Multidisciplinary insights on clinical guidance for the use of proliferation signal inhibitors in heart transplantation.
Proliferation signal or mammalian target-of-rapamycin inhibitors (PSI/mTOR inhibitors), everolimus and sirolimus, provide attractive options for use in heart transplantation because they are immunosuppressive and anti-proliferative. PSI/mTOR inhibitors work synergistically with calcineurin inhibitors (CNIs) and thus permit the minimization of CNIs without compromising efficacy. This approach is advantageous for the majority of heart transplant recipients and might provide particular benefit in specific cases, such as patients with cardiac allograft vasculopathy, malignancies and renal dysfunction, or in patients intolerant to other immunosuppressive agents. Drawing on the expertise of transplant cardiologists, cardiac surgeons and nephrologists, we addressed the assessment of renal function; management of adverse events associated with this class of drugs; and clinical guidance, specifically for the use of everolimus, including patient selection, indications for treatment and practicalities of drug initiation and monitoring.
Zuckermann
Andreas
A
Department of Cardio-Thoracic Surgery, Medical University of Vienna, Vienna, Austria.
Manito
Nicolas
N
Epailly
Eric
E
Fiane
Arnt
A
Bara
Christoph
C
Delgado
Juan F
JF
Lehmkuhl
Hans
H
Ross
Heather
H
Eisen
Howard
H
Chapman
Jeremy
J
Valantine
Hannah
H
D000068338:Everolimus; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D033183:Interdisciplinary Communication; D007677:Kidney Function Tests; D008297:Male; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D011379:Prognosis; D011507:Proteinuria / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013530:Surgical Wound Infection / Q000139:chemically induced / Q000453:epidemiology; D014181:Transplantation Immunology / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus