PCSK9 Inhibition Lowers LDL Cholesterol After Heart Transplantation: An Updated Systematic Review and Meta-Analysis

Lipid management after heart transplantation (HT) is complicated by post-transplant dyslipidemia, immunosuppression, statin intolerance, and cardiac allograft vasculopathy (CAV). Proprotein convertase subtilisin/kexin Type 9 (PCSK9) inhibitors lower LDL-C in non-transplant populations, but HT recipients were under-represented in pivotal lipid trials. This updated systematic review and exploratory meta-analysis synthesized full-text evidence of PCSK9 inhibition after adult HT, predominantly with alirocumab or evolocumab. LDL-C lowering was the primary lipid outcome. CAV imaging/physiology, rejection, donor-specific antibodies, immunosuppression stability, and safety were secondary outcomes. PubMed/MEDLINE, Scopus, Cochrane Library, and Google Scholar were searched through June 20, 2026. Sixteen primary studies were included. Two independent randomized trials, EVOLVD and CAVIAR, both conducted during the first post-transplant year, provide the highest-quality evidence. The remaining evidence consists of an EVOLVD physiology/OCT substudy and observational or case-based reports. Ten studies contributed LDL-C effect and variance data. The exploratory random-effects summary estimated an LDL-C reduction of 73.6 mg/dL (95% CI, 58.8-88.4, I² = 89.8%). The randomized-trial subgroup showed a smaller but consistent reduction of 41.8 mg/dL (95% CI, 35.9-47.7). Observational estimates were larger but derived from selected, lower-certainty cohorts. Randomized first-year evidence did not show clear improvement in CAV imaging or coronary physiology. PCSK9 inhibition lowers LDL-C after HT and appears tolerable, but CAV modification and graft-outcome benefit remain unproven.