Immunologic Response to PCSK9 Inhibitors in Orthotopic Heart Transplant Recipients: A Case Series

Abstract

Introduction Coronary allograft vasculopathy (CAV) is implicated in a large subset of orthotopic heart transplant recipients with primary graft failure. Until recently, pharmacologic therapy for CAV prevention has been based around HMG-CoA reductase inhibitors. Given their drug-drug interactions with immunosuppressive therapy, often leading to elevations in creatine kinase and intolerable myalgias, tolerance to therapy has been poor. Although proprotein convertase subtilisin-kexin type 9 inhibitors have been shown to be a viable alternative in patients refractory to traditional lipid lowering therapy, these medications have not been studied in the heart transplant population. Being monoclonal antibodies, a concern that has been cited is the potential for these agents to induce an immunologic response that may ultimately compromise the graft. Methods Here we present a case series of three patients who are status-post orthotopic heart transplant with dyslipidemia and have been previously intolerant to multiple statins due to subjective symptoms. Alirocumab (1 patient; 75mcg subcutaneously every 2 weeks) and evolocumab (2 patients; 140mg subcutaneously every 2 weeks) were initiated. Results There was an average LDL reduction of 101 mg/dL. Donor specific antibodies were checked at least 1 month after initiation of therapy, all demonstrating no change from baseline. Furthermore, therapy was well tolerated with no patients reporting injection site reactions or other appreciable side effects. Conclusion In this case series of three post-orthotopic heart transplant recipients we were able to demonstrate the safe and effective use of PCSK9 inhibitors, without invoking a clinically significant immunologic response. Based on these results, we would advocate for larger scale trials aiming to assess CAV prevention and the potential immunologic impact of these agents.