Cardiac Allograft Vasculopathy Inhibition with Alirocumab:The CAVIAR Trial

Background: Cardiac allograft vasculopathy (CAV) is an important cause of mortality after heart transplantation (HT). Dyslipidemia is a major contributor to the development of CAV. The safety and effectiveness of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibition to lower cholesterol and prevent CAV early after HT is not well-established. Methods: In this investigator-initiated, prospective, multicenter, double-blind, randomized trial, participants were randomized early after HT to receive either alirocumab or placebo, in addition to rosuvastatin. Prior to randomization and at one year, all participants underwent invasive coronary assessment, including angiography, fractional flow reserve (FFR), coronary flow reserve (CFR), the index of microcirculatory resistance (IMR), and intravascular ultrasound with near-infrared spectroscopy (NIRS-IVUS). Lipid values were assessed at baseline and at prespecified intervals. The primary endpoint was the change in coronary artery plaque volume from baseline to one year post HT based on serial IVUS. Results: A total of 114 HT recipients were included (57 assigned to alirocumab and 57 assigned to placebo). Baseline characteristics were well matched between the two groups. The low density lipoprotein cholesterol (LDL-C) levels decreased significantly from baseline to one year in the alirocumab arm (72.7 ±31.7 to 31.5 ±20.7 mg/dL, p<0.001) and did not change with placebo (69.0 ±22.4 to 69.2 ±28.1 mg/dL, p=0.92). Plaque volume increased numerically in both groups from baseline to 12 months (alirocumab 176.3 ±95.2 to 184.5 ±105.4 mm ³ , p=0.23; placebo 173.7 ±96.7 to 183.1 ±109.8 mm ³ , p=0.15). The change in plaque volume (mean difference in differences) did not differ between groups (1.01 (0.89-1.14), p=0.86). FFR, CFR and IMR did not change significantly with the addition of alirocumab. There were no significant adverse events related to alirocumab. Conclusions: PCSK9 inhibition with alirocumab in addition to statin therapy early after HT safely lowers LDL-C, but did not reduce coronary artery plaque progression after one year compared with rosuvastatin alone, in patients with a low baseline LDL-C.