Lipid-lowering agents in solid organ transplant recipients

Abstract

Although pre- and post-transplant dyslipidaemia is one of the most prevalent modifiable risk factors associated with an increased risk of major cardiovascular events, it remains underdiagnosed and undertreated. Moreover, the risk of cardiovascular events, acute allograft rejection and vasculopathy associated with dyslipidaemia is underestimated. Although the most prominent underlying cause of dyslipidaemia in solid organ transplant (SOT) recipients is immunosuppressants, their adjustment should be done with caution to avoid an acute graft rejection. Dietary intervention and lipid-lowering therapy (LLT) are needed to lower low-density lipoprotein cholesterol (LDL-C) and triglycerides and to improve the outcomes. Although statins are first-line drugs, non-adherence, interactions with immunosuppressants and the concern related to polypharmacy impact statin use in SOT patients. The evolving evidence on combination therapy with statin and ezetimibe, novel PCSK9 modulators and bempedoic acid indicate that LDL-C can be safely and efficiently reduced with improved adherence. Since SOT patients are complex, a structured multidisciplinary team approach can deliver comprehensive lipid management, improve patient care and prevent potential complications. A call to action is needed for further trials and registries to determine potential benefits of strategy based on initial combination therapy with ezetimibe and a low/moderate dose of statin, as well as novel LLT. Optimal lipid treatment targets in SOT recipients should be determined, depending on the transplanted organ and cardiovascular risk category. We aimed to review current and future management of lipid disorders, propose an algorithm useful in clinical practice and call attention to broader use of novel LLTs along with further studies to assess their impact on clinical outcomes.

Keywords: PCSK9 inhibitors; dyslipidaemia; ezetimibe; solid organ transplantation; statins.

Figure 1:

Management of hypercholesterolaemia in SOT recipients. (a) TG >400 mg/dl: measure direct LDL-C. (b) LDL-C >190 mg/dl: IS evaluation, TLC and statin initiation; LDL-C 115–189 mg/dl in a high- or very-high-risk patient: IS evaluation, TLC 3 months, after 3 months of TLC when LDL-C is >100 mg/dl initiate statin treatment; TG >500 mg/dl: IS evaluation (GC, mTOR inhibitor), diet evaluation, exclude alcohol use, diabetes, kidney failure (GFR, proteinuria). (c) Consider switching CsA to tacrolimus or reducing the CsA dose, adding/increasing the dose of mycophenolate mofetil, withdrawal of or reducing the doses of corticosteroids and mTOR inhibitors (when TG >500 mg/dl). TLC: therapeutic life changes; CK: creatine kinase.

Figure 2:

Management of statin-associated muscle symptoms in SOT recipients. CK: creatine kinase.