In patients with low baseline LDL-C, early initiation of PCSK9 inhibition with alirocumab in addition to statin therapy following heart transplantation safely lowered LDL-C, but did not reduce coronary artery plaque progression after one year compared with rosuvastatin alone, based on findings from CAVIAR presented at AHA 2025 and simultaneously published in Circulation.

Researchers randomized 114 heart transplant recipients to either alirocumab or placebo, in addition to rosuvastatin. Before randomization and at one-year follow-up, participants underwent comprehensive invasive coronary evaluation, including angiography, fractional flow reserve (FFR), coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and intravascular ultrasound with near-infrared spectroscopy (NIRS-IVUS). Lipid levels were measured at baseline and at scheduled intervals. The primary endpoint was change in coronary artery plaque volume from baseline to one year after heart transplant.

Overall results found 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 and the change in plaque volume did not differ between groups, according to the researchers. In other findings, FFR, CFR and IMR did not change significantly with the addition of alirocumab and there were no significant adverse events related to alirocumab.

"Our study found treating patients who have had a heart transplant with a more aggressive cholesterol management regimen was safe and lowered their LDL-cholesterol levels significantly," said study author William Fuller Fearon, MD, FACC. "These results support PCSK9 inhibitors for patients who have high LDL cholesterol levels in conjunction with statin therapy, however, we need more studies testing treatment with PCSK9 inhibitors with longer term follow-up with more participants to confirm if PCSK9s can reduce the development of cardiac allograft vasculopathy."

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: AHA Annual Scientific Sessions, AHA25, Heart Failure