Effect of Everolimus Introduction on Cardiac Allograft Vasculopathy-Results of a Randomized, Multicenter Trial.
(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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https://lup.lub.lu.se/record/2007983
- author
- organization
- publishing date
- 2011
- 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<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.}}, 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}}, }