PCSK9 Inhibitor Combined with Statin Significantly Lowers Cholesterol in Heart Transplant Patients

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 compared to those taking a placebo plus statin, according to results from the CAVIAR clinical trial presented at the American Heart Association's Scientific Sessions 2025. The study, simultaneously published in the peer-reviewed journal Circulation, found that while the aggressive cholesterol management regimen was safe and effective at lowering LDL cholesterol, it did not reduce the risk of developing cardiac allograft vasculopathy (CAV), a progressive coronary artery disease that occurs after heart transplantation and remains a primary cause of death for many transplant recipients.

Researchers conducted the Cardiac Allograft Vasculopathy Inhibition with AliRocumab (CAVIAR) trial to test the safety and effectiveness of adding alirocumab to standard statin therapy in patients soon after heart transplantation. The study included 114 adults with a mean age of 58 years who had undergone heart transplants, with participants enrolled within eight weeks after transplantation and randomly assigned to receive either 150 mg of alirocumab with rosuvastatin or a placebo with rosuvastatin. Study author William F. Fearon, M.D., FAHA, a professor of medicine and chief of interventional cardiology at Stanford University School of Medicine, noted that treating heart transplant patients with this more aggressive cholesterol management approach was safe and significantly lowered LDL cholesterol levels.

After one year, participants in the alirocumab group experienced an average LDL cholesterol reduction from 72.7 mg/dL at enrollment to 31.5 mg/dL, representing a decrease of more than 50%. In contrast, the placebo group showed no statistically significant change from their baseline average of 69.0 mg/dL. Despite this substantial cholesterol reduction, coronary artery plaque volume increased numerically in both groups from baseline to 12 months, with no significant difference in plaque progression between the alirocumab and placebo groups. The study found minimal plaque progression in both groups and no significant side effects in either treatment arm.

The American Heart Association recommends a "lower is better" approach for cholesterol management, particularly for LDL-C levels, rather than targeting a single ideal number for all patients. For healthy adults, an LDL-C level below 100 mg/dL is considered ideal, while patients with pre-existing conditions like atherosclerotic cardiovascular disease or diabetes should aim for LDL-C levels of 70 mg/dL or lower. High LDL cholesterol, often called "bad" cholesterol, can lead to plaque buildup in arteries, increasing risk for cardiovascular events such as heart attacks and strokes, though it typically presents no symptoms itself.

Researchers acknowledged several study limitations, noting that because there was less plaque progression than expected in both groups and because LDL levels were already low at baseline in the rosuvastatin-alone arm, the study's power to detect a difference when adding alirocumab was reduced. Fearon emphasized that while these results support using PCSK9 inhibitors for patients with high LDL cholesterol levels in conjunction with statin therapy, more studies with longer-term follow-up and more participants are needed to determine if PCSK9 inhibitors can reduce the development of cardiac allograft vasculopathy. The trial was conducted by Stanford University starting in 2019, with transplant patients identified at Stanford Medical Center and Kaiser Permanente in Santa Clara, California. Additional information about the study is available in the full manuscript published in Circulation.