Maintenance immunosuppression in heart transplantation: insights from network meta-analysis of various immunosuppression regimens.

Previous studies have reported superiority of mechanistic target-of-rapamycin (mTOR) antagonists (mTA) over calcineurin inhibitors (CNI) as part of maintenance immunosuppression (IS) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). MEDLINE and EMBASE were searched through October 2019 for studies comparing maintenance IS with mTA + antimetabolites (AM), CNI + mTA or CNI + AM post HT. The main outcomes were all-cause mortality, CAV, acute rejection, CMV infections, and change in eGFR. To compare different IS antagonists, a random-effects network meta-analysis was performed. We used p-scores to rank best treatments per outcome. Our search identified fifteen eligible studies (5 studies comparing mTA + AM vs. CNI + AM, 9 comparing CNI + mTA vs. CNI + AM, 1 comparing mTA + AM vs. CNI + mTA, 8 using everolimus and 7 sirolimus as mTA) reporting the selected outcomes. We did not identify any statistical difference in all-cause mortality among the three IS regimens without heterogeneity among studies. CAV rates were significantly lower with CNI + mTA (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.3-0.92). Acute rejection rates were significantly lower with CNI + AM (OR 0.26, 95% CI 0.12-0.56) and with CNI + mTA (OR 0.16, 95% CI 0.07-0.33) compared with mTA + AM without significant heterogeneity (I2 = 43%, p = 0.9). CMV infections were significantly lower with mTA + AM (OR 0.13, 95% CI 0.03-0.46) and with CNI + mTA (OR 0.27, 95% CI 0.2-0.38) compared with CNI + AM without heterogeneity. mTA + AM led to higher eGFR compared with CNI + AM (9.06 ml/min/1.73 m2, 95% CI 3.15-14.97) and CNI + Mta (9.64 ml/min/1.73 m2, 95% CI 0.91-18.36), but the heterogeneity among studies was significant. CNI + mTA ranked better for CAV (p = 0.78), and acute rejection (p = 0.99) while mTA + AM for CMV infection (p = 0.94) and improvement in renal function (p = 0.93) than other regimens. Different IS regimens have similar effects on survival post HT, but CNI + mTA was associated with lower CAV rates, and acute rejection, while mTA + AM with less CMV infection post HT.