Impact of Evolocumab in Cardiac Transplant Patients With CAV

Phase 2

Completed

Brief Summary: Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (LDL) in patients who have not received a heart transplant. This drug works as a PCSK9-inhibitor. The primary objective of this study is to measure the impact of PCSK9-inhibitors on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline.

Detailed Description: Heart transplant remains the treatment of choice for patients with advanced heart failure. Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of the donor heart, and limits long term survival after transplant. The pathophysiology of CAV is complex and involves smooth muscle proliferation, inflammatory infiltrates, and lipid deposition. To date, only statin therapy has reduced CAV-related mortality. PCSK9 inhibitors are a new lipid lowering therapy shown to reduce cardiovascular clinical events in patients with coronary artery disease. We hypothesize that PCSK9 inhibition via evolocumab will significantly lower low density lipoprotein (LDL) and be well-tolerated in transplant patients with CAV. This phase II, open label, single center trial with enroll up to 40 heart transplant patients with CAV for treatment with evolocumab for one year. The primary outcome will be percent change in LDL at 12 weeks. Secondary outcomes will include change in CAV progression, impact of evolocumab on immunosuppression regimens and transplant rejection, and change in serum lipids after 52 weeks. Results of this study are intended to provide safety data in heart transplant patients with CAV and assess secondary outcomes including CAV progression and impact on immunosuppression and transplant rejection.

Recruitment & Eligibility

Inclusion Criteria

Heart transplant patients 19-80 years of age
Coronary allograft vasculopathy grade 1 or 2 documented by left heart cardiac catheterization
Able to provide signed informed consent

Exclusion Criteria

Cardiac allograft vasculopathy (CAV) grade 3
Rejection requiring IV therapy in the prior 3 months
Infection requiring IV therapy in the prior 3 months
Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal
Current or recent use of a PCSK9 inhibitor within the past 12 weeks
Organ transplant recipient other than heart
Renal dysfunction defined as glomerular filtration rate (GFR) < 20 ml/min
Known allergy to evolocumab or its components

Arm && Interventions

Group	Intervention	Description
Evolocumab	Evolocumab	Patients who will receive the study drug.

Primary Outcome Measures

Name	Time	Method
Percent Change in Serum LDL (mg/dL) After 12 Weeks of Evolocumab	12 weeks	The primary outcome measure for this study was percent change in LDL from baseline after 12 weeks of evolocumab therapy. Serum LDL was measured at baseline and after 12 weeks of evolocumab therapy. This primary endpoint was used in prior phase 2 trials investigating evolocumab in other patient populations. Wilcoxon matched-pairs signed rank test was used for statistical assessment.

Secondary Outcome Measures

Name	Time	Method

Locations (1): University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States

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