Lipid Management in Renal Transplant Recipients Using Evolocumab.

Cardiovascular disease is the leading cause of death in renal transplant recipients (RTR). 44% of RTR have LDL-C greater than 100mg/dL, six months after transplant. The correlation between the increase in serum LDL level and the increased risk of atherosclerotic cardiovascular disease (ASCVD) is well established. A reduction in LDL level is associated with a decreased risk of mortality and morbidity in patients with ASCVD. Statins have been the long-standing drug of choice in treating dyslipidemia. A single prospective randomized trial known as the ALERT trial compared the benefits of statins to placebo in transplant recipients. The original study consisted of 2000 RTR and an extension of this study evaluated 1652 patients and demonstrated a 21% reduction in major cardiac events (p=0.036) and a 29% reduction in cardiac death or definite non-fatal myocardial infarction (p=0.014). Even though statins decrease the probability of cardiovascular events there was no difference in graft survival or mortality benefit in RTR. Another concerning factor for the use of statins is the tolerability of these drugs. Statins have been associated with hepatotoxicity and myotoxicity, the incidence of which is higher in RTR. This effect is dose-related and may be precipitated by the administration of agents that inhibit cytochrome p450 isoenzymes such as Tacrolimus and Cyclosporine which are the most commonly used immunosuppressants. Another statin based drug (Fluvastatin) has been associated with proteinuria and renal failure. Hence there is a need to explore novel treatment options in the management of dyslipidemia, particularly in RTR. PCSK-9 inhibitors (Proprotein Convertase Subtilisin Kinase-9 inhibitors) have shown to decrease LDL levels by 60% in patients on statin therapy. However, these drugs have been studied sparingly in patients with Chronic Kidney Disease (CKD) and have not yet been analyzed in RTR.

The study will involve 120 patients across 3 different hospitals. Two different but equivalent drug dosing strategies are available. A 420mg monthly subcutaneous injection using an on-body infusor (Repatha Pushtronex system) or a 140mg subcutaneous injection once every two weeks using a prefilled auto-injector (Repatha SureClick). The choice of dosing strategy will be based on patient preference. This study will be conducted over one year.

Inclusion criteria

• Adult renal transplant recipients greater than 1-year post-transplantation, men and women between 18 and 85 years of age, inclusive.
• Any patient with documented ASCVD or diabetes and 1 or more risk factors for ASCVD, including, but not limited to obesity, inactive lifestyle, hypertension, smoking, and family history. and an LDL >70 mg/dl (Highest-Risk Patients)
• Any patient not classified as one of our highest-risk patients, that has an LDL >100 mg/dl

Exclusion criteria

• Patients currently enrolled in another interventional clinical trial.
• Patients being actively treated for cellular or antibody-mediated rejection.
• Serious hypersensitivity to Evolocumab or any component of the formulation.
• Patients who are pregnant or planning a pregnancy in the next one year.