LaRCA: Specific Lp(a) Apheresis for Regression of Coronary and Carotid Atherosclerosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Specific Lp(a) apheresis & Atorvastatin Specific Lp(a) apheresis was performed with "Lp(a) Lipopak" immunosorbent columns ("POCARD" Ltd., Moscow, Russia) with sheep polyclonal monospecific antibodies against human Lp(a)/apo(a) weekly during 18 months. On the background - standard medical therapy in accordance with the recommendations for secondary prevention of CHD. |
Procedure: Specific 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
Other Names:
|
| No Intervention: Atorvastatin Standard medical therapy in accordance with the recommendations for secondary prevention of CHD |
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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 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
- 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
Other Outcome Measures
- 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
- 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 hemoglobin level [From Baseline to Week 4, 36, 72]
- 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]
Eligibility Criteria
Criteria
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
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chronic infectious and inflammatory diseases
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familial hypercholesterolemia
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TG ≥4.5 mmol/L (400 mg/dL)
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Active liver disease (ALT or AST >3 upper limit of normal (ULN), or total bilirubin
1.5 ULN);
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CK ≥3 ULN;
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Thyroid dysfunction;
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Renal dysfunction (creatinine clearance (Cockcroft-Gault Equation) ≤30 ml/min);
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Uncontrolled diabetes (HbA1c ≥7.0%);
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Coagulopathies;
-
Lipid-lowering drugs, except statins for the last month
-
Known statin or immunoadsorption intolerance
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Russian Cardiology Research and Production Center | Moscow | Russian Federation | 121552 |
Sponsors and Collaborators
- Russian Cardiology Research and Production Center
- Clinical Diagnostic Center MEDSI
- Moscow State Government
Investigators
- Principal Investigator: Sergei Pokrovsky, PhD, DSc, Russian Cardiology Research and Production Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 01200953720