Article Impact Level: HIGH Data Quality: STRONG Summary of Circulation https://doi.org/10.1161/CIRCULATIONAHA.125.077603 Dr. William F. Fearon et al.
Points
- The CAVIAR trial investigated alirocumab plus rosuvastatin for the early prevention of cardiac allograft vasculopathy post-heart transplantation.
- One hundred fourteen heart transplant recipients were randomized to either alirocumab or placebo, both co-administered with rosuvastatin.
- Alirocumab significantly reduced LDL-C from 72.7 to 31.5 mg/dL, while the placebo group showed no change.
- Coronary artery plaque volume numerically increased in both treatment arms by approximately 10 mm³, with no significant inter-group difference.
- PCSK9 inhibition with alirocumab effectively lowered LDL-C but did not demonstrate a reduction in coronary artery plaque progression after one year.
Summary
The investigator-initiated, prospective, multicenter, double-blind, randomized CAVIAR trial sought to evaluate the safety and efficacy of alirocumab, a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor, combined with rosuvastatin for the early prevention of cardiac allograft vasculopathy (CAV) following heart transplantation. CAV remains a critical driver of post-transplant mortality, with dyslipidemia recognized as a significant contributing factor. One hundred fourteen heart transplant recipients were randomized early post-transplant, allocating 57 to alirocumab and 57 to placebo, both alongside rosuvastatin therapy.
Participants underwent comprehensive invasive coronary assessments, including angiography, fractional flow reserve, coronary flow reserve, index of microcirculatory resistance, and intravascular ultrasound with near-infrared spectroscopy at baseline and at one year post-transplantation. Lipid profiles were also meticulously monitored. The primary endpoint focused on the change in coronary artery plaque volume from baseline to one year, quantified by serial intravascular ultrasound. Baseline characteristics were well-matched between the groups, ensuring robust comparative analysis.
Results demonstrated a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels in the alirocumab arm, decreasing from 72.7 ± 31.7 mg/dL to 31.5 ± 20.7 mg/dL (p < 0.001) over one year. Conversely, the placebo group showed no significant change in LDL-C (69.0 ± 22.4 mg/dL to 69.2 ± 28.1 mg/dL, p = 0.92). Despite this marked lipid lowering, plaque volume numerically increased in both groups (alirocumab: 176.3 ± 95.2 to 184.5 ± 105.4 mm³, p = 0.23; placebo: 173.7 ± 96.7 to 183.1 ± 109.8 mm³, p = 0.15). The mean difference in plaque volume change between the groups was 1.01 (0.89–1.14, p = 0.86), indicating no statistically significant difference. Furthermore, no significant changes were observed in functional coronary parameters, and no significant adverse events were reported. This suggests that while PCSK9 inhibition with alirocumab effectively lowers LDL-C, it did not significantly mitigate coronary artery plaque progression within the first year post-transplant.
Link to the article: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.077603
References
Fearon, W. F., Terada, K., Takahashi, K., Skoda, A., Luikart, H. I., Lamendola, C. A., Zimmermann, F. M., Hashikata, T., Saito, K., Yoshida, A., Varr, B., Knowles, J. W., Woo, C., Honda, Y., Teuteberg, J., & Khush, K. K. (2025). Cardiac allograft vasculopathy inhibition with alirocumab:the caviar trial. Circulation, CIRCULATIONAHA.125.077603. https://doi.org/10.1161/CIRCULATIONAHA.125.077603
