Randomized Trial of Cholesterol Lowering With Evolocumab for Cardiac Allograft Vasculopathy in Heart Transplant Recipients.

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. (Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-novo Heart Transplant Recipients [EVOLVD]; NCT03734211).
Competing Interests: Funding Support and Author Disclosures This work was funded by Amgen, the South-Eastern Norway Regional Health Authority, and the Kardimmun foundation. Amgen provided the investigational medicinal products and an unrestricted grant. The funders had no role in the trial design or data collection, analysis, and interpretation. The funders had no role in the preparation or review of the manuscript, or in the decision to publish, but were allowed to read the manuscript for approval prior to publication. Dr Broch has received lecture fees from Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Novo Nordisk, Orion Pharma, Pfizer, Pharmacosmos, and Vifor Pharma. Dr Gullestad has received lecture fees from AstraZeneca, Boehringer Ingelheim, Novartis, and Amgen; and has been a member of local advisory board in AstraZeneca and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)