Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis- CloPidogREl for Primary preVENTION (HOST-PREVENTION)

Coronary Artery Disease Clinical Trial

Official title:

Efficacy and Safety of Clopidogrel for Primary Prevention in Patients With Subclinical Coronary Atherosclerosis Identified on Imaging

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05845489
• Other study ID #: H-2212-044-1385
• Status: Recruiting
• Phase: Phase 4
• Start date: March 9, 2023
• Est. completion date: March 31, 2030

Study information

• Verified date: May 2023
• Source: Seoul National University Hospital
• Contact: Jung-Kyu Han, MD, PhD
• Phone: 821026765736
• Email: hpcrates[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will evaluate the efficacy and safety of clopidogrel for primary prevention in patients diagnosed with coronary atherosclerosis on imaging that did not require revascularization therapy.

The trial will test the hypothesis that clopidogrel is beneficial in preventing major adverse cardiovascular and cerebrovascular events (MACCE) in patients with subclinical coronary atherosclerosis identified on imaging.

Description:

Coronary artery disease (CAD) is the most prevalent and lethal disease worldwide. Even though various studies have been performed regarding the prevention or treatment of CAD and its related cardiovascular events, the prevalence of CAD and the incidence of cardiovascular events are increasing.

Antiplatelet agents are among the most widely used drugs for preventing cardiovascular events. The efficacy of antiplatelet agents has been extensively proven in secondary prevention for cardiovascular events in CAD patients, and their use has been recommended in current guidelines. However, there is still controversy surrounding the prescription of antiplatelet agents for the primary prevention of cardiovascular events in CAD patients due to their unknown clear efficacy and risk of bleeding complications.

Recent studies reported the limited efficacy of aspirin in old patients, diabetes patients, or patients with cardiovascular events risks. However, the efficacy or safety of antiplatelet therapy in patients with subclinical coronary atherosclerosis has not been thoroughly investigated. These patients are at higher risk of cardiac death or myocardial infarction compared to patients without coronary atherosclerosis.

In this regard, the investigators will evaluate the efficacy and safety of clopidogrel for primary prevention in patients diagnosed with coronary atherosclerosis on imaging that did not require revascularization therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9930
• Est. completion date: March 31, 2030
• Est. primary completion date: March 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Male or female aged =40 years

• Patients with subclinical coronary atherosclerosis identified from coronary CT angiography or coronary angiography within 2 years without clinical events after an imaging study

• Without significant coronary artery stenosis (Diameter stenosis >50%), which needs revascularization

• Agreement to give written informed consent

Exclusion Criteria:

• A history of a diagnosed cardiovascular or cerebrovascular disease (myocardial infarction, heart failure, peripheral artery disease, stroke, transient ischemic attack, carotid artery stenosis>50%, carotid artery intervention)

• A history of coronary artery intervention or coronary artery bypass graft surgery, which needs chronic maintenance of antiplatelet therapy

• Absolute contraindication or allergy to clopidogrel

• Patients receiving anticoagulants for other comorbidities

• A history of Bleeding diathesis, known coagulopathy, or major bleeding, BARC class =3, resulting in the stop of antiplatelet agents

• Planned surgery or intervention which needs to stop antiplatelet agents =1 month

• Presence of non-cardiac comorbidity with life expectancy = 5 years at randomization

• Females with pregnancy or breast-feeding

• Patients who are thought to be inappropriate for the trial based on physicians' decision

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Clopidogrel treatment group
Patients assigned to the clopidogrel treatment group will maintain clopidogrel 75mg once a day for at least 5 years.

Other:
• No antiplatelet or anticoagulant group
Patients assigned to the no antiplatelet or anticoagulant group will not prescribe antithrombotics for at least 5 years. However, when there is a medical need for antithrombotic therapy during the follow-up, the prescription of antithrombotics is permitted with reporting to the research board.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul	Other

Sponsors (7)

Lead Sponsor	Collaborator
Seoul National University Hospital	Hallym University Kangnam Sacred Heart Hospital, Hallym University Medical Center, Hanyang University, Kangbuk Samsung Hospital, Keimyung University Dongsan Medical Center, Wonju Severance Christian Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (14)

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Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Munoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. doi: 10.1161/CIR.0000000000000678. Epub 2019 Mar 17. No abstract available. Erratum In: Circulation. 2019 Sep 10;140(11):e649-e650. Circulation. 2020 Jan 28;141(4):e60. Circulation. 2020 Apr 21;141(16):e774. — View Citation

ASCEND Study Collaborative Group; Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018 Oct 18;379(16):1529-1539. doi: 10.1056/NEJMoa1804988. Epub 2018 Aug 26. — View Citation

de Azevedo CF, Hadlich MS, Bezerra SG, Petriz JL, Alves RR, de Souza O, Rati M, Albuquerque DC, Moll J. Prognostic value of CT angiography in patients with inconclusive functional stress tests. JACC Cardiovasc Imaging. 2011 Jul;4(7):740-51. doi: 10.1016/j.jcmg.2011.02.017. — View Citation

Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, Howard G, Pearson TA, Rothwell PM, Ruilope LM, Tendera M, Tognoni G; ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018 Sep 22;392(10152):1036-1046. doi: 10.1016/S0140-6736(18)31924-X. Epub 2018 Aug 26. — View Citation

Habib PJ, Green J, Butterfield RC, Kuntz GM, Murthy R, Kraemer DF, Percy RF, Miller AB, Strom JA. Association of cardiac events with coronary artery disease detected by 64-slice or greater coronary CT angiography: a systematic review and meta-analysis. Int J Cardiol. 2013 Oct 30;169(2):112-20. doi: 10.1016/j.ijcard.2013.08.096. Epub 2013 Sep 7. — View Citation

Hennekens CH, Dyken ML, Fuster V. Aspirin as a therapeutic agent in cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1997 Oct 21;96(8):2751-3. doi: 10.1161/01.cir.96.8.2751. No abstract available. — View Citation

Ittaman SV, VanWormer JJ, Rezkalla SH. The role of aspirin in the prevention of cardiovascular disease. Clin Med Res. 2014 Dec;12(3-4):147-54. doi: 10.3121/cmr.2013.1197. Epub 2014 Feb 26. — View Citation

Koo BK, Kang J, Park KW, Rhee TM, Yang HM, Won KB, Rha SW, Bae JW, Lee NH, Hur SH, Yoon J, Park TH, Kim BS, Lim SW, Cho YH, Jeon DW, Kim SH, Han JK, Shin ES, Kim HS; HOST-EXAM investigators. Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet. 2021 Jun 26;397(10293):2487-2496. doi: 10.1016/S0140-6736(21)01063-1. Epub 2021 May 16. — View Citation

McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, Reid CM, Lockery JE, Kirpach B, Storey E, Shah RC, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Johnston CI, Ryan J, Radziszewska B, Jelinek M, Malik M, Eaton CB, Brauer D, Cloud G, Wood EM, Mahady SE, Satterfield S, Grimm R, Murray AM; ASPREE Investigator Group. Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. N Engl J Med. 2018 Oct 18;379(16):1509-1518. doi: 10.1056/NEJMoa1805819. Epub 2018 Sep 16. — View Citation

Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurheartj/ehy394. No abstract available. Erratum In: Eur Heart J. 2019 Oct 1;40(37):3096. — View Citation

Schlett CL, Banerji D, Siegel E, Bamberg F, Lehman SJ, Ferencik M, Brady TJ, Nagurney JT, Hoffmann U, Truong QA. Prognostic value of CT angiography for major adverse cardiac events in patients with acute chest pain from the emergency department: 2-year outcomes of the ROMICAT trial. JACC Cardiovasc Imaging. 2011 May;4(5):481-91. doi: 10.1016/j.jcmg.2010.12.008. — View Citation

Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Back M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Di Angelantonio E, Franco OH, Halvorsen S, Hobbs FDR, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. doi: 10.1093/eurheartj/ehab484. No abstract available. Erratum In: Eur Heart J. 2022 Nov 7;43(42):4468. — View Citation

Yazdanyar A, Newman AB. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin Geriatr Med. 2009 Nov;25(4):563-77, vii. doi: 10.1016/j.cger.2009.07.007. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major adverse cardiovascular and cerebrovascular events (MACCE)	A composite of all-cause death, non-fatal myocardial infarction, any coronary revascularization, ischemic stroke, or transient ischemic attack	5 years after randomization
Secondary	Major adverse cardiovascular and cerebrovascular events (MACCE) in men	A composite of all-cause death, non-fatal myocardial infarction, any coronary revascularization, ischemic stroke, or transient ischemic attack	5 years after randomization
Secondary	Major adverse cardiovascular and cerebrovascular events (MACCE) in women	A composite of all-cause death, non-fatal myocardial infarction, any coronary revascularization, ischemic stroke, or transient ischemic attack	5 years after randomization
Secondary	Net adverse clinical event	A composite of all-cause death, non-fatal myocardial infarction, any coronary revascularization, ischemic stroke or transient ischemic attack, major bleeding	5 years after randomization
Secondary	All-cause death		5 years after randomization
Secondary	Non-fatal myocardial infarction		5 years after randomization
Secondary	Any coronary revascularization		5 years after randomization
Secondary	Ischemic stroke or Transient ischemic attack		5 years after randomization
Secondary	Any non-coronary revascularization		5 years after randomization
Secondary	Major bleeding events	BARC classification, type 3 or 5	5 years after randomization
Secondary	BARC type 2 bleeding events		5 years after randomization
Secondary	BARC type 3 bleeding events		5 years after randomization
Secondary	BARC type 5 bleeding events		5 years after randomization