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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Evolocumab, 420 milligrams | Experimental | Single injection of 420 milligrams of evolocumab (REPATHA®) one month before coronary angiography and coronary microcirculation (IMR) measurement. |
|
| Control arm | No Intervention | Measurement of coronary microcirculation (IMR) during coronary angiography, without prior evolocumab injection. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Evolocumab 140 MG/ML [Repatha] | Drug | 3 injections of evolocumab 140 milligrams performed within 30 minutes and self-administered (subcutaneously in the abdomen, thigh, or upper arm) |
| Measure | Description | Time Frame |
|---|---|---|
| Impact of a PCSK9 inhibitor treatment on coronary microvascular dysfunction (CMVD) at 4 weeks in patients with atherosclerotic cardiovascular disease. | Index of microcirculatory resistance (IMR), measured during invasive coronary angiography and expressed in mmHg.s | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Impact of a PCSK9 inhibitor treatment on soluble VE-cadherin rate (sVE). | Measurement of sVE rate at baseline and four weeks after treatment with evolocumab or without treatment. | 4 weeks |
| Impact of a PCSK9 inhibitor treatment on brachial hyperemia (HB). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gilles Barone-Rochette, MD, PhD | Contact | +33476765172 | gbarone@chu-grenoble.fr | |
| Clémence Charlon | Contact | ccharlon@chu-grenoble.fr |
| Name | Affiliation | Role |
|---|---|---|
| Gilles Barone-Rochette, MD, PhD | CHU Grenoble Alpes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Grenoble University Hospital | Recruiting | Grenoble | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27222591 | Background | Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FDR, Lochen ML, Lollgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WMM, Binno S; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-2381. doi: 10.1093/eurheartj/ehw106. Epub 2016 May 23. No abstract available. | |
| 28304224 |
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Variation of the luminal diameter of the humeral artery with baseline and four weeks after treatment with evolocumab or without treatment. |
| 4 weeks |
| Impact of a PCSK9 inhibitor treatment on the rate of peri-procedural myocardial infarction. | Troponin I level after PCI (peri-procedural myocardial pain will be defined as a post-angioplasty troponin level 10 times higher than the 99th percentile of troponin I). | 4 weeks |
| Correlations between invasive and non-invasive (myocardial scintigraphy - myocardial perfusion entropy (MPE), concentration of sVE, HB) measurements of coronary microvascular dysfunction. | IMR, MPE, sVE and the variation of the luminal diameter of the humeral artery. | 4 weeks |
| Correlations between the cardiovascular risk and the concentration of sVE and MPE. | Risk score, sVE rate and MPE. | 4 weeks |
| Background |
| Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17. |
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| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C577155 | evolocumab |
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