Cardiac Allograft Vasculopathy Inhibition With Alirocumab: The CAVIAR Trial.
Fearon, W. F., et al.Circulation. 2026 Jan 6;153(1):7-17.
Aims
The aim of the study was to examine whether the addition of proprotein convertase subtilisin/ kexin 9 (PCSK9) inhibitor alirocumab to standard statin therapy early after heart transplantation safely lowered cholesterol and reduced progression of cardiac allograft vasculopathy.
Interventions
Participants were randomised to either alirocumab therapy or placebo.
Participants
114 heart transplant recipients (≥18 years).
Outcomes
The primary outcome was change in plaque volume. Th secondary outcomes were differences between arms in low-density lipoprotein cholesterol (LDL-C) and other lipid particle values, coronary physiology and other near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) parameters.
Follow-up
1 year
CET Conclusions
Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Dyslipidaemia with elevated LDL cholesterol (LDL-C) contributes to the development of CAV following HT and patients are routinely administered statin therapy to reduce LDL-C. Alirocumab is a proprotein convertase subtilisin/Kexin 9 inhibitor which is used as second-line therapy for dyslipidaemia in patients with elevated atherogenic lipoproteins despite statin treatment. This randomised control trial investigated the efficacy of Alirocumab in patients following HT. 114 patients were randomised to either statin and Alirocumab therapy or statin therapy alone. The primary outcome was change in plaque volume at one year following HT (as assesses by intravascular ultrasound). Secondary outcomes included change in LDL-C level and coronary flow physiology. LDL-C levels were significantly lower in the Alirocumab group, but neither plaque progression nor coronary flow physiology were improved in the treatment group. The authors attribute this lack of clinical effect to patient selection – the average baseline LDL-C in both groups was low (approximately 70mg/dl). A sub-group analysis showed clinical benefit in patients with higher LDL-C and more advanced plaque at baseline. Similarly, when Alirocumab was investigated in patients with ischaemic heart disease, a treatment effect was only found in patients with a baseline LDL-C greater than 100mg/dl. Taken together, these data suggest that, similar to the general population, Alirocumab in HT should be reserved for second-line therapy in patients with statin resistant dyslipidaemia.
Data analysis
Strict intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT03537742