RECRUITINGOBSERVATIONAL

Assessment of Lipoprotein(a) and Endogenous Fibrinolysis in Atherosclerotic Cardiovascular Disease/Aortic Valve Disease

About This Trial

Prior studies have shown that impaired endogenous fibrinolysis is a novel, independent cardiovascular risk factor in patients with myocardial infarction and there is currently no known chronic treatment to enhance endogenous fibrinolysis. To date, no therapies have been able to sufficiently reduce Lp(a) and therefore it was considered to be a non-modifiable cardiovascular risk factor. New data, however, has shown that PCSK9 inhibitors and inclisiran (medication that you have been deemed eligible for in order to help further reduce your cholesterol levels) to reduce Lp(a) levels by approximately 20-25%. The aim of this study to is to assess: 1. if there is an association between raised Lp(a) level in blood and the effectiveness of endogenous fibrinolysis (lysis time). 2. whether lowering Lp(a) with PCSK9i or inclisiran can enhance endogenous fibrinolysis

Who May Be Eligible (Plain English)

Who May Qualify: 1\) Male and female patients aged 18 years or over 2\) i) Patients identified as eligible for treatment with either a PCSK9i or inclisiran ii) Patients diagnosed with moderate or severe calcific aortic stenosis based on non-enhanced Cardiac CT scan 3\) Willing and able to understand the Participant Information Sheet and provide willing to sign a consent form 4\) The patient must agree to comply with the drawing of blood samples for the assessments 5\) The patient does not meet any of the exclusion criteria Who Should NOT Join This Trial: 1. Inability to provide valid willing to sign a consent form 2. Male and female patients aged \< 18 years of age 3. The patient has, in the opinion of the investigator, significant neurological, hepatic, renal, endocrine, gastrointestinal, pulmonary, haemorrhagic, metabolic or other disease likely to confound the study requirements or analyses 4. The patient has a history of substance abuse or demonstrates signs or clinical features of active substance abuse or psychiatric disease 5. Alcohol consumption above recommended safe levels (i.e., more than 14 units per week) due to the potential effects of high alcohol levels on platelet reactivity 6. Any illness deemed significant by the investigator during the four (4) weeks preceding the screening period of the study 7. Any major bleeding diathesis or blood dyscrasia (platelets \< 70 x 109/l, Hb \< 8 g/dl, INR \> 1.4, APTT \> x 2 upper normal limit, leucocyte count \< 3.5 x 109/l, neutrophil count \< 1 x 109/l) 8. Currently enrolled in an investigational device or non-licensed drug trial Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1\) Male and female patients aged 18 years or over 2\) i) Patients identified as eligible for treatment with either a PCSK9i or inclisiran ii) Patients diagnosed with moderate or severe calcific aortic stenosis based on non-enhanced Cardiac CT scan 3\) Willing and able to understand the Participant Information Sheet and provide informed consent 4\) The patient must agree to comply with the drawing of blood samples for the assessments 5\) The patient does not meet any of the exclusion criteria Exclusion Criteria: 1. Inability to provide valid informed consent 2. Male and female patients aged \< 18 years of age 3. The patient has, in the opinion of the investigator, significant neurological, hepatic, renal, endocrine, gastrointestinal, pulmonary, haemorrhagic, metabolic or other disease likely to confound the study requirements or analyses 4. The patient has a history of substance abuse or demonstrates signs or clinical features of active substance abuse or psychiatric disease 5. Alcohol consumption above recommended safe levels (i.e., more than 14 units per week) due to the potential effects of high alcohol levels on platelet reactivity 6. Any illness deemed significant by the investigator during the four (4) weeks preceding the screening period of the study 7. Any major bleeding diathesis or blood dyscrasia (platelets \< 70 x 109/l, Hb \< 8 g/dl, INR \> 1.4, APTT \> x 2 upper normal limit, leucocyte count \< 3.5 x 109/l, neutrophil count \< 1 x 109/l) 8. Currently enrolled in an investigational device or non-licensed drug trial

Treatments Being Tested

DIAGNOSTIC_TEST

Thrombotic assessment

The Global Thrombosis Test (Thromboquest Limited, UK) is an in vitro method imitating high shear stress conditions akin to that which exist in a severely stenosed artery. The test measures platelet reactivity (occlusion time) and endogenous fibrinolysis time (lysis time). Thromboelastography is a technique that assesses the whole process of clotting and its viscoelastic properties, from the initial activation and aggregation of platelets, to the role of thrombin and finally the stability of the formed clot, as a measure of fibrinolytic resistance. Plasma will be stored for subsequent analysis of other thrombotic, fibrinolytic, inflammatory and coagulation markers as deemed appropriate. For patients deemed eligible for treatment with either a PCSK9i or inclisiran, this will be assessed prior to commencing treatment and also 3-6 months after starting treatment. This will only be assessed once for patients with moderate or severe aortic valve calcification.

DIAGNOSTIC_TEST

Measurement of Lp(a)

Lp(a) will be measured by particle enhanced immunotubidimetricassay. Human lipoprotein (a) agglutinates with latex particles coated with anti-Lp(a) antibodies. The precipitate is determined turbidimetrically at 800 / 660 nm. The platform employed will be the Roche® Immunoassay Analyser (Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim). Traceability: This method has been standardized against the IFCC (International Federation of Clinical Chemistry) reference material SRM2B for nmol/L. For patients deemed eligible for treatment with either a PCSK9i or inclisiran, this will be assessed prior to commencing treatment and also 3-6 months after starting treatment. This will only be assessed once for patients with moderate or severe aortic valve calcification.

Locations (1)

East and North Herts NHS Trust

Stevenage, United Kingdom