A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: Decreased hyperlipidemia and hypertension with tacrolimus

Background: Tacrolimus-based immunosuppression seems safe and effective in liver and kidney transplantation. To assess the safety and efficacy of tacr olimus (TAC)-based immunosuppression after cardiac transplantation as well as the relative impact of tacrolimus on immunosuppression-related side effe cts such as hypertension and hyperlipidemia, we conducted a prospective, ra ndomized, open-label, multicenter study of otherwise identical tacrolimus- and cyclosporine-based immunosuppressive regimens in adult patients undergo ing cardiac transplantation. Methods:Eighty-five adult patients (pts) at six United States cardiac trans plant centers, undergoing their first cardiac transplant procedure, were pr ospectively randomized to receive either TAG-based (n = 39) or cyclosporine (CYA)-based (n = 46) immunosuppression. All pts received a triple-drug pro tocol with 15 pts (18%) receiving peri-operative OKT3 to delay TAC/CYA due to pre-transplant renal dysfunction. Endomyocardial biopsies were performed at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 24, and 52. The study duration was 12 m onths. Results: Patients were mostly male (87%) Caucasian (90%) with a mean age of 54 years and primary diagnoses of coronary artery disease (55%) and idiopa thic dilated cardiomyopathy (41%). There were no significant demographic di fferences between groups. Patient and allograft survival were not different in the two groups. The probability and overall incidence of each grade of rejection, whether treated or not, and the types of treatment required did not differ between the groups. At baseline and through 12 months of follow- up, chemistry and hematology values were similar between the groups except serum cholesterol was higher in the CYA group at 3, 6, and 12 months (239 v s 205 mg/dL, 246 vs 191 mg/dL, 212 vs 186 mg/dL, respectively, p < 0.001). Likewise, LDL-cholesterol, HDL-cholesterol and triglycerides were significa ntly higher in the CYA group. More CYA patients received therapy for hyperc holesterolemia (71% vs 41% at 12 months, p = 0.01). There were no significa nt differences in renal function, hyperglycemia, hypomagnesemia, or hyperka lemia during the first 12 months. More; CYA patients developed new-onset hy pertension requiring pharmacologic treatment (71% vs 48%, p = 0.05). The in cidence of infection was the same for the two groups (2.6 episodes/pt/12 mo nth follow-up). Conclusion: Tacrolimus-based immunosuppression seems effective for rejectio n prophylaxis during the first year after cardiac transplantation and is as sociated with less hypertension and hyperlipidemia and no difference in ren al function, hyperglycemia or infection incidence when compared to cyclospo rine-based immunosuppression.