tac and mCyA.


METHODS
Sixty-seven heart transplant patients were randomized to Tac (n = 33) or mCyA (n = 34), both in combination with corticosteroids and azathioprine without cytolytic induction. Five-year end-points included survival, Grade > or = 3A or treated rejection, angiographic cardiac allograft vasculopathy (CAV; any lesion > or = 30% stenosis), renal dysfunction (creatinine > or = 2.0 mg/dl), use of two or more anti-hypertensive medications, percent diabetic and lipid levels.


RESULTS
Five-year survival, freedom from Grade > or = 3A or any treated rejection and angiographic CAV, mean cholesterol level and percent diabetic were similar between the two groups. The Tac group had a significantly lower 5-year mean triglyceride level (Tac 97 +/- 34 vs mCyA 175 +/- 103 mg/dl, p = 0.011) and average serum creatinine level (Tac 1.2 +/- 0.5 mg/dl vs mCyA 1.5 +/- 0.4 mg/dl, p = 0.044). There was a trend toward fewer patients requiring two or more anti-hypertensive drugs in the Tac group (Tac 33% vs mCyA 59%, p = 0.065).


CONCLUSIONS
Tac and mCyA appear to be comparable with regard to 5-year survival, freedom from rejection and CAV. However, compared with mCyA, Tac appears to reduce the adverse effect profile for hypertriglyceridemia and renal dysfunction and the need for hypertensive medications.
Division of Cardiology, Department of Medicine, University of California, Los Angeles, California, USA. jonk@mednet.ucla.edu
Jon A
JA
Kobashigawa
J
J
Patel
H
H
Furukawa
J D
JD
Moriguchi
L
L
Yeatman
S
S
Takemoto
A
A
Marquez
J
J
Shaw
B T
BT
Oeser
S
S
Subherwal
G W
GW
Wu
J
J
Kawano
H
H
Laks
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D023921:Coronary Stenosis / Q000209:etiology / Q000517:prevention & control; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006331:Heart Diseases / Q000150:complications / Q000628:therapy; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D015228:Hypertriglyceridemia / Q000209:etiology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus