A new clinical trial presented at the American Heart Association’s Scientific Sessions 2025 shows that the cholesterol-lowering medication alirocumab, a PCSK9 inhibitor, combined with a statin can reduce LDL cholesterol levels by more than 50% in patients after a heart transplant. The findings, simultaneously published in the journal Circulation, support more aggressive cholesterol management for this high-risk population.
The study, called CAVIAR (Cardiac Allograft Vasculopathy Inhibition with AliRocumab), tested the safety and effectiveness of adding alirocumab to a statin regimen among 114 adults who had recently undergone 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. The average age of participants was 58 years.
After one year, the average LDL cholesterol levels in the alirocumab group decreased from 72.7 mg/dL at enrollment to 31.5 mg/dL, a reduction of more than 50%. In the placebo group, average LDL levels remained unchanged at about 69.0 mg/dL. However, the trial did not find a significant reduction in cardiac allograft vasculopathy (CAV), a progressive coronary artery disease that is a leading cause of death after heart transplant. Coronary artery plaque volume increased numerically in both groups, but there was no statistically significant difference between the alirocumab and placebo groups.
“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, 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.”
High LDL cholesterol is a known risk factor for cardiovascular issues, including heart attack and stroke, according to the American Heart Association. For heart transplant recipients, CAV is a common complication that causes narrowing and blockage of coronary arteries. Statins are typically used to manage cholesterol levels after transplant, but they often fall short of achieving target 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 more stringent targets for those with pre-existing conditions.
The study had some limitations, including less plaque progression than expected in both groups and low baseline LDL levels in the placebo arm, which reduced the study’s power to detect a difference. Researchers noted that larger trials with longer follow-up are needed to confirm whether PCSK9 inhibitors can reduce CAV development.
The trial was conducted at Stanford Medical Center and Kaiser Permanente in Santa Clara, California, starting in 2019. All participants underwent additional screening procedures to evaluate blood flow and plaque buildup in their coronary arteries at enrollment and one year after transplant. No significant side effects were observed in either group.
For more information on cholesterol management, visit the American Heart Association’s Prevention and Treatment of High Cholesterol page. The full abstract is available in the American Heart Association Scientific Sessions 2025 Online Program Planner.
