NEW ORLEANS — A clinical trial presented at the American Heart Association’s Scientific Sessions 2025 found that 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. The study, published simultaneously in the journal Circulation, tested the safety and effectiveness of adding alirocumab to rosuvastatin soon after transplant to prevent cardiac allograft vasculopathy (CAV), a progressive coronary artery disease and leading cause of death in transplant recipients.
“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 lead author William F. Fearon, M.D., FAHA, 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.”
The CAVIAR (Cardiac Allograft Vasculopathy Inhibition with AliRocumab) trial included 114 adults with a mean age of 58 years who had received heart transplants. Participants were enrolled within eight weeks after transplant and randomly assigned to receive either 150 mg of alirocumab or a placebo, both combined with rosuvastatin. After one year, average LDL cholesterol levels in the alirocumab group dropped from 72.7 mg/dL to 31.5 mg/dL, a decrease of more than 50%, while levels in the placebo group remained stable at around 69.0 mg/dL.
Despite the significant cholesterol reduction, the study found no statistically significant difference in the development of cardiac allograft vasculopathy between the two groups. Coronary artery plaque volume increased numerically in both groups from baseline to 12 months, but the change was minimal and not different between groups. The researchers noted that plaque progression was less than expected, and baseline LDL levels were low in the statin-only group, which reduced the study’s power to detect a difference.
High LDL cholesterol is a known risk factor for CAV, and statins are standard therapy after heart transplant. However, statins alone often fail to achieve target cholesterol levels. The American Heart Association recommends a “lower is better” approach for LDL cholesterol, with ideal levels below 100 mg/dL for healthy adults and below 70 mg/dL for those with cardiovascular disease or diabetes. The findings suggest that adding a PCSK9 inhibitor can help achieve these lower levels safely in transplant patients.
“Our study highlights the potential for more aggressive lipid management in this high-risk population,” said Fearon. “Further research with longer follow-up is needed to determine if this approach can ultimately reduce the burden of cardiac allograft vasculopathy.”
For more information on cholesterol management, visit the American Heart Association’s resources on Prevention and Treatment of High Cholesterol. Additional details on the study can be found in the Circulation manuscript.
