Abstract Body (Do not enter title and authors here): Background:
Cardiac allograft vasculopathy (CAV) remains a primary driver of long-term mortality following heart transplantation (HT). While dyslipidemia is a known contributor, lipid management with statins is often suboptimal. This study aims to elucidate the safety and potential benefit of adding a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy early after HT for preventing the development of early CAV.
Methods:
The CAVIAR trial is a prospective, multicenter, double-blind, randomized trial funded by the NIH. Within 8 weeks of HT, participants were randomized to receive either alirocumab or placebo, on top of rosuvastatin and standard of care. Immediately prior to randomization and at one year, all participants underwent invasive coronary assessment, including angiography, endothelial function testing (acetylcholine), coronary physiology (FFR, CFR, and IMR), and intravascular ultrasound with near-infrared spectroscopy (NIRS-IVUS). Lipid values, including lipoprotein(a) [Lp(a)] were assessed at baseline and at prespecified intervals. The primary endpoint is the change in coronary artery plaque volume from baseline to one year post-HT, as independently assessed by a core laboratory. Key secondary endpoints include the safety of PCSK9 inhibition early after HT and changes in lipid levels and other biomarker values, coronary physiologic parameters, endothelial function, and lipid content of coronary plaque as assessed by spectroscopy.
Results:
A total of 113 HT recipients (mean age: 57.8±12.1 years) were randomized. The final participant will complete one-year follow-up in August, 2025. If accepted for presentation, we will present the primary and secondary endpoints as described above.
Conclusion:
The multicenter, randomized, double-blind CAVIAR trial is expected to provide valuable data regarding the safety and efficacy of PCSK9 inhibition early after heart transplantation. By incorporating comprehensive assessments of coronary physiology and plaque composition, this trial may offer crucial mechanistic insights into the benefits of aggressive lipid-lowering therapy in transplant recipients.