Impact of PCSK9 Inhibitors on Coronary Microvascular Dysfunction in Patients With Atherosclerotic Cardiovascular Disease Proved by Myocardial Ischemia and Needing Coronarography (MICROPROTECT)

Grenoble Alpes University Hospital Center (CHU)

Status and phase

Unknown

Phase 2

Conditions

Atherosclerotic Cardiovascular Disease

Treatments

Drug: Evolocumab 140 MG/ML [Repatha]

Study type

Interventional

Funder types

Other

Identifiers

NCT04338165

38RC19.186

Details and patient eligibility

About

Proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (anti-PCSK9) significantly reduce the serum LDL-C level, leading to a regression of the coronary epicardial plaque demonstrated by intracoronary ultrasonography (IVUS), as well as cardiovascular events (CV) in patients with atherosclerotic CV disease treated with statin. The impact of PCSK9 inhibition on coronary microcirculation has never been assessed. However, microvascular coronary dysfunction (CMVD) is a powerful prognostic marker, irrespective of conventional CV risk factors, but also of the severity of the epicardial coronary involvement detected during coronary angiography. The investigators hypothesized that anti-PCSK9 would decrease CMVD, measured by the microcirculatory resistance index (MRI) during coronary angioplasty (Percutaneous coronary intervention, PCI) in patients with myocardial ischemia proved in myocardial scintigraphy.

Enrollment

66 estimated patients

Sex

All

Ages

40 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female patient, aged 40 to 85,
More than 50 kilograms
Defined at high cardiovascular risk according to European guidelines
LDL-C level ≥ 0.7 g / L (biological assessment of less than 6 months)
Having benefited from myocardial scintigraphy
For which coronarography is indicated according to European guidelines
Affiliated with social security,
Signed informed consent form

Exclusion criteria

Clinical presentation of unstable angina
Patient whose state of physical or psychological health could compromise the obtaining of his informed consent and his compliance with the requirements of the protocol, with the study evaluation, procedures or completion.
End stage disease (estimated survival of less than one year)
Severe renal dysfunction, defined as an estimated creatinine clearance (MDRD) < 30 mL/min at screening
Contra-indication to adenosin : hypersensitivity to active active substance or to any of the excipients, type II or III atrioventricular block or atrial disease (except for pacemaker users), long QT syndrome, severe arterial hypotension, acute heart failure, asthma and severe chronic obstructive pulmonary disease, unstable angina unstabilized by drug therapy, taking dipyridamole, aminophylline, theophylline or other xanthine base within 24 hours prior to adenosine administration
Contra-indication to heparin: hypersensitivity to active substance or to any of the excipients, past heparin induced thrombopenia type II, haemorrhage.
Prior Coronary Artery Bypass Graft Surgery (CABG)
Prior myocardial infarction in the territory of ischemia
New York Heart Association (NYHA) class III or IV, or last known left ventricular ejection fraction < 30%
Known hemorrhagic stroke at any time
Uncontrolled or recurrent ventricular tachycardia
Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 180 mmHg or diastolic BP (DBP) > 110 mmHg
Actual use of PCSK9 inhibitor (evolocumab or others)
Untreated or inadequately treated hyperthyroidism or hypothyroidism, controlled by biological assessment if needed, defined by thyroid stimulating hormone (TSH) < lower limit of normal (LLN) or > 1.5 times the upper limit of normal (ULN), respectively, and free thyroxine (T4) levels that are outside normal range at screening
Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN at screening
Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal)
Personal or family history of hereditary muscular disorders
LDL apheresis within 12 months prior to randomization
Creatinine Phosphokinase (CPK) > 5 ULN at screening
Active infection or others active disease judge by investigator incompatible with the protocol completion
Main known active infection including positive viral serology (Human Immunodeficiency Virus, Hepatitis B Virus and Hepatitis C Virus)
Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 10 years
Known sensitivity to evolocumab or their excipients to be administered during dosing or natural rubber / latex
Patient likely to not be available to complete all protocol-required study visits or procedures.
Patient in exclusion period of another study
Woman able to procreate in the absence of highly effective contraception
Persons referred to in Articles L1121-6 to L1121-8 of the French code of public health (this corresponds to all persons protected: pregnant or parturient women, breastfeeding mothers, persons deprived of liberty by judicial or administrative decision, persons subject to a legal protection measure).