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Title: PCSK9 inhibitors in advanced heart failure and heart transplant recipients
Authors: Arianne C. Agdamag1, Valmiki R. Maharaj1, Megan Fraser1, Jonathan B. Edmiston2, Victoria Charpentier2, Garry S. Francis1, Tamas Alexy1
Affiliations: 1Department of Medicine, Division of Cardiology, University of Minnesota, Minneapolis, MN 55455, USA.
2Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Abstract: The use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has garnered widespread attention in the research community over the past ten years. A number of landmark trials have demonstrated the efficacy of PCSK9 inhibitors in dramatically lowering low density lipoprotein (LDL) levels when they are added to statin therapy. Importantly, their use has led to a significant reduction in adverse events in patients at risk and with established cardiovascular diseases (CVD). Published evidence is sparse, however, in the heart failure (HF) population, especially in the group with Stage D disease. While the use of PCSK9 inhibitors has not been reported in patients with durable mechanical circulatory support devices, limited data do exist in heart transplant recipients. Management of dyslipidemia is critically important in this population as it contributes to the development of cardiac allograft vasculopathy (CAV). However, most HMG-CoA reductase inhibitors (statins) interfere with the metabolism of commonly used immunosuppressant agents, such as tacrolimus. Case studies in post-heart transplant patients have demonstrated significant LDL reduction with PCSK9 inhibitor use but without significant drug-drug interactions or adverse events. Two trials are currently underway with the goal to examine 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 population with advanced heart failure.