Dr. William F. Fearon and Dr. C. Michael Gibson Discuss CAVIAR: Can Alirocumab Curb Cardiac Allograft Vasculopathy After Transplant?

In this SnackableHealth edition, Dr. William Fearon joins Dr. C. Michael Gibson live from AHA 2025 to unpack the CAVIAR trial — a NIH-funded, double-blind, randomized, placebo-controlled study testing whether adding alirocumab (a PCSK9 inhibitor) to standard therapy could slow the development of cardiac allograft vasculopathy (CAV) within the first year after heart transplantation. The trial enrolled 114 recipients, all placed on high-intensity rosuvastatin early post-transplant — a noteworthy departure from the usual low-dose or pravastatin regimens often chosen for safety concerns in this population.

Before randomization, every participant underwent a comprehensive baseline evaluation: coronary angiography, near-infrared spectroscopy IVUS to assess plaque volume and composition, coronary physiology (FFR, CFR, IMR), endothelial testing with acetylcholine, and biomarker panels including CRP, Lp(a), and ApoB. The primary endpoint was change in plaque volume by IVUS from baseline to one year.

Now, the executive summary: safety—check. Alirocumab was well tolerated, with no safety concerns compared to placebo. Metabolic execution—stellar. Mean baseline LDL hovered around 70 mg/dL in both arms (thanks to rosuvastatin), dropping to ~35 mg/dL with alirocumab and remaining unchanged with placebo. CRP levels held steady, while Lp(a) and ApoB fell more sharply with alirocumab — biologically encouraging signals that may translate into longer-term benefit. The structural story, however, stayed flat: no significant difference in plaque volume progression between groups. Interestingly, neither arm showed the steep plaque increase seen in older cohorts — likely a testament to aggressive lipid control and modern transplant care. Physiologic indices stayed normal and stable across both arms.

As Dr. Fearon emphasized, alirocumab proved safe and potent for LDL reduction even in complex post-transplant regimens involving immunosuppressants. Dr. Gibson pointed out the mechanistic nuance — while statins address both lipid and inflammation (CRP), PCSK9 inhibitors are LDL specialists with less anti-inflammatory reach, which might limit their impact on CAV’s immune-inflammatory substrate.

Exploratory subgroup analyses hinted at potential benefits among older patients, those with above-median LDL, and those with higher baseline apolipoprotein A, suggesting that a longer follow-up or enriched high-risk cohort might reveal structural advantages not captured within one year.

Bottom line: CAVIAR de-risks alirocumab use after cardiac transplantation — proving it’s safe, highly effective at LDL lowering, and compatible with immunosuppressive therapy. Yet, in a heavily statin-treated population with already low LDL, structural benefits didn’t materialize within 12 months. For now, it’s a strong green light for PCSK9 inhibitors when statins alone aren’t enough, and a call for future, longer, higher-risk studies to see if these biochemical wins can become anatomical ones.