NEW ORLEANS — The cholesterol-lowering medication alirocumab, a PCSK9 inhibitor, combined with a statin reduced LDL cholesterol levels by more than 50% in patients after a heart transplant, according to a late-breaking science presentation at the American Heart Association’s Scientific Sessions 2025. The results, published simultaneously in the journal Circulation, also showed that the combination did not significantly reduce the development of cardiac allograft vasculopathy (CAV), a progressive coronary artery disease common after transplant.
“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 Dr. William F. Fearon, a professor of medicine and chief of interventional cardiology at Stanford University School of Medicine. “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.”
In the CAVIAR (Cardiac Allograft Vasculopathy Inhibition with AliRocumab) trial, researchers tested the safety and effectiveness of adding alirocumab to a statin regimen in patients soon after a heart transplant to prevent CAV. The study included 114 adults with a mean age of 58 years who had received a heart transplant. Participants were enrolled within eight weeks after transplant and randomly assigned to receive either 150 mg of alirocumab plus rosuvastatin or a placebo plus rosuvastatin. One year post-transplant, the average LDL cholesterol levels in the alirocumab group decreased from 72.7 mg/dL to 31.5 mg/dL, a reduction of more than 50%, while the placebo group’s levels remained stable at around 69.0 mg/dL.
Despite the significant cholesterol reduction, coronary artery plaque volume increased numerically in both groups from baseline to 12 months, and there was no significant difference in plaque progression or in the incidence of CAV between the groups. No significant side effects were reported in either group. The researchers noted that the study was limited by less plaque progression than expected and low baseline LDL levels in the placebo group, which reduced the power to detect a difference.
According to the American Heart Association, high LDL cholesterol is a major risk factor for cardiovascular events. For healthy adults, an LDL level below 100 mg/dL is considered ideal, and for those with pre-existing conditions, targets are more stringent, often below 70 mg/dL. The study suggests that while aggressive cholesterol management with a PCSK9 inhibitor is safe and effective in lowering LDL after heart transplant, it may not be sufficient to prevent CAV alone. Further research with longer follow-up and larger populations is needed to determine if such therapy can ultimately reduce the burden of CAV.
The trial was conducted at Stanford Medical Center and Kaiser Permanente in Santa Clara, California, and was funded by Sanofi and Regeneron Pharmaceuticals, the manufacturers of alirocumab. The full manuscript is available in Circulation.
