Effect of everolimus introduction on cardiac allograft vasculopathy--results of a randomized, multicenter trial.

Arora, Satish; Ueland, Thor; Wennerblom, Bertil; Sigurdardottir, Vilborg; Eiskjær, Hans; Bøtker, Hans E; Ekmehag, Bjorn; Jansson, Kjell; Mortensen, Svend-Aage; Saunamaki, Kari; Simonsen, Svein; Gude, Einar; Bendz, Bjørn; Solbu, Dag; Aukrust, Pål; Gullestad, Lars (2011). Effect of everolimus introduction on cardiac allograft vasculopathy--results of a randomized, multicenter trial. Transplantation, 92(2), pp. 235-243. Lippincott Williams & Wilkins 10.1097/TP.0b013e31822057f1

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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(3), 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Sigurdardottir, Vilborg

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0041-1337

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Vilborg Sigurdardottir

Date Deposited:

07 Mar 2016 09:29

Last Modified:

07 Mar 2016 09:29

Publisher DOI:

10.1097/TP.0b013e31822057f1

PubMed ID:

21677600

BORIS DOI:

10.7892/boris.76376

URI:

https://boris.unibe.ch/id/eprint/76376

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