Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: A randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine: Results at 24 months after transplantation

Background The widespread use of cyclosporine has improved the survival of cardiac transplant patients as a result of reduced morbidity and mortality from rejection and infection. The original oil-based form of cyclosporine d emonstrated unpredictable absorption resulting in an increased frequency of acute and chronic rejection in patients with poor bioavailability. The pri mary endpoints of the present, prospective, randomized multicenter, double- blind trial were to compare the efficacy of the micro-emulsion form of cyco lsporine (CsA-NL) with the oil-based formulation as determined by cardiac a llograft and recipient survival and the incidence and severity of the acute rejection episodes and to determine the safety and tolerability of CsA-NL compared with Sandimmune CsA-(SRa) in the study population. The 6-month ana lysis of the study showed reduced number of CsA-NL patients requiring antil ymphocyte antibody therapy for rejection, fewer international Society of He art and Lung Transplantation grade greater than or equal to 3A rejections i n female patients and fewer infections. Our report represents the final ana lysis of the results 24 months after transplantation. Methods. A total of 380 patients undergoing de novo cardiac transplants at 24 centers in the United States. Canada, and Europe were enrolled in this d ouble-blind, randomized trial evaluating the efficacy and safety of CsA-NL versus CsA-SM, Acute allograft rejection was diagnosed by endomyocardial bi opsy and graded according to the International Society of Heart and Lung Tr ansplantation nomenclature. Kaplan-Meier analysis and Fisher's exact test w ere used for comparisons between groups. Results. After 24 months, allograft and recipient survival were identical i n both groups. There were fewer CsA-NL patients (6.9%) requiring antilympho cyte antibody therapy for rejection than in the CsA-SM-treated patient grou p (17.7%, P = 0.002), There were fewer discontinuations of study drug for t reatment failures in the CsA-NL groups (7; 3.7%) compared with the CsA-SM g roup (18; 9.4%, P = 0.037). The average corticosteroid dose was lower in th e CsA-NL group (0.37 mg/kg/day) compared with the CsA-SM group (0.48 mg/kg/ day, P = 0.034) over the 24-month study period. Overall, there was no diffe rence in blood pressure or creatinine between the two study groups. Conclusions. The final results of this multi-center, randomized study of tw o forms of cyclosporine confirmed that there were fewer episodes of rejecti on requiring antilymphocyte antibodies and fewer study discontinuations for treatment failures in CsA-NL-treated patients compared to those treated wi th CsA-SM, The use of CsA-NL did not predispose these patients to a higher risk of adverse events.