Early Single Antiplatelet Therapy After IVUS-Guided PCI in Acute Coronary Syndrome

Major adverse cardiovascular events are defined as a composite of all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, and definite or probable stent thrombosis occurring up to 12 months after randomization.

Clinically relevant bleeding is defined as the incidence of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events occurring up to 12 months after randomization.

TIMI bleeding definitions:

• Major: Any intracranial bleeding (excluding microhemorrhages 10 mm evident only on gradient-echo MRI), clinically overt signs of hemorrhage associated with a drop in hemoglobin of 5 g/dL, Fatal bleeding (bleeding that directly results in death within 7 d)

• Minor: Clinically overt (including imaging), resulting in hemoglobin drop of 3 to 5 g/dL, requiring medical attention, any overt sign of hemorrhage that meets one of the following criteria and does not meet criteria for a major or minor bleeding event, as defined above, requiring intervention (medical practitioner-guided medical or surgical treatment to stop or treat bleeding, including, temporarily or permanently discontinuing or changing the dose of a medication or study drug), leading to or prolonging hospitalization, prompting evaluation (leading to an unscheduled visit to a healthcare professional and diagnostic testing, either laboratory or imaging).

• Major:

• Fatal bleeding and/or
• Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome.

and/or

• Bleeding causing a fall in hemoglobin level of 2 g/dL (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells.
• Minor:

All non-major bleeds will be considered minor bleeds. Minor bleeds will be further divided into those that are clinically relevant and those that are not.

All-cause mortality was used rather than cardiac mortality to eliminate the need for possibly difficult adjudication of causes of death, especially given the relatively low mortality expected.

In addition, the cause of death will be adjudicated as being due to cardiovascular causes, non-cardiovascular causes, or undetermined causes.

• Cardiovascular death includes sudden cardiac death, death due to acute MI, heart failure or cardiogenic shock, stroke, other cardiovascular causes, or bleeding
• Non-cardiovascular death is defined as any death with known cause not of cardiac or vascular causes
• Undetermined cause of death refers to a death not attributable to one of the above categories of cardiovascular death or to a noncardiovascular cause. For this trial all deaths of undetermined cause will be included in the cardiovascular category

The definition of MI is based on the SCAI definition of clinically relevant MI. MI is defined as an abnormal cardiac biomarker level above the institutional upper limit of normal (either cardiac troponin or CK-MB), and either at least 1 of the following: a) Symptoms of myocardial ischemia, b) New or presumed new significant ST-segment-T wave (ST-T) changes or new LBBB on the ECG, c) Development of pathological Q waves on the ECG, d) Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, e) Identification of an intracoronary thrombus by angiography or autopsy.

A coronary revascularization procedure may be either a CABG or a PCI.

• Target Vessel: The target vessel is defined as the entire major coronary vessel proximal and distal to the target lesion including upstream and downstream branches and the target lesion itself All revascularization events will be adjudicated as either ischemia-driven or non-ischemia-driven. Revascularization will be considered ischemia-driven if the diameter stenosis of the revascularized coronary segment is ≥50% by QCA and any of the following criteria for ischemia are met: a) History of angina pectoris, presumably related to the target vessel, b) Objective signs of ischemia at rest (electrocardiographic changes) or during exercise test (or equivalent), presumably related to the target vessel c) Abnormal results of any invasive functional diagnostic test (e.g., CFR or FFR).

• Definite stent thrombosis: defined as occurring when clinical presentation is consistent with acute coronary syndrome and angiography or autopsy examination confirm stent occlusion or thrombus.
• Probable stent thrombosis: defined as death occurring within 30 days that cannot be attributed to another cause or when myocardial infarction occurs at any time point and is attributable to the target vessel in the absence of angiography confirming another culprit lesion.
• Possible stent thrombosis: defined as occurring when the patient dies after >30 days and death is not explained by another cause.

Net adverse clinical events are defined as a composite of major adverse cardiovascular events and clinically relevant bleeding. Major adverse cardiovascular events include all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, and definite or probable stent thrombosis. Clinically relevant bleeding is defined as Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding.

All-cause rehospitalization is defined as any hospital admission occurring after randomization, regardless of cause. Rehospitalization events will be collected during follow-up and classified according to the reason for admission, including cardiovascular, bleeding-related, and non-cardiovascular causes.

Medication adherence is defined as adherence to the assigned antiplatelet treatment strategy during follow-up. At each follow-up visit, antiplatelet therapy status, discontinuation, switching, interruption, and compliance with aspirin, ticagrelor, or prasugrel will be assessed.

Survival rate at 12 months is defined as the proportion of randomized participants who are alive at 12 months after randomization. Vital status will be assessed at follow-up, and deaths will be adjudicated according to cause when available.