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Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial.

Arora, Satish ; Ueland, Thor ; Wennerblom, Bertil ; Sigurdadottir, Vilborg ; Eiskjär, Hans ; Bötker, Hans E ; Ekmehag, Björn LU ; Jansson, Kjell ; Mortensen, Svend-Aage and Saunamaki, Kari , et al. (2011) In Transplantation 92. p.235-243
Abstract
BACKGROUND.: Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown. METHODS.: In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8±4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression. RESULTS.: No significant difference in CAV progression was evident between the treatment groups (P=0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n=39), CAV progression was... (More)
BACKGROUND.: Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown. METHODS.: In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8±4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression. RESULTS.: No significant difference in CAV progression was evident between the treatment groups (P=0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n=39), CAV progression was attenuated with everolimus versus standard CNI (Δmaximal intimal thickness 0.00±0.04 and 0.04±0.04 mm, Δpercent atheroma volume 0.2%±3.0% and 2.6%±2.5%, and Δtotal atheroma volume 0.25±14.1 and 19.8±20.4 mm, respectively [P<0.05]). When considering patients receiving mycophenolate mofetil (MMF), accelerated CAV progression occurred with everolimus versus standard CNI (Δmaximal intimal thickness 0.06±0.12 vs. 0.02±0.06 mm and Δpercent atheroma volume 4.0%±6.3% vs. 1.4%±3.1%, respectively; P<0.05). The levels of C-reactive protein and vascular cell adhesion molecule-1 declined significantly with AZA+everolimus, whereas MMF+everolimus patients demonstrated a significant increase in levels of C-reactive protein, vascular cell adhesion molecule-1, and von Willebrand factor. CONCLUSIONS.: Conversion to everolimus and reduced CNI does not influence CAV progression among maintenance HTx recipients. However, background immunosuppressive therapy is important as AZA+everolimus patients demonstrated attenuated CAV progression and a decline in inflammatory markers, whereas the opposite pattern was seen with everolimus+MMF. The different effect of everolimus when combined with AZA versus MMF could potentially reflect hitherto unknown interactions. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Transplantation
volume
92
pages
235 - 243
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000292633000023
  • pmid:21677600
  • scopus:79960305705
  • pmid:21677600
ISSN
1534-6080
DOI
10.1097/TP.0b013e31822057f1
language
English
LU publication?
yes
id
7973d7f2-eaaa-45d3-8b6a-9d7044697bbf (old id 2007983)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21677600?dopt=Abstract
date added to LUP
2016-04-04 09:14:04
date last changed
2022-03-07 23:43:19
@article{7973d7f2-eaaa-45d3-8b6a-9d7044697bbf,
  abstract     = {{BACKGROUND.: Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown. METHODS.: In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8±4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression. RESULTS.: No significant difference in CAV progression was evident between the treatment groups (P=0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n=39), CAV progression was attenuated with everolimus versus standard CNI (Δmaximal intimal thickness 0.00±0.04 and 0.04±0.04 mm, Δpercent atheroma volume 0.2%±3.0% and 2.6%±2.5%, and Δtotal atheroma volume 0.25±14.1 and 19.8±20.4 mm, respectively [P&lt;0.05]). When considering patients receiving mycophenolate mofetil (MMF), accelerated CAV progression occurred with everolimus versus standard CNI (Δmaximal intimal thickness 0.06±0.12 vs. 0.02±0.06 mm and Δpercent atheroma volume 4.0%±6.3% vs. 1.4%±3.1%, respectively; P&lt;0.05). The levels of C-reactive protein and vascular cell adhesion molecule-1 declined significantly with AZA+everolimus, whereas MMF+everolimus patients demonstrated a significant increase in levels of C-reactive protein, vascular cell adhesion molecule-1, and von Willebrand factor. CONCLUSIONS.: Conversion to everolimus and reduced CNI does not influence CAV progression among maintenance HTx recipients. However, background immunosuppressive therapy is important as AZA+everolimus patients demonstrated attenuated CAV progression and a decline in inflammatory markers, whereas the opposite pattern was seen with everolimus+MMF. The different effect of everolimus when combined with AZA versus MMF could potentially reflect hitherto unknown interactions.}},
  author       = {{Arora, Satish and Ueland, Thor and Wennerblom, Bertil and Sigurdadottir, Vilborg and Eiskjär, Hans and Bötker, Hans E and Ekmehag, Björn and Jansson, Kjell and Mortensen, Svend-Aage and Saunamaki, Kari and Simonsen, Svein and Gude, Einar and Bendz, Björn and Solbu, Dag and Aukrust, Pål and Gullestad, Lars}},
  issn         = {{1534-6080}},
  language     = {{eng}},
  pages        = {{235--243}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Transplantation}},
  title        = {{Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial.}},
  url          = {{http://dx.doi.org/10.1097/TP.0b013e31822057f1}},
  doi          = {{10.1097/TP.0b013e31822057f1}},
  volume       = {{92}},
  year         = {{2011}},
}