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After Cardiac Transplantation: Sirolimus acts as immunosuppressant Attenuates Allograft Vasculopathy

Writer and Curator: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN 

 

Sirolimus as primary immunosuppression attenuates allograft vasculopathy with improved late survival and decreased cardiac events after cardiac transplantation

Topilsky Y, Hasin T, Raichlin E, Boilson BA, Schirger JA, et al.
Circulation. 2012 Feb 7;125(5):708-20.    http://dx.doi.org/10.1161/CIRCULATIONAHA.111.040360. Epub 2011 Dec 29

BACKGROUND: We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant

  1. in the long-term attenuation of cardiac allograft vasculopathy progression and
  2. the effects on cardiac-related morbidity and mortality.
METHODS:  Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors.
  • Age,
  • sex,
  • ejection fraction, and
  • time from transplantation to baseline intravascular ultrasound study were not different (P>0.2 for all) between the groups;
  • neither were secondary immunosuppressants and
  • use of steroids.

Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later.

RESULTS:  Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%; P=0.0003) owing to
  1. reduced plaque volume in patients converted to sirolimus early (<2 years) after transplantation (P=0.05) and
  2. improved positive vascular remodeling (P=0.01) in patients analyzed late (>2 years) after transplantation.
Outcome analysis in 160 consecutive patients maintained on 1 therapy was performed regardless of performance of intravascular ultrasound examinations.
  1. Five-year survival was improved with sirolimus (97.4±1.8% versus 81.8±4.9%; P=0.006),
  2. There was freedom from cardiac-related events (93.6±3.2% versus 76.9±5.5%; P=0.002).
CONCLUSIONS:  Substituting calcineurin inhibitor with sirolimus as primary immunosuppressant
  1. attenuates long-term cardiac allograft vasculopathy progression and
  2. may improve long-term allograft survival owing to favorable coronary remodeling.
Because of the lack of randomization and retrospective nature of our analysis, the differences in outcome should be interpreted cautiously, and prospective clinical trials are required.

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Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization
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New Drug-Eluting Stent Works Well in STEMI
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Coronary Artery DiseaseMedical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents
Aviva Lev-Ari, PhD, RN
Table 1 Illustration

Table 1 Illustration (Photo credit: Libertas Academica)

Photograph of the Taxus drug-eluting stent, fr...

Photograph of the Taxus drug-eluting stent, from the web site of the U.S. Food and Drug Administration. (Photo credit: Wikipedia)

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