Safety of PCSK9 Inhibitors After Heart Transplantation Examined

In heart transplant recipients with suboptimal circulating low-density lipoprotein cholesterol (LDL-C) levels despite maximal tolerated statin doses, inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) may be associated with a substantial reduction in LDL-C and appears well tolerated.

In a case series published in the Canadian Journal of Cardiology, a total of 6 patients (median age, 55 years; interquartile range, 50.3-59.5 years) underwent PCSK9 inhibition and were assessed for safety and LDL-C-lowering efficacy.

In the case series, patients were treated with either tacrolimus or mycophenolate mofetil maintenance immunosuppression (n=3), tacrolimus and sirolimus for cardiac allograft vasculopathy (n=2), or prednisone plus cyclosporine plus mycophenolate mofetil (n=1).

Indications for PCSK9 inhibitor initiation included familial hypercholesterolemia (n=3) and statin intolerance (n=3). Additionally, one patient in the series had undergone kidney transplant within 19 years after an initial heart transplant.

Evolocumab was well tolerated in 100% of patients and was associated with no side effects or adverse events. During a median 9-month follow-up, no hospitalizations, episodes of infection, or rejection were reported. In addition, PCSK9 inhibition with evolocumab was associated with a >70% reduction in LDL-C, represented by mean pretreatment and posttreatment LDL-C levels of 4.5±1.2 mmol/L (179.9±45.8 mg/dL) and 1.28±0.9 mmol/L (49.6±33.3 mg/dL), respectively.

Limitations of the reported case series include its nonrandomized design as well as the small number of patients. According to the authors of the series, a randomized control trial (ClinicalTrials.gov Identifier: NCT3537742) is in the early stages of its enrollment period and will examine the efficacy and safety of PCSK9 inhibitors in heart transplantation recipients.

“Aggressive treatment of dyslipidemia in heart transplant recipients is important for prevention of systemic atherosclerosis and slowing progression of [cardiac allograft vasculopathy],” the authors wrote. “PCSK9 inhibitors are a potentially well tolerated and potent lipid-lowering therapeutic option for heart transplant patients with suboptimal LDL-C despite maximal tolerated statin doses.”

Disclosures: Joshua Knowles has received research grants from Amgen Inc. Please refer to original reference for full list of author disclosures.

Reference

Moayedi Y, Kozuszko S, Knowles JW, et al. Safety and efficacy of PCSK9 inhibitors after heart transplantation. Can J Cardiol. 2019;35(1):104.e1-104.e3.