LOW-DOSE CYCLOSPORINE TREATMENT FAILS TO PREVENT CORONARY LUMINAL NARROWING AFTER HEART-TRANSPLANTATION

Background: Cyclosporine has been reported to induce endothelial dysfu nction, arterial vasculitis, and accelerated atherosclerosis in experi mental models. The purpose of the present study was to evaluate whethe r low-dose cyclosporine treatment started 1 year after heart transplan tation reduces graft coronary artery narrowing compared with conventio nal 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 mu g/L; group A; n = 15) or usual cyclosporine dosage (target levels 4 00 to 600 mu g/L; group B; n = 15). Proximal and distal diameters of t he left anterior descending, circumflex, and right coronary arteries w ere measured by quantitative coronary angiography at baseline (1 year after transplantation) and at 2 and 3 years after transplantation. Res ults: One major cardiac event occurred in group A (retransplantation) and two in group B (sudden deaths). Moderate to severe allograft rejec tion (International Society for Heart and Lung Transplantation score 3 A or higher) occurred in seven patients in group A and five in group B during the study period. Mean biopsy sample rejection score during th e 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 eviden ce of vascular disease was observed in four patients of group A and in one patient of group B. Proximal coronary artery diameter was slightl y, although not significantly, reduced in both groups at follow-up ang iography. Distal segments showed a significant diameter reduction, whi ch 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 reduct ion started 1 year after heart transplantation is ineffective in reduc ing coronary luminal narrowing and may be associated with an increased prevalence of cardiac allograft vasculopathy, especially in the dista l 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 earl ier time after heart transplantation.