Low-dose cyclosporine treatment fails to prevent coronary luminal narrowing after heart transplantation.
BACKGROUND
Cyclosporine has been reported to induce endothelial dysfunction, arterial vasculitis, and accelerated atherosclerosis in experimental models. The purpose of the present study was to evaluate whether low-dose cyclosporine treatment started 1 year after heart transplantation reduces graft coronary artery narrowing compared with conventional cyclosporine doses.


METHODS
One year after heart transplantation, 30 patients were randomly assigned to receive low-dose cyclosporine A (whole-blood polyclonal cyclosporine target trough levels 200 to 400 micrograms/L; group A; n = 15) or usual cyclosporine dosage (target levels 400 to 600 micrograms/L; group B; n = 15). Proximal and distal diameters of the left anterior descending, circumflex, and right coronary arteries were measured by quantitative coronary angiography at baseline (1 year after transplantation) and at 2 and 3 years after transplantation.


RESULTS
One major cardiac event occurred in group A (retransplantation) and two in group B (sudden deaths). Moderate to severe allograft rejection (International Society for Heart and Lung Transplantation score 3A or higher) occurred in seven patients in group A and five in group B during the study period. Mean biopsy sample rejection score during the same period was increased in group A compared with that in group B (1.44 +/- 0.63 versus 1.05 +/- 0.59; p < 0.05). New angiographic evidence of vascular disease was observed in four patients of group A and in one patient of group B. Proximal coronary artery diameter was slightly, although not significantly, reduced in both groups at follow-up angiography. Distal segments showed a significant diameter reduction, which was greater in group A than in group B (-9.7% +/- 1.1% and -5.2% +/- 1.3%, respectively; p < 0.05).


CONCLUSIONS
Cyclosporine dose reduction started 1 year after heart transplantation is ineffective in reducing coronary luminal narrowing and may be associated with an increased prevalence of cardiac allograft vasculopathy, especially in the distal coronary tree. Low-dose cyclosporine treatment may slightly enhance the risk of allograft rejection. Further investigations are needed to evaluate the effects of cyclosporine dose reduction started at an earlier time after heart transplantation.
Vassalli
G
G
Department of Medicine, Cardiology, University Hospital, Zurich, Switzerland.
Kaski
J C
JC
Tousoulis
D
D
Kiowski
W
W
Turina
M
M
Follath
F
F
Gallino
A
A
D000328:Adult; D001706:Biopsy; D017023:Coronary Angiography; D003327:Coronary Disease / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*; D006084:Graft Rejection / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine