mTOR inhibitors and their secondary effects in cardiac transplant recipients: a descriptive study.
BACKGROUND
Mammalian target of rapamycin (mTOR) inhibitors are relatively new drugs in the field of cardiac transplantation (HT), hence the need for further study of their secondary effects. We described the nature and incidence of secondary effects of these drugs in a group of HT recipients.


METHODS
We studied 23 HT recipients aged 52 +/- 9 years (Male: 91%, body mass index: 27 +/- 3.7, ischemic cardiopathy: 52%, dilated cardiomyopathy: 39%) who were started on an mTOR inhibitor (everolimus: 65%, sirolimus: 35%) as part of their treatment. We have described the secondary effects detected during a follow-up period of 10.7 +/- 6 months.


RESULTS
The reasons for starting the drug were renal impairment (65%), tumors (26%), and others (8%). During follow-up, 17% of patients required a dose reduction and 12% required drug withdrawal: edemas: 4%, recurrent infection: 4%, and hemolytic-uremic syndrome: 4%. Drug-attributable edemas presented in 26% of patients. Thirty nine percent suffered an infection that required hospital admission, 89% of which were lung and all bacterial two patients died due to the infection). The mean time to first infection was 5 +/- 6 months. In patients who had a treatment change due to tumors, 50% experienced improvement. We did not detect alterations in cholesterol, triglycerides, creatinine, or leukocytes. There was a nonsignificant trend toward decreased hemoglobin and platelet levels (P = .07 and P = .056, respectively).


CONCLUSIONS
Lung infection was the principal complication among our patients treated with mTOR inhibitors. A large percentage required dose reduction (17%) and even drug withdrawal (12%) due to secondary effects.
Moro
J
J
Cardiac Failure and Transplant Unit, Cardiology Service, La Fe University Hospital, Valencia, Spain. moro@uv.es
Almenar
L
L
Martínez-Dolz
L
L
Izquierdo
M
M
Rueda
J
J
Arnau
M A
MA
Agüero
J
J
Sánchez-Lázaro
I
I
Ortiz
V
V
Salvador
A
A
D000328:Adult; D009202:Cardiomyopathies / Q000601:surgery; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000276:immunology; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011494:Protein Kinases / Q000502:physiology*; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D008055:Lipids; D000068338:Everolimus; D003404:Creatinine; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus