CAVIAR: Alirocumab Safely Lowers Cholesterol After Heart Transplant

A cholesterol-lowering regimen that combines PCSK9 inhibitor alirocumab with statin therapy safely reduced low-density lipoprotein cholesterol (LDL-C) levels by more than 50% in adults early after heart transplantation, according to new data from the CAVIAR trial.¹

However, the study did not meet its primary end point for plaque progression. Late-breaking findings were presented at the American Heart Association (AHA) 2025 Scientific Sessions by William Fearon, MD, professor of cardiovascular medicine at Stanford University School of Medicine, and published simultaneously in the AHA’s journal Circulation.²

LDL-C Levels Dropped at 1 Year

The National Institutes of Health–funded CAVIAR—Cardiac Allograft Vasculopathy Inhibition with AliRocumab—trial included 114 adults within 6 months of heart transplantation to assess whether adding alirocumab to rosuvastatin could prevent the development of cardiac allograft vasculopathy (CAV), a leading cause of death among transplant recipients. Participants were randomized 1:1 to receive either alirocumab or placebo alongside rosuvastatin.

After 1 year of treatment, LDL-C levels fell by more than 50% in the alirocumab group, dropping from 72.7 mg/dL at baseline to 31.5 mg/dL, but levels stayed the same in the placebo arm (69.0 mg/dL to 69.2 mg/dL). Despite this notable reduction with alirocumab, no significant difference in plaque progression was observed between treatment arms (P = .86). Neither group experienced major adverse events or notable plaque progression overall, suggesting both regimens were safe and well tolerated.

Fearon noted that participants in both arms had lower-than-expected baseline LDL-C levels around 70 mg/dL.¹ “This was lower than we anticipated and lower than previous studies had shown, and I think a reflection of the aggressive statin therapy that our participants received in the study,” he explained at AHA 2025.

Clinical Implications for CAVIAR

CAV is a form of accelerated coronary atherosclerosis that affects up to half of transplant recipients within 10 years, often driven by dyslipidemia and immune-related injury to the vessel walls. Although prior data have shown treatments like alirocumab and evolocumab can lower LDL-C in this patient population, short-term benefits on plaque morphology or coronary physiology are unclear.

“Dyslipidemia is a major contributor to the development of CAV,” Fearon explained. “The safety and efficacy of PCSK9 inhibition to lower cholesterol and prevent CAV early after heart transplantation is not well-established.”

Amanda R. Vest, MBBS, MPH, FAHA, director of the Cardiac Transplant Program at Tufts Medical Center, praised the trial’s rigor despite its challenges. “It’s incredibly difficult to do randomized controlled trials in this niche population,” she said. Vest emphasized that CAV risk is multifactorial—depending on both donor and recipient factors—and that hyperlipidemia management addresses only 1 of several potential contributors.

“At the end of the day, the contributions towards development of CAV in our heart transplant patients from the traditional risk factors such as hyperlipidemia may be fairly modest,” Vest said. “Although we want to optimize metabolic health to help our patients survive and thrive, maybe a simple lowering of LDL, at least in the short term, is not going to have a huge impact.”

Fearon noted that longer-term follow-up and larger patient populations are needed to determine whether PCSK9 inhibition can meaningfully influence clinical outcomes such as graft survival or mortality. He and Vest also highlighted the need for continued exploration of metabolic and inflammatory pathways in reducing posttransplant cardiovascular risk, including potential roles for glucagon-like peptide 1 receptor agonists.

References

1. Fearon WF. Cardiac allograft vasculopathy inhibition with alirocumab: the CAVIAR trial. Presented at: AHA 2025 Scientific Sessions; November 10, 2025; New Orleans, LA.
2. Fearon WF, Terada K, Takahashi K, et al. Cardiac allograft vasculopathy inhibition with alirocumab: the CAVIAR trial. Circulation. Published online November 10, 2025. doi:10.1161/CIRCULATIONAHA.125.077603