Cardiac allograft vasculopathy prevention: Difference between revisions
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====Mycophenolate mofetil==== | ====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]] <ref name="pmid15896747">{{cite journal| author=Eisen HJ, Kobashigawa J, Keogh A, Bourge R, Renlund D, Mentzer R et al.| title=Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients. | journal=J Heart Lung Transplant | year= 2005 | volume= 24 | issue= 5 | pages= 517-25 | pmid=15896747 | doi=10.1016/j.healun.2005.02.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15896747 }} </ref>. | * Studies have shown trend towards a lower maximal intimal thickness on [[IVUS]], lower incidence of retransplantation and death with [[mycophenolate]] when compared to [[azathioprine]] <ref name="pmid15896747">{{cite journal| author=Eisen HJ, Kobashigawa J, Keogh A, Bourge R, Renlund D, Mentzer R et al.| title=Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients. | journal=J Heart Lung Transplant | year= 2005 | volume= 24 | issue= 5 | pages= 517-25 | pmid=15896747 | doi=10.1016/j.healun.2005.02.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15896747 }} </ref>. | ||
* Side effect profile: [[chest pain]], [[hypertension]]/[[hypotension]], [[tachycardia]], [[peripheral edema]], [[headache]], [[fever]], [[rash]], [[abdominal pain]], [[nausea]], [[diarrhea]]/[[constipation]], [[leukopenia]], [[anemia]], [[thrombocytopenia]], [[liver function test]] abnormalities, abnormal [[creatinine]] and [[BUN]], increased risk for infections | |||
====Calcineurin inhibitors==== | ====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. | * 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. | ||
Revision as of 14:32, 14 October 2014
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Cardiac allograft vasculopathy Microchapters |
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Differentiating Cardiac allograft vasculopathy from other Diseases |
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Diagnosis |
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Case Studies |
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Cardiac allograft vasculopathy prevention On the Web |
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American Roentgen Ray Society Images of Cardiac allograft vasculopathy prevention |
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Directions to Hospitals Treating Cardiac allograft vasculopathy |
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Risk calculators and risk factors for Cardiac allograft vasculopathy prevention |
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 currently not 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 [2]. Similar results were found in trials that studied sirolimus [3].
- Side effect profile:
- Everolimus: increase in serum creatinine levels, hyperlipidemia, anemia, thrombocytopenia, peripheral edema, hypertension. However, opportunistic viral infections less often seen.
- Sirolimus: Similar to everolimus, however recent reports of impaired wound healing have been reported in renal transplant patients.
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 [4].
- Side effect profile: chest pain, hypertension/hypotension, tachycardia, peripheral edema, headache, fever, rash, abdominal pain, nausea, diarrhea/constipation, leukopenia, anemia, thrombocytopenia, liver function test abnormalities, abnormal creatinine and BUN, increased risk for infections
Calcineurin inhibitors
- The use of 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
- ↑ 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.
- ↑ Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler HA; et al. (2003). "Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients". N Engl J Med. 349 (9): 847–58. doi:10.1056/NEJMoa022171. PMID 12944570.
- ↑ Matsuo Y, Cassar A, Yoshino S, Flammer AJ, Li J, Gulati R; et al. (2013). "Attenuation of cardiac allograft vasculopathy by sirolimus: Relationship to time interval after heart transplantation". J Heart Lung Transplant. 32 (8): 784–91. doi:10.1016/j.healun.2013.05.015. PMC 3727915. PMID 23856215.
- ↑ Eisen HJ, Kobashigawa J, Keogh A, Bourge R, Renlund D, Mentzer R; et al. (2005). "Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients". J Heart Lung Transplant. 24 (5): 517–25. doi:10.1016/j.healun.2005.02.002. PMID 15896747.