Randomized Trial of Cholesterol Lowering With Evolocumab for Cardiac Allograft Vasculopathy in Heart Transplant Recipients
(2024) In JACC: Heart Failure 12(10). p.1677-1688- Abstract
Background: Cardiac allograft vasculopathy is characterized by increased coronary intimal thickness and is a leading cause of death in heart transplant (HTx) recipients despite the routine use of statins. The experience with inhibitors of proprotein convertase subtilisin-kexin type 9 in HTx recipients is limited. Our hypothesis was that lowering cholesterol with the proprotein convertase subtilisin–kexin type 9inhibitor evolocumab would reduce coronary intimal thickness in these patients without compromising safety. Objectives: This double blind, randomized trial was conducted to test whether evolocumab reduces the burden of cardiac allograft vasculopathy. Methods: Patients who had received a cardiac allograft at 1 of the Nordic... (More)
Background: Cardiac allograft vasculopathy is characterized by increased coronary intimal thickness and is a leading cause of death in heart transplant (HTx) recipients despite the routine use of statins. The experience with inhibitors of proprotein convertase subtilisin-kexin type 9 in HTx recipients is limited. Our hypothesis was that lowering cholesterol with the proprotein convertase subtilisin–kexin type 9inhibitor evolocumab would reduce coronary intimal thickness in these patients without compromising safety. Objectives: This double blind, randomized trial was conducted to test whether evolocumab reduces the burden of cardiac allograft vasculopathy. Methods: Patients who had received a cardiac allograft at 1 of the Nordic transplant centers within the prior 4 to 8 weeks were randomized to monthly subcutaneous injections of evolocumab 420 mg or matching placebo. The primary endpoint was the baseline-adjusted maximal intimal thickness as measured by intracoronary ultrasound after 12 months’ treatment. Results: The trial enrolled 128 patients between June 2019 and May 2022. Matched pairs of coronary ultrasound images were available for 56 patients assigned to evolocumab and 54 patients assigned to placebo. At 12 months, the adjusted mean difference in the maximal intimal thickness between the 2 arms was 0.017 mm (95% CI: −0.006 to 0.040; P = 0.14). The mean reduction in low-density lipoprotein cholesterol with evolocumab compared with placebo was 1.11 mmol/L (95% CI: 0.86-1.37 mmol/L). The use of evolocumab was not associated with an increase in adverse events. Conclusions: Twelve months of treatment with evolocumab substantially reduced low-density lipoprotein cholesterol but did not reduce maximal coronary intimal thickness in HTx recipients.
(Less)
- author
- organization
- publishing date
- 2024-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cardiac allograft vasculopathy, cholesterol, heart transplant, randomized clinical trial
- in
- JACC: Heart Failure
- volume
- 12
- issue
- 10
- pages
- 12 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:38934968
- scopus:85198322782
- ISSN
- 2213-1779
- DOI
- 10.1016/j.jchf.2024.04.026
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2024 The Authors
- id
- fbaa2bd1-6c56-4132-9dd6-1b1da2c45b63
- date added to LUP
- 2024-11-27 11:32:00
- date last changed
- 2025-07-10 06:15:27
@article{fbaa2bd1-6c56-4132-9dd6-1b1da2c45b63,
abstract = {{<p>Background: Cardiac allograft vasculopathy is characterized by increased coronary intimal thickness and is a leading cause of death in heart transplant (HTx) recipients despite the routine use of statins. The experience with inhibitors of proprotein convertase subtilisin-kexin type 9 in HTx recipients is limited. Our hypothesis was that lowering cholesterol with the proprotein convertase subtilisin–kexin type 9inhibitor evolocumab would reduce coronary intimal thickness in these patients without compromising safety. Objectives: This double blind, randomized trial was conducted to test whether evolocumab reduces the burden of cardiac allograft vasculopathy. Methods: Patients who had received a cardiac allograft at 1 of the Nordic transplant centers within the prior 4 to 8 weeks were randomized to monthly subcutaneous injections of evolocumab 420 mg or matching placebo. The primary endpoint was the baseline-adjusted maximal intimal thickness as measured by intracoronary ultrasound after 12 months’ treatment. Results: The trial enrolled 128 patients between June 2019 and May 2022. Matched pairs of coronary ultrasound images were available for 56 patients assigned to evolocumab and 54 patients assigned to placebo. At 12 months, the adjusted mean difference in the maximal intimal thickness between the 2 arms was 0.017 mm (95% CI: −0.006 to 0.040; P = 0.14). The mean reduction in low-density lipoprotein cholesterol with evolocumab compared with placebo was 1.11 mmol/L (95% CI: 0.86-1.37 mmol/L). The use of evolocumab was not associated with an increase in adverse events. Conclusions: Twelve months of treatment with evolocumab substantially reduced low-density lipoprotein cholesterol but did not reduce maximal coronary intimal thickness in HTx recipients.</p>}},
author = {{Broch, Kaspar and Lemström, Karl B. and Gustafsson, Finn and Eiskjær, Hans and Karason, Kristjan and Gjesdal, Grunde and Fagerland, Morten W. and Pentikainen, Markku and Lommi, Jyri and Gude, Einar and Andreassen, Arne K. and Clemmensen, Tor S. and Christiansen, Evald H. and Bjørkelund, Elisabeth and Berg, Erlend S. and Arora, Satish and Gullestad, Lars}},
issn = {{2213-1779}},
keywords = {{cardiac allograft vasculopathy; cholesterol; heart transplant; randomized clinical trial}},
language = {{eng}},
number = {{10}},
pages = {{1677--1688}},
publisher = {{Elsevier}},
series = {{JACC: Heart Failure}},
title = {{Randomized Trial of Cholesterol Lowering With Evolocumab for Cardiac Allograft Vasculopathy in Heart Transplant Recipients}},
url = {{http://dx.doi.org/10.1016/j.jchf.2024.04.026}},
doi = {{10.1016/j.jchf.2024.04.026}},
volume = {{12}},
year = {{2024}},
}