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

Official title

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

Overview

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.

Detailed 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.

Interventions

• 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.

Primary outcome measures

• Major adverse cardiovascular and cerebrovascular events (MACCE) [Time frame: at 2 years after the last enrollment]

Secondary outcome measures (11)

• Major adverse cardiovascular and cerebrovascular events (MACCE) [Time frame: at 5 years after the last enrollment]
• Net adverse clinical event [Time frame: at 2 years and 5 years after the last enrollment]
• All-cause death [Time frame: at 2 years and 5 years after the last enrollment]
• Non-fatal myocardial infarction [Time frame: at 2 years and 5 years after the last enrollment]
• Any coronary revascularization [Time frame: at 2 years and 5 years after the last enrollment]
• Ischemic stroke or Transient ischemic attack [Time frame: at 2 years and 5 years after the last enrollment]
• Any non-coronary revascularization [Time frame: at 2 years and 5 years after the last enrollment]
• Major bleeding events [Time frame: at 2 years and 5 years after the last enrollment]
• BARC type 2 bleeding events [Time frame: at 2 years and 5 years after the last enrollment]
• BARC type 3 bleeding events [Time frame: at 2 years and 5 years after the last enrollment]
• BARC type 5 bleeding events [Time frame: at 2 years and 5 years after the last enrollment]

Eligibility criteria

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 (Type1 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

South Korea · 61 centers

• Seoul National University Hospital — Seoul
• Andong Hospital — Andong
• Dong-A University Hospital — Busan
• Inje University Busan Paik Hospital — Busan
• Kosin University Gospel Hospital — Busan
• Pusan National University Hospital — Busan
• Gyeongsang National University Changwon Hospital — Changwon
• Soonchunhyang University Cheonan Hospital — Cheonan
• … and 53 more centers

Publications

• 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. PMID 19944261
• 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. PMID 9355934
• Ajani UA, Ford ES, Greenland KJ, Giles WH, Mokdad AH. Aspirin use among U.S. adults: Behavioral Risk Factor Surveillance System. Am J Prev Med. 2006 Jan;30(1):74-7. doi: 10.1016/j.amepre.2005.08.042. PMID 16414427
• 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. PMID 24573704
• 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/eurhear PMID 30165437
• 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. Effe PMID 30221597
• 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 PMID 30146931
• 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: 10.101 PMID 30158069

Identifiers

NCT: NCT05845489 · H-2212-044-1385

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗