title: Conversion From Calcineurin Inhibitors to Mammalian Target-of-Rapamycin Inhibitors in Heart Transplant Recipients: A Meta-Analysis of Randomized Controlled Trials.
abstract: OBJECTIVE
  Conversion from calcineurin inhibitors (CNIs) to mammalian target-of-rapamycin inhibitors (mTORi) was systematically evaluated in heart transplant recipients (HTRs) for the first time.
  
  
  METHODS
  MEDLINE (PUBMED), EMBASE, Cochrane Library, and clinical trial registries were searched comprehensively. After screening for eligibility, the randomized controlled trials (RCTs) comparing continuation of CNI with conversion to mTORi therapy underwent review, quality assessment, and data extraction. Outcomes analyzed including creatinine clearance, serum creatinine level, rejection, adverse effects, and triglyceride levels were expressed as mean differences (MDs) or as risk ratios (RRs) with 95% confidence intervals (CIs).
  
  
  RESULTS
  This is the first systematic review evaluating converting from CNI to mTORi therapy in HTRs. A total of 4 RCTs (231 HTRs, 117 vs 114) were included in our analysis. Patients converted to mTORi had a higher creatinine clearance (MD, 19.31; 95% CI [11.16, 27.46]; P < .00001) and lower serum creatinine levels (MD, -0.15; 95% CI [-0.25, -0.05]; P = .002). Patients converted to mTORi had a significantly higher occurrence of adverse effects, which included skin diseases, gastrointestinal side effects, bone marrow suppression, and infections. There was no significant difference between the 2 groups regarding graft rejection and triglyceride levels (RR, 2.61; 95% CI [0.08, 81.25]; P = .58; MD, 22.89; 95% CI [-21.86, 67.63]; P = .32).
  
  
  CONCLUSIONS
  Conversion from CNI to mTORi therapy may improve the renal function in HTRs, but the patients may suffer from a high incidence of mTORi-associated adverse events. Therefore, conversion to mTORi must be carefully assessed for the benefits and risks.
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Rao
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Organ Transplantation Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: kidney5@163.com.
authors.forename: T
authors.initials: T
authors.lastname: Lin
mesh_terms: D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D057915:Drug Substitution; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D065095:Calcineurin Inhibitors; D047428:Protein Kinase Inhibitors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases