PCSK9 inhibitors and their use in advanced heart failure and heart transplant recipients

The use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has garnered widespread attention in the medical community over the past ten years. A number of landmark trials have demonstrated the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein (LDL) levels dramatically when added to background statin therapy. Importantly, their use has led to a significant reduction in adverse events in patients at risk and with established cardiovascular diseases. Published evidence is sparse in the heart failure (HF) population, especially in those with Stage D disease. While the use of PCSK9 inhibitors has not been reported in patients with durable mechanical circulatory support devices, limited data exist in heart transplant recipients. Management of dyslipidemia is critically important in post-heart transplant population as it contributes to the development of cardiac allograft vasculopathy (CAV). However, most 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) interfere with the metabolism of commonly used immunosuppressant agents, such as tacrolimus. Case studies in post-heart transplant patients demonstrated significant LDL reduction with PCSK9 inhibitor use, without significant drug-drug interactions or adverse events. Two trials are currently underway examining their efficacy in reducing CAV progression. This paper aims to review the available clinical evidence for PCSK9 inhibitor use in HF patients, with specific focus on the advanced heart failure group.