Efficacy and Safety of Aspirin in Patients with Chronic Coronary Syndromes Without Revascularization (ASA-IN)

The purpose of this study is to evaluate the efficacy and safety aspirin in patients with chronic coronary syndromes without revascularization.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Ischemic Heart Disease; Stable Angina Pectoris
• Intervention / Treatment: Drug: Aspirin; Drug: No aspirin

Detailed Description

Aspirin for secondary prevention in the acute phase of acute coronary syndromes has been established. Although it is still disputable about the duration, there is also a consensus for antiplatelet therapy in patients after percutaneous coronary revascularization. On the other hand, several large randomized clinical trials (RCTs) have shown that aspirin treatment for primary prevention of cardiovascular events increases bleeding events and does not provide net clinical benefit.Patient with chronic coronary syndromes (CCS) but not eligible for revascularization do not belong to any of these categories and there is no evidence on the efficacy of aspirin in this population. Therefore, we designed a multicenter, randomized, open-label study to evaluate the efficacy and safety of aspirin in patients with CCS who are not eligible for revascularization.

• Study Type: Interventional
• Enrollment (Estimated): 2890
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Takeshi Kimura, MD, PhD; Phone Number: +81-75-751-4255; Email: taketaka@kuhp.kyoto-u.ac.jp
• Study Contact Backup: Name: Erika Yamamoto, MD, PhD; Phone Number: +81-75-751-4255; Email: erkymmt@kuhp.kyoto-u.ac.jp

Study Locations

• Japan
  • Kyoto, Japan
    • Recruiting
    • Kyoto University Hospital
    • Contact: Erika Yamamoto, MD, PhD; Phone Number: +81-75-751-4255; Email: erkymmt@kuhp.kyoto-u.ac.jp
    • Contact: Takeshi Kimura, MD, PhD; Phone Number: +81-75-751-4255
    • Contact: Takeshi Kimura, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with chronic coronary syndromes with ≧50% diameter stenosis in one or more major coronary vessels/major branches on coronary CT or coronary angiography but not eligible for coronary revascularization
• Patients for whom consent can be obtained

Exclusion Criteria:

• Patients with history of acute coronary syndromes (ACS)
• Patients with history of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)
• Patients with left main trunk stenosis (≥50%)
• Patients for whom aspirin administration is mandatory
• Patients undergoing antithrombotic therapy other than aspirin
• Patients with atrial fibrillation
• Patients with history of stroke within six months
• Patients scheduled for major surgical procedures that will require aspirin discontinuation
• Patients with contraindication of aspirin
• Patients expected to have a prognosis of 1 year or less due to comorbidities
• Women of child-bearing potential or women who have a positive pregnancy test at enrolment or randomization
• Patients who are judged by attending physicians to be inappropriate to participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspirin; Aspirin 100 mg/day	Drug: Aspirin; Aspirin 100 mg/day
Active Comparator: No Aspirin	Drug: No aspirin; No aspirin administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite cardiovascular events	Composite of all-cause death, myocardial infarction, ischemic stroke, coronary revascularization, peripheral revascularization, or critical limb ischemia	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	As classified by Academic Research Consortium (ARC) (Circulation. 2007;115:2344-2351).; Cardiac Death: Any death due to proximate cardiac cause, unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment. All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in subjects with coexisting potentially fatal non-cardiac disease should be classified as cardiac.; Vascular Death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause.; Non-cardiovascular Death: Any death not covered by the above definitions such as death caused by infection, malignancy, sepsis, pulmonary causes, accident, suicide or trauma.; Cancer related death: death from cancer cause	5 years
Myocardial infarction	As classified by Academic Research Consortium (ARC): However, the sensitivity is too high for the evaluation with Troponin of the peri-procedural MI, thus CKMB will be used.	5 years
Ischemic stroke	Ischemic stroke is defined as acute onset of a neurological deficit that persists for at least 24 hours and is the result of a disturbance of the cerebral circulation due to ischemia. Deficits that last ≤ 24 hours are due to transient ischemic neurological attack and are not classified in this category.	5 years
Coronary revascularization	The revascularization that meets the following criteria is considered as clinically indicated revascularization. Presence/absence of clinical findings is judged by the operator of the procedure before the revascularization.	5 years
Peripheral revascularization	The revascularization that meets the following criteria is considered as clinically indicated revascularization. Presence/absence of clinical findings is judged by the operator of the procedure before the revascularization.	5 years
Critical limb ischemia	Critical limb ischemia is defined by chronic ischemic pain at rest and/or presence of ischemic skin lesions (gangrene or ulcerations).	5 years
Cardiovascular death	Cardiac Death: Any death due to proximate cardiac cause (e.g. myocardial infarction [MI], low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment. All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Specifically, any unexpected death even in subjects with coexisting potentially fatal non-cardiac disease (e.g. cancer, infection) should be classified as cardiac.; Vascular Death: Death due to non-coronary vascular causes such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular cause.	5 years
Major bleeding	Bleeding/Hemorrhagic Complications will be evaluated using the Bleeding Academic Research Consortium (BARC) definition. Major bleeding is defined as BARC 3 or 5.	5 years
Hospital admission for heart failure	An unplanned hospitalization with heart failure. Heart failure is defined by the modified Framingham criteria as follow: [Major Criteria] 1) Paroxysmal nocturnal dyspnea 2) Orthopnea 3) Neck-vein distension 4) Rales 5) Acute pulmonary edema [Minor Criteria]; Ankle edema; Dyspnea on exertion; Pleural effusion; Tachycardia (HR ≧ 120/min) * For establishing a definite diagnosis of heart failure, 2 Major criteria or 1 major and 2 minor criteria must be present concurrently	5 years
Cancer incidence	Non-metastatic cancer (not present prior to randomization); Metastatic cancer (cancer that was metastatic at presentation, metastasis of a non-metastatic cancer presents at baseline, or blood cancer) Non-melanoma skin cancer was excluded cancer end points.	5 years
Cancer death	Cancer death is defined as death from cancer cause.	5 years
Composite of all-cause mortality, myocardial infarction, ischemic stroke, coronary revascularization, lower extremity revascularization, critical lower extremity ischemia, major bleeding, hospital admission for heart failure, cancer death	Composite of all-cause mortality, myocardial infarction, ischemic stroke, coronary revascularization, lower extremity revascularization, critical lower extremity ischemia, major bleeding, hospital admission for heart failure, cancer death	5 years

Collaborators and Investigators

• Sponsor: Takeshi Morimoto
• Investigators: Principal Investigator: Takeshi Kimura, MD, PhD, Kyoto University, Graduate School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2022
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 8, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Aspirin; Chronic Coronary Syndrome
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Chest Pain; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Angina Pectoris; Angina, Stable; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Aspirin
• Other Study ID Numbers: Y0126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No