Dyslipidemia and therapies after heart transplantation: Current evidence and future directions

Dyslipidemia following orthotopic heart transplantation (OHT) affects up to 80% of transplant recipients, contributing to both atherosclerotic cardiovascular disease and cardiac allograft vasculopathy (CAV), a leading cause of late graft failure and mortality. As transplant rates and post-OHT survival continue to rise, understanding and managing dyslipidemia in this population is of increasing clinical importance.

This state-of-the-art review draws upon clinical trials, retrospective analyses, observational studies, pharmacokinetic studies, and leading international cardiovascular and transplant society guidelines.

Post-OHT dyslipidemia arises from traditional risk factors, including diet, obesity, diabetes, and genetic predisposition such as familial hypercholesterolemia, and is compounded by transplant-specific factors, most notably immunosuppressive (IS) medications. IS medications further contribute to lipid abnormalities through low-density lipoprotein cholesterol (LDL-C) receptor downregulation, lipoprotein lipase inhibition, and insulin resistance induction. Statins remain the cornerstone of therapy, reducing CAV incidence, rejection, and mortality through both lipid-lowering and pleiotropic immunomodulatory mechanisms, though drug interactions necessitate careful selection and dose limitation. Nonstatin adjunct therapies vary in their suitability, with select agents demonstrating favorable efficacy and safety profiles, while others carry significant interaction risks with IS medications. Emerging therapies, including bempedoic acid, siRNA therapeutics, and LDL-C apheresis show promise but require further study.

Effective post-OHT dyslipidemia management requires individualized strategies accounting for transplant-specific pharmacology, drug interactions, and long-term graft outcomes. Future research should define optimal LDL-C targets and evaluate novel lipid-lowering agents in this population.