Cardiac allograft vasculopathy prevention: Difference between revisions

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* [[Sirolimus]] ([[Rapamycin]])
* [[Sirolimus]] ([[Rapamycin]])
* [[Everolimus]], a [[Immunosuppressive drugs#Drugs Acting on Immunophilins|Rapamycin derivative]]
* [[Everolimus]], a [[Immunosuppressive drugs#Drugs Acting on Immunophilins|Rapamycin derivative]]
* [[Immunosuppressive drugs#Drugs Acting on Immunophilins|Calcineurin inhibitors]], such as
** [[Cyclosporine]]
** [[Tacrolimus]]
* [[Corticosteroids]]
* [[Corticosteroids]]
* [[Mycophenolate mofetil]]
* [[Mycophenolate mofetil]]


===Everolimus and Sirolimus===
====Everolimus and Sirolimus====
* Act by inhibiting mTOR (mammalian target), thereby having anti-proliferative effects in response to allo-antigens.
* Act by inhibiting mTOR (mammalian target), thereby having anti-proliferative effects in response to allo-antigens.
* Everolimus is not currently FDA approved for clinical use in the United States.  
* Everolimus is not currently FDA approved for clinical use in the United States.  
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** Sirolimus: Similar to everolimus, however recent reports of impaired wound healing have been reported in renal transplant patients.
** Sirolimus: Similar to everolimus, however recent reports of impaired wound healing have been reported in renal transplant patients.


===Calcineurin inhibitors===
====Mycophenolate mofetil====
The use of [[Immunosuppressive drugs#Drugs Acting on Immunophilins|calcineurin inhibitors]] i.e [[cyclosporin]] and [[tacrolimus]] have not been shown to lower the risk of developing CAV. This suggests that other immunological pathways may exists that play a role in the pathogenesis of CAV. Moreover, side effects from use of these drugs leads to a high incidence of not only [[chronic renal disease]] but also [[hypertension]] and [[hyperlipidemia]] which in turn may accelerate the process of CAV.
* Studies have shown trend towards a lower maximal intimal thickness on [[IVUS]], lower incidence of retransplantation and death with [[mycophenolate]] when compared to [[azathioprine]].
 
====Calcineurin inhibitors====
* The use of [[Immunosuppressive drugs#Drugs Acting on Immunophilins|calcineurin inhibitors]] i.e [[cyclosporin]] and [[tacrolimus]] have not been shown to lower the risk of developing CAV.  
* This suggests that other immunological pathways may exists that play a role in the pathogenesis of CAV. Moreover, side effects from use of these drugs leads to a high incidence of not only [[chronic renal disease]] but also [[hypertension]] and [[hyperlipidemia]] which in turn may accelerate the process of CAV.


==References==
==References==

Revision as of 22:46, 11 October 2014

Cardiac allograft vasculopathy Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2] Raviteja Guddeti, M.B.B.S. [3]

Overview

Prevention

As the pathogenesis of CAV consists of both immunological and non-immunological insults, it has been suggested that preventative strategies should consist of control of risk factors for CAV and optimal immunosuppressive therapy. However, the best preventative strategy to delay development of CAV is yet to be determined.

Optimization of Immunosuppressive Therapy

Options for immunosuppressive therapy for prevention of CAV include [1]:

Everolimus and Sirolimus

  • Act by inhibiting mTOR (mammalian target), thereby having anti-proliferative effects in response to allo-antigens.
  • Everolimus is not currently FDA approved for clinical use in the United States.
  • Associated with significantly reduced incidence of graft rejection.
  • Serial IVUS studies to evaluate intimal proliferation demonstrated smaller increase in maximal intimal thickness and intimal index in patients taking everolimus. Similar results were found in trials that studied sirolimus.
  • Side effect profile:

Mycophenolate mofetil

  • Studies have shown trend towards a lower maximal intimal thickness on IVUS, lower incidence of retransplantation and death with mycophenolate when compared to azathioprine.

Calcineurin inhibitors

References

  1. Mehra MR (2006). "Contemporary concepts in prevention and treatment of cardiac allograft vasculopathy". Am J Transplant. 6 (6): 1248–56. doi:10.1111/j.1600-6143.2006.01314.x. PMID 16686747.

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