title: Impact of induction immunosuppression on survival in heart transplant recipients: a contemporary analysis of agents.
abstract: BACKGROUND
  The impact of induction immunosuppression on long-term survival in heart transplant recipients is unclear. Over the past three decades, practices have varied as induction agents have changed and experiences grew. We sought to evaluate the effect of contemporary induction immunosuppression agents in heart transplant recipients with the primary endpoint of survival, utilizing national registry data.
  
  
  METHODS
  We queried the United Network for Organ Sharing (UNOS) data registry for all heart transplants from 1987 to 2012. We restricted our analysis to adult (≥18 yr) recipients performed from 2001-2011 (to allow for the potential for a minimum of 12 months post-transplant follow-up) who received either: no antibody based induction (NONE) or the contemporary agents (INDUCED) of either: basiliximab/daclizumab (IL-2Rab), alemtuzumab, or ATG/ALG/thymoglobulin. Kaplan-Meier estimates of the survival function as well as Cox proportional hazards models were utilized.
  
  
  RESULTS
  Of the 17 857 heart transplants that met the inclusion criteria, there were 4635 (26%) reported deaths during the follow-up period. There were 8216 (46%) patients who were INDUCED. Of the INDUCED agents, 55% were IL-2Rab, 4% alemtuzumab, and 40% ALG/ATG/thymoglobulin. Donor and recipient characteristics were evaluated. Overall, being INDUCED did not significantly affect survival in univariable (p = 0.522) and multivariable (p = 0.130) Cox models as well as a propensity score adjusted model (p = 0.733). Among those induced, ATG/ALG/thymoglobulin appeared to have superior survival as compared with IL-2Rab (log-rank p = 0.007, univariable hazard ratio [HR] = 0.886; 95% CI: 0.811-0.968; p = 0.522). However, in a multivariable Cox model that adjusted for recipient age, VAD, BMI, steroid use, CMV match, and ischemic time, the hazard ratio for ALG/ATG/thymoglobulin vs. IL-2Rab was no longer statistically significant (HR = 0.948; 95% CI: 0.850-1.058; p = 0.341).
  
  
  CONCLUSIONS
  In a contemporary analysis of heart transplant recipients, an overall analysis of induction agents does not appear to impact survival, as compared to no induction immunosuppression. While ALG/ATG/thymoglobulin appeared to have a beneficial effect on survival compared to IL-2Rab in the univariable model, this difference was no longer statistically significant once we adjusted for clinically relevant covariates.
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Whitson
authors.forename: Ahmet
authors.initials: A
authors.lastname: Kilic
authors.forename: Amy
authors.initials: A
authors.lastname: Lehman
authors.forename: Allison
authors.initials: A
authors.lastname: Wehr
authors.forename: Ayesha
authors.initials: A
authors.lastname: Hasan
authors.forename: Garrie
authors.initials: G
authors.lastname: Haas
authors.forename: Don
authors.initials: D
authors.lastname: Hayes
authors.forename: Chittoor B
authors.initials: CB
authors.lastname: Sai-Sudhakar
authors.forename: Robert S D
authors.initials: RS
authors.lastname: Higgins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000077552:Basiliximab; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000401:mortality*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000074323:Alemtuzumab; D000077552:Basiliximab; D000077561:Daclizumab; C512542:thymoglobulin
keywords: basiliximab; heart; immunosuppression; induction; survival; thymoglobulin; transplant