title: Tolerance profile of the proliferation signal inhibitors everolimus and sirolimus in heart transplantation.
abstract: BACKGROUND
  The side effects of proliferation signal inhibitors (PSIs) have been characterized as a class. However, it would be convenient to assess them according to the molecule.
  
  
  OBJECTIVE
  To assess prospectively the tolerance of PSIs among heart transplant (HT) patients.
  
  
  METHODS
  We studied 56 HT patients who sequentially received PSIs to either withdraw (77%) or reduce the dosage of a calcineurin inhibitor; 42 received everolimus (EVE) and 14 sirolimus (SRL). We analyzed the demographic variables, side effects, and need to withdraw the drug during a median follow-up period of 365 days.
  
  
  RESULTS
  No differences between groups were observed upon analysis of the clinical and demographic variables when the treatment was changed owing to renal dysfunction (67%) or tumor (32%). No difference between groups was observed over the follow-up period (P = .28). Infection was the most common side effect, 28.6%: EVE, 14.3% versus SRL, 71.4% (P < .0001). Edema occurred in 26.8% of patients: EVE, 14.3% versus SRL, 64.3% (P = .001); diarrhea in 5.4% of patients: EVE, 2.4% versus SRL, 14.3% (P = .15). Treatment was withdrawn in 23.2% of the patients due to intolerance: EVE, 11.9% versus SRL, 57.1% (P < .0001). EVE showed significantly better survival without edema or infections or used for drug withdrawal upon Kaplan-Meier analysis, (P = .01; P = .0005; P = .0097). Only SRL use was shown to be an independent predictor of side effects.
  
  
  CONCLUSIONS
  Edema and infections are the main problems caused by PSIs. EVE may display a better tolerance profile than SRL.
authors.affiliation: Research Foundation, HU La Fe, Valencia; Heart Failure and Transplantation Department, Cardiology, HU La Fe, Valencia, Spain. moro@uv.es
authors.forename: J A
authors.initials: JA
authors.lastname: Moro
authors.forename: L
authors.initials: L
authors.lastname: Almenar
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Dolz
authors.forename: I
authors.initials: I
authors.lastname: Sánchez-Lázaro
authors.forename: J
authors.initials: J
authors.lastname: Agüero
authors.forename: A
authors.initials: A
authors.lastname: Salvador
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D003327:Coronary Disease / Q000601:surgery; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004487:Edema / Q000139:chemically induced; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007239:Infections / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus