Atherosclerosis, Carotid Artery Diseases, Coronary Disease
Conditions
Keywords
Lipoprotein(a);, Lp(a) immunoadsorption;, Apheresis;, Coronary atherosclerosis;, Carotid Atherosclerosis;, Intima-media thickness;, Regression;, Quantitative Coronary Angiography;, Intravascular Ultrasound;, Virtual Histology;, Plaque;, Atorvastatin;
Brief summary
To evaluate whether specific lipoprotein(a) apheresis on the top of optimal medical therapy could affect atherosclerotic disease burden in coronary and carotid arteries of coronary heart disease patients with elevated Lp(a) levels.
Detailed description
Following the hypothesis that if Lp(a) excess has a pathogenic role in atherogenesis, then specific elimination of circulating Lp(a) should affect plaque growth and stability, we evaluated the efficacy of Lp(a) apheresis on changes in coronary plaque volume and composition and carotid intima-media thickness in patients with CHD on the background of optimal medical treatment.
Interventions
PROCEDURESpecific Lp(a) apheresis
Specific Lp(a) apheresis procedures were carried out weekly with Lp(a) Lipopak columns (POCARD Ltd., Moscow, Russia) according to the standard protocol
Sponsors
Clinical Diagnostic Center MEDSI
Moscow State Government
Russian Cardiology Research and Production Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Stable coronary heart disease (CHD) requiring a clinically indicated coronary angiography. * Lp(a) ≥50 mg/dL * LDL-C \<2.6 mmol/L (100 mg/dL) * Signed written informed consent form to participate in the study
Exclusion criteria
* history of acute coronary syndrome or surgical intervention within prior 3 months to inclusion * chronic infectious and inflammatory diseases * familial hypercholesterolemia * TG ≥4.5 mmol/L (400 mg/dL) * Active liver disease (ALT or AST \>3 upper limit of normal (ULN), or total bilirubin \>1.5 ULN); * CK ≥3 ULN; * Thyroid dysfunction; * Renal dysfunction (creatinine clearance (Cockcroft-Gault Equation) ≤30 ml/min); * Uncontrolled diabetes (HbA1c ≥7.0%); * Coagulopathies; * Lipid-lowering drugs, except statins for the last month * Known statin or immunoadsorption intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Diameter Stenosis | From Baseline to End of Study (Week 72) | The absolute change from baseline to 18 months in mean percent diameter stenosis, determined by quantitative coronary angiography (QCA) as the narrowest lesion in each segment and calculated as: ((reference diameter-minimal lumen diameter (MLD))/reference diameter)x100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Numbers of Coronary segments Showing Regression | From baseline to End of study (Week 72) | Clinically relevant regression or progression was defined as a change from baseline to follow up of ≥10% for percent diameter stenosis |
| Number of Carotid Segments showing Regression | From Baseline to End of study (Week 72) | Carotid IMT progression criterion for the 18 months of treatment was considered as growth rate of 0.02 mm (0.015 mm/yr). No changes or reduction in carotid IMT ≥ 0,02 mm served as criterion of stabilization and regression of carotid atherosclerosis, respectively. |
| Change in total atheroma volume (TAV) from baseline to 18 months post-therapy | From Baseline to Week 72 | TAV at baseline - TAV at Week 72 assessed by intravascular ultrasound (IVUS) imaging of a targeted coronary artery |
| Change in absolute volumes of plaque components | From Baseline to Week 72 | Mean change in absolute volumes of plaque components: fibrotic, fibrofatty, necrotic core or dense calcium, assessed by radiofrequency intravascular ultrasonographic (IVUS) imaging at baseline and 18 months post-therapy |
| Change in mean carotid intima-media thickness (IMT) | From Baseline to Week 36 (9 months) and to Week 72 (18 months) | Change from baseline in mean carotid IMT, as measured by duplex ultrasonography of common carotid arteries after 9 and 18 months. |
| Numbers of Coronary Plaques Showing Regression | From baseline to End of study (Week 72) | Regression was defined as decrease in TAV for all anatomically comparable cross sectional areas of targeted coronary artery from baseline of ≥ 0,1 mm cubed |
| Acute change in Lp(a) level | Once a week over 72 week period of active treatment | Difference in Lp(a) concentration before and after specific Lp(a) apheresis procedure calculated as the mean of all measurements |
| Change in quality of life (QOL) | from baseline to week 72 | To evaluate the impact of the specific Lp(a) removal therapy on the quality of life using Seattle Angina Questionnaire (SAQ) and Exercise stress test as compared with standard guideline-driven medical therapy of CHD patients |
| Change in relative amount of plaque components | From baseline to Week 72 | Mean change in relative amounts of plaque components: fibrotic, fibrofatty, necrotic core or dense calcium, assessed by radiofrequency intravascular ultrasonographic (IVUS) imaging at baseline and 18 months post-therapy |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in hemoglobin level | From Baseline to Week 4, 36, 72 | — |
| Change in high-density lipoprotein cholesterol (HDL-C) serum level | From Baseline to Week 4, 36, 72 | Mean changes in HDL-C level over the 18-month study period |
| Change in creatinine level | From Baseline to Week 4, 36, 72 | — |
| Change in creatine kinase (CK) level | From Baseline to Week 4, 36, 72 | — |
| Change in alanine transaminase (ALT) level | From Baseline to Week 4, 36, 72 | — |
| Change in aspartate transaminase (AST) level | From Baseline to Week 4, 36, 72 | — |
| Total Cholesterol (TC) Serum Level | From Baseline to Week 4, 36, 72 | Mean changes in TC level over the 18-month study period |
| Lipoprotein(a) (Lp(a)) serum levels | From Baseline to Week 4, 36, 72 | Mean changes in Lp(a) level over the 18-month study period |
| Low-density lipoprotein cholesterol (LDL-C) serum Level | From Baseline to Week 4, 36, 72 | Mean changes in LDL-C level over the 18-month study period |
| Change in corrected LDL-C (LDL-C corr) Serum level | From Baseline to Week 4, 36, 72 | Since all included patients had high Lp(a) levels, to avoid overestimation of LDL-C fraction estimated LDL-C levels were corrected for cholesterol derived from Lp(a). Corrected LDL-C (LDL-C corr) was calculated using Dahlen's modification of the Friedewald formula: LDL-C corr = TC - (HDL-C) - (TG / 2.2) - (0.3 x Lp(a) / 38.7). For values in mmol/L, Lp(a) in mg/dL |
| Change in triglycerides (TG) serum Level | From Baseline to Week 4, 36, 72 | Mean changes in TG level over the 18-month study period |
Countries
Russia
Outcome results
None listed