Coronary artery disease MedDRA version: 20.0 Level: PT Classification code 10005422 Term: Blood cholesterol System Organ Class: 10022891 - Investigations MedDRA version: 20.0 Level: LLT Classification code 10002434 Term: Angiogram coronary System Organ Class: 10022891 - Investigations
Conditions
Interventions
Trade Name: Repatha
Product Name: Repatha
Pharmaceutical Form:
Pharmaceutical form of the placebo: Injection
Route of administration of
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients aged between 18 and 80 years, with a clinical indication for coronary angiography and: 1. Willing to provide consent: Provide written (signed and dated) informed consent and be capable of understanding the study and co-operating with treatment and follow-up. 2. Raised levels of fasting (>9h) LDL-cholesterol (=2mmol/L) either on optimal statin therapy (90% of overall sample) or intolerants to statins (restricted to 10% of overall sample) and 3. At least one other risk factor for vascular disease or established vascular disease. Optimal statin therapy will be defined as at least 4 weeks of atorvastatin 40mg or more, with no change in statin dose during this period. Definition of vascular risk factors 1. Diabetes (type I or type II), formally diagnosed, on therapy; 2. Current cigarette smoking; 3. Diagnosis of hypertension, on treatment; 4. Early family history of established vascular disease (brother or father with vascular disease before 55yo or sister or mother with vascular disease before 65yo); 5. Most recent LDL-C = 3.4 mmol/L despite at least 40mg of atorvastatin. Definition of established vascular disease 1. Previously documented coronary disease, stable or unstable. 1.1 History of acute coronary syndrome; 1.2 Previous coronary revascularisation; 1.3 Clinical syndrome of stable angina; 1.4 Previous documented at least one moderate coronary stenosis on coronary angiography. 2. Previously formally diagnosed symptomatic peripheral vascular disease; 3. Previously documented cerebrovascular ischaemic event; Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Patients unable or unwilling to provide written informed consent; 2. Patients unable to undergo cardiac catheterisation; 3. Patients with severe asthma (contraindication to adenosine); 4. Uncontrolled hypertension (systolic BP >180mmHg or DBP >110mmHg, despite ongoing therapy); 5. Clinical heart failure NYHA class III/IV or Ejection Fraction on imaging modality (Echo, MRI) 95% diameter) epicardial coronary stenosis; 8. Recent (last 12 months) clinically significant cerebrovascular event (including ischaemic or haemorrhagic events); 9. End-stage renal failure (eGFR 3x ULN 11. Current use of PCSK9 inhibitor; 12. Malignancy with life expectancy 40 IU/L (or according to the definition of "postmenopausal range" for the laboratory involved) in a female < 55 years old unless the subject has undergone bilateral oophorectomy. 15.2. Acceptable methods of preventing pregnancy include not having intercourse, birth control pills, injections, implants, or patches, intrauterine devices (IUDs), tubal ligation/occlusion, sexual activity with a male partner who has had a vasectomy, condom or occlusive cap (diaphragm or cervical/vault caps) used with Spermicide 16. Subject is pregnant or breast feeding, or planning to become pregnant or to breastfeed during treatment with IP and/ or within 15 weeks after the end of treatment with IP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Our secondary research question will be: By what mechanism does treatment with PCSK9 inhibitors affect flow of blood in these arteries?;Primary end point(s): The primary endpoint of the study will be maximal coronary flow velocity (in cm/s) measured invasively, 12 weeks after Evolocumab therapy. It is hypothesized that Evolocumab will augment maximal coronary flow by at least 10%.;Main Objective: This study aims to show the effect of strong anti-cholesterol medicines called PCSK9 inhibitors on the flow of blood inside the coronary arteries that supply blood to heart muscle. Our main research question will be: Does treatment with PCSK9 inhibitors improves the flow of blood in coronary arteries and in the smaller blood vessels that they supply?;Timepoint(s) of evaluation of this end point: Coronary flow velocity will be measured at baseline and after three months of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Coronary Flow Reserve (CFR), measured invasively, 12 weeks after evolocumab therapy; It is hypothesized that Evolocumab will augment CFR. 2. Hyperaemic Microvascular Resistance (HMR, in mmHg/cm/s), measured invasively, 12 weeks after Evolocumab therapy. It is hypothesized that Evolocumab will reduce HMR. 3. Adenosine-mediated maximal coronary flow velocity (in cm/s) and coronary flow reserve, measured non-invasively, 12 weeks after Evolocumab therapy; It is hypothesized that Evolocumab will augment coronary flow when measured non-invasively. Exploratory endpoints 4. Quantification of the effect of Evolocumab on Coronary Waves (using Wave Intensity Analysis, derived from invasive pressure and flow data)15. It is plausible to speculate that Evolocumab therapy will increase coronary suction. 5. Adenosine-mediated maximal coronary flow velocity (in cm/s) and coronary flow reserve, measured non-invasively, 6 months after Evolocumab therapy. It is plausible to speculate that Evolocumab therapy will increase coronary flow further (when compared to baseline and 12 weeks follow up). 6. Exercise-induced maximal coronary flow velocity (in cm/s) and coronary flow reserve, measured non-invasively, 12 weeks and 6 months after Evolocumab therapy; It is plausible to speculate that Evolocumab therapy will increase exercise-induced maximal coronary flow. ;Timepoint(s) of evaluation of this end point: These measures will be recorded at baseline, after 3 months of therapy and non-invasive measures will be recorded again after a further 3 months of therapy in the treatment arm only. | — |
Countries
United Kingdom
Contacts
Public ContactRuth Nicholson
AHSC Joint Research Office, Imperial College NHS Trust
Outcome results
None listed