Everolimus: efficacy and safety in cardiac transplantation.
BACKGROUND
Prognosis after cardiac transplantation continues to improve with long-term outcomes limited by malignancy and coronary allograft vasculopathy (CAV). Everolimus may potentially reduce these late term complications, while maintaining the low cellular rejection rates seen with standard therapy.


METHODS
Multiple studies have demonstrated the efficacy of everolimus in reducing acute rejection in heart transplant patients, progression and development of CAV, and the prevention and treatment of common malignancies, including skin cancer and Kaposi sarcoma. This review re-examines these studies with a focus on patient tolerability and safety.


RESULTS
Tolerability and safety of everolimus remain a concern with pneumonitis, effusions, mouth ulcers, edema and impaired wound healing associated with morbidity and mortality. Studies have repeatedly demonstrated renal function deterioration with concomitant everolimus and a standard dose calcineurin inhibitor (CNI). This impact can be partly reduced with CNI dose reduction without an increase in the rate of rejection.


CONCLUSIONS
If future studies confirm reduced CAV and malignancy rates, everolimus will become an important agent in de novo and maintenance immunotherapy in cardiac transplantation. Patient centered immunotherapy is preferred to protocol-based immunotherapy as it allows tailoring of immune therapy to each individual patient's rejection risk and side profile.
Schaffer
S Allan
SA
University Health Network, University of Toronto, Toronto General Hospital, Divisions of Cardiology and Transplantation, 585 University Ave, Toronto, Ontario M5G 2N2, Canada.
Ross
Heather J
HJ
D000818:Animals; D004198:Disease Susceptibility; D050171:Dyslipidemias / Q000139:chemically induced; D000068338:Everolimus; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008171:Lung Diseases / Q000139:chemically induced; D051379:Mice; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009369:Neoplasms / Q000209:etiology* / Q000276:immunology; D011183:Postoperative Complications / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014652:Vascular Diseases / Q000139:chemically induced*; D014945:Wound Healing / Q000187:drug effects
D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus