Author + information
- Received July 6, 2017
- Revision received December 4, 2017
- Accepted December 5, 2017
- Published online February 5, 2018.
- Rabea Asleh, MD, PhD, MHA,
- Alexandros Briasoulis, MD, PhD,
- Walter K. Kremers, PhD,
- Rosalyn Adigun, MD, PharmD,
- Barry A. Boilson, MD,
- Naveen L. Pereira, MD,
- Brooks S. Edwards, MD,
- Alfredo L. Clavell, MD,
- John A. Schirger, MD,
- Richard J. Rodeheffer, MD,
- Robert P. Frantz, MD,
- Lyle D. Joyce, MD, PhD,
- Simon Maltais, MD, PhD,
- John M. Stulak, MD,
- Richard C. Daly, MD,
- Jonella Tilford, BSc,
- Woong-Gil Choi, MD,
- Amir Lerman, MD and
- Sudhir S. Kushwaha, MD∗ ()
- Department of Cardiovascular Diseases and Health Sciences Research and the William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota
- ↵∗Address for correspondence:
Dr. Sudhir S. Kushwaha, Mayo Clinic, Department of Cardiovascular Diseases, 200 First Street SW, Gonda 5 S, Rochester, Minnesota 55905.
Background Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking.
Objectives The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT.
Methods A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies.
Results The progression in plaque volume (2.8 ± 2.3 mm3/mm vs. 0.46 ± 1.8 mm3/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT.
Conclusions Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.
- cardiac allograft vasculopathy
- coronary intravascular ultrasound
- heart transplantation
Dr. Kremers has received research funding from AstraZeneca, Biogen, and Roche. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 6, 2017.
- Revision received December 4, 2017.
- Accepted December 5, 2017.
- 2018 American College of Cardiology Foundation
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