Clinical trial NCT01796912: Lipoprotein Apheresis in Refractory Angina Study
Official title: Clinical Outcomes, Perfusion and Vascular Function in Patients With Refractory Angina and Raised Lipoprotein (a), Treated With Lipoprotein Apheresis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Refractory Angina
Raised Lipoprotein(a)>50mg/dL or >500mg/L
Keywords: Refractory Angina
Lipoprotein
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2013-02-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in Quantitative Myocardial Perfusion Measured by Stress/Rest Cardiovascular Magnetic Resonance Imaging
timeFrame: 3 months
Secondary outcomes:
measure: Change in Carotid Atherosclerosis/Plaque Burden Determined by Cardiovascular Magnetic Resonance Imaging
timeFrame: 3 months
measure: Change in Endothelial Vascular Function
timeFrame: Within 7 days before and after 3 months of weekly lipoprotein apheresis
measure: Change in Seattle Angina Questionnaire Score
timeFrame: 3 months
measure: Change in SF-36 Quality of Life Score
timeFrame: 3 months
measure: Change in Exercise Capacity Determined by Six Minute Walk Test
timeFrame: 3 months
measure: Changes in Markers of Thrombogenesis
timeFrame: 3 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton and Harefield NHS Foundation Trust
Study officials:
affiliation: Imperial College London
name: Dudley Pennell, MB BChir MA MD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Brompton and Harfield Hospital, Imperial College
name: Mahmoud Barbir, MB BCh, FRCP
role: STUDY_DIRECTOR
References:
citation: Khan TZ, Hsu LY, Arai AE, Rhodes S, Pottle A, Wage R, Banya W, Gatehouse PD, Giri S, Collins P, Pennell DJ, Barbir M. Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial. Eur Heart J. 2017 May 21;38(20):1561-1569. doi: 10.1093/eurheartj/ehx178.