Lipoprotein Apheresis in Refractory Angina Study

Study Overview
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Brief Summary
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The goal of this study is to determine the impact of apheresis on clinical parameters and symptoms of patients with refractory angina and raised Lp(a). The investigators will conduct a prospective, randomised controlled crossover study of 20 patients with refractory angina and raised Lp(a), randomised to undergoing lipoprotein apheresis weekly for three months or sham apheresis weekly for three months with assessment of myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, exercise capacity, angina symptoms and quality of life at the beginning and end of treatment. Patients will then crossover to the opposite study arm with the protocol repeated. The hypothesis is that the above parameters will be improved by lipoprotein apheresis in patients with raised Lp(a) and Refractory Angina. Investigators will also test for the genotypic presence of apolipoprotein(a) gene (LPA) locus variants (rs10455872 and rs3798220) which are thought to be associated with an increased level of Lp(a) and an increased risk of coronary disease.

Detailed Description
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Angina which is refractory to conventional medical therapy and revascularisation is challenging to manage. Lipoprotein(a) or Lp(a) is a genetically determined form of LDL-cholesterol, elevation of which is an independent risk factor and predictor of adverse cardiovascular events. Lp(a) is felt to increase cardiovascular risk via its prothrombotic effect and by enhancing intimal lipoprotein deposition. Lipoprotein apheresis is the most effective treatment for raised Lp(a). Lipid lowering agents such as statins have little to no effect on Lp(a) levels.

Official Title
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Clinical Outcomes, Perfusion and Vascular Function in Patients With Refractory Angina and Raised Lipoprotein (a), Treated With Lipoprotein Apheresis

Conditions
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Refractory Angina, Raised Lipoprotein(a)>50mg/dL or >500mg/L

Intervention / Treatment
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* Other: Lipoprotein Apheresis
* Other: Sham Apheresis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with refractory angina for more than three months. Two or more episodes of angina per week. Previous history of myocardial infarction, coronary artery bypass graft (CABG) surgery,percutaneous coronary intervention (PCI) or any combination of the above. Prescribed optimal medical therapy. Hypercholesterolaemia with an elevated Lp(a) > 50mg/dL and an LDL-cholesterol less than 4.0mmol/L despite optimal lipid lowering drug therapy. Exclusion Criteria: Patients with poor calibre veins for cannulation. Patients with any other chronic systemic illness such as liver or renal failure, neoplastic disease, overt cardiac failure, unstable coronary artery disease, coronary revascularisation or a myocardial infarction within the previous eight weeks. Pregnancy, untreated diabetes mellitus, untreated arterial hypertension, and those with general contraindications to undergoing Cardiovascular magnetic resonance imaging or contraindications to adenosine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: First Lipoprotein Apheresis, then sham apheresis<br>Three months of weekly lipoprotein apheresis, 1 month washout, then three month sham apheresis | Other: Lipoprotein Apheresis<br>* Weekly lipoprotein apheresis for 3 months<br>|
| Sham Comparator: First Sham Apheresis, then Lipoprotein Apheresis<br>Three months of weekly sham apheresis, 1 month washout, then three month lipoprotein Apheresis | Other: Sham Apheresis<br>* Weekly sham (placebo) apheresis for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging | Baseline compare to 3 month, changes presented Determine the impact of lipoprotein apheresis on quantitative myocardial perfusion measured by stress/rest cardiovascular magnetic resonance imaging. Increase means better outcome | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging | Changes from baseline to 3 months | 3 months | 
| Change in Endothelial Vascular Function | EndoPat LnRHI - natural logarithm of reactive hyperaemia index. Increase - better outcome | Within 7 days before and after 3 months of weekly lipoprotein apheresis | 
| Change in Seattle Angina Questionnaire Score | SAQ-Angina stability, increase means improvement. 0-100 scale, Higher score means improvements | 3 months | 
| Change in SF-36 Quality of Life Score | Quality of Life score following, 0-100 score, high score improve quality of life | 3 months | 
| Change in Exercise Capacity Determined by Six Minute Walk Test | Six minute walk test, patient can walk longer distance means improvements | 3 months | 
| Changes in Markers of Thrombogenesis | Thrombogenesis, Reduce value is better to the patients | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory Angina, Lipoprotein