Raised Lipoprotein(a)>50mg/dL or >500mg/L, Refractory Angina
Conditions
Keywords
Refractory Angina, Lipoprotein
Brief summary
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
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.
Interventions
OTHERLipoprotein Apheresis
Weekly lipoprotein apheresis for 3 months
OTHERSham Apheresis
Weekly sham (placebo) apheresis for 3 months
Sponsors
National Institute for Health Research, United Kingdom
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging | 3 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endothelial Vascular Function | Within 7 days before and after 3 months of weekly lipoprotein apheresis | EndoPat LnRHI - natural logarithm of reactive hyperaemia index. Increase - better outcome |
| Change in Seattle Angina Questionnaire Score | 3 months | SAQ-Angina stability, increase means improvement. 0-100 scale, Higher score means improvements |
| Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging | 3 months | Changes from baseline to 3 months |
| Change in Exercise Capacity Determined by Six Minute Walk Test | 3 months | Six minute walk test, patient can walk longer distance means improvements |
| Changes in Markers of Thrombogenesis | 3 months | Thrombogenesis, Reduce value is better to the patients |
| Change in SF-36 Quality of Life Score | 3 months | Quality of Life score following, 0-100 score, high score improve quality of life |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participant Participant were 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 then crossovered to the opposite study arm with the protocol repeated. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | All Study Participant | — |
|---|---|---|
| Age, Continuous | 60.9 years STANDARD_DEVIATION 9.5 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United Kingdom | 20 Participants | — |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 19 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
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
Time frame: 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lipoprotein Apheresis | Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging | 0.47 ratio |
| Sham Apheresis | Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging | -0.16 ratio |
p-value: 0.001t-test, 2 sided
Secondary
Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging
Changes from baseline to 3 months
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lipoprotein Apheresis | Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging | -335 mm3 |
| Sham Apheresis | Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging | 127 mm3 |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
Change in Endothelial Vascular Function
EndoPat LnRHI - natural logarithm of reactive hyperaemia index. Increase - better outcome
Time frame: Within 7 days before and after 3 months of weekly lipoprotein apheresis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lipoprotein Apheresis | Change in Endothelial Vascular Function | -0.05 index |
| Sham Apheresis | Change in Endothelial Vascular Function | -0.03 index |
p-value: 0.14t-test, 2 sided
Secondary
Change in Exercise Capacity Determined by Six Minute Walk Test
Six minute walk test, patient can walk longer distance means improvements
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lipoprotein Apheresis | Change in Exercise Capacity Determined by Six Minute Walk Test | 70.5 meter |
| Sham Apheresis | Change in Exercise Capacity Determined by Six Minute Walk Test | 3.5 meter |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
Change in Seattle Angina Questionnaire Score
SAQ-Angina stability, increase means improvement. 0-100 scale, Higher score means improvements
Time frame: 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lipoprotein Apheresis | Change in Seattle Angina Questionnaire Score | 17.5 units on a scale |
| Sham Apheresis | Change in Seattle Angina Questionnaire Score | -1.75 units on a scale |
p-value: 0.016t-test, 2 sided
Secondary
Change in SF-36 Quality of Life Score
Quality of Life score following, 0-100 score, high score improve quality of life
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lipoprotein Apheresis | Change in SF-36 Quality of Life Score | 7.5 units on a scale |
| Sham Apheresis | Change in SF-36 Quality of Life Score | -2 units on a scale |
p-value: 0.001Wilcoxon (Mann-Whitney)
Secondary
Changes in Markers of Thrombogenesis
Thrombogenesis, Reduce value is better to the patients
Time frame: 3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lipoprotein Apheresis | Changes in Markers of Thrombogenesis | -355 seconds |
| Sham Apheresis | Changes in Markers of Thrombogenesis | 36 seconds |
p-value: 0.005Wilcoxon (Mann-Whitney)