Please select the eligibility criteria that correspond to the clinical trial below.
Title: Dual Antiplatelet Therapy in Patients With Aspirin Resistance Following Coronary Artery Bypass Grafting
Brief Summary: Reactive platelet hyperactivity following coronary artery bypass grafting (CABG) might lead to thrombotic complications and major ischemic cardiac events. The aim of this study is to evaluate the changes in platelet reactivity following CABG and to clarify a potentially beneficial effect of dual antiplatelet therapy in the group of patients with documented aspirin resistance following CABG. Platelet function will be assessed by multiple electrode aggregometry. Aortocoronary vein graft disease is comprised of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia and atherosclerosis. Early vein thrombosis is a major cause of vein graft attrition during the first month after CABG.

Bypass patency can be improved with antiplatelet therapy which is the mainstay of treatment for patients after CABG. A beneficial effect of acetylsalicylic acid (ASA) on vein graft patency has been previously shown. Some patients experience thrombotic events despite continuous aspirin administration after CABG. The investigators hypothesized that low responsiveness to aspirin might be a precipitating factor for adverse thrombotic events following CABG.

Low responsiveness to ASA, as assessed by platelet function tests, varies widely among patients. The etiology of postoperative platelet hyperactivity remains to be elucidated.

In this study a new point-of-care assay named multiple electrode aggregometry (MEA) using a device called Multiplate analyzer (Dynabyte, Munich, Germany) has been utilized. It allows for rapid and standardized assessment of platelet function parameters.

This is a prospective randomized trial. The aim of the study is to document whether introduction of dual antiplatelet therapy in patients with ASA resistance will lead to a lower incidence of major adverse cardiac events (MACE) at a six month follow up. The composite endpoint will include death, non-fatal myocardial infarction, stroke and cardiac rehospitalization. All patients will receive 300 mg of ASA starting 6 hours after surgery, provided that the chest tube output is minimal. On postoperative day 4 their platelet function will be assessed using the above mentioned MEA. The patients found to be aspirin resistant will then undergo the process of randomization. The first arm will include patients with ASA resistance in whom no additional antiaggregation will be administered. In the second arm the investigators will include patients who were randomized to receive 75 mg of clopidogrel in addition to the standard antiplatelet regimen of 300 mg of ASA.

Platelet function monitoring allows for individual tailoring of the antiplatelet therapy. The goal of this study is to define whether this strategy will lead to improved patient outcomes. Both major and minor bleeding complications will be strictly monitored and reported.


Options:
A: Inclusion Criteria:

* Isolated coronary artery bypass grafting
* Patients older than 18 years
* Written informed consent
* Accurate antiplatelet therapy administration documentation

Exclusion Criteria:

* Missing consent
* Patients with cardiac surgical procedures other than isolated CABG
* Antiplatelet therapy other than aspirin 300 mg after CABG
* Previous PCI requiring clopidogrel therapy after CABG
* Patients with unknown preoperative anti-platelet status
* Urgent or emergent surgery
* Off-pump CABG
* Re-Do CABG
* Patients younger than 18 years
B: Inclusion Criteria:

1. Males or females ≥ 18 years of age with coronary artery disease with low, intermediate or high-risk coronary anatomy, which is considered suitable for PCI with stent placement.
2. Subjects who have provided written informed consent prior to initiation of any study-related procedures, prior to receiving any pre-procedural sedation and who agree to comply with all protocol-specified procedures.

Exclusion Criteria:

1. Women who are pregnant. Women of childbearing potential must have a negative pregnancy test (urine or serum HCG) within 7 days prior to randomization; as close to randomization as possible, within 24 hours preferred.
2. Allergy or intolerance to aspirin, or both clopidogrel and ticlopidine
3. Subjects with a contraindication to anticoagulation and/or increased bleeding risk:

   * Past or present bleeding disorder including a history of the following within 1 month prior to randomization: clinically relevant gastrointestinal bleeding, gross (visible) hematuria,
   * Planned major surgery including CABG after or within 1 month prior to randomization.
   * Any subject with a known coagulopathy, platelet disorder, or history of thrombocytopenia.
4. Subjects with a history of cancer (limiting survival) not known to be disease free, with the exception of basal cell carcinoma of the skin.
5. History of clinically important, recent or ongoing alcohol abuse or other drug abuse.
6. Known platelet count \<100,000/mm3 (\<100 x 109/L).
7. Subjects who is unable to give informed consent and assurance for complete contact through 2 years.
C: INCLUSION:

Small subcortical ischemic stroke or subcortical TIA.

Inclusion criteria are based on TOAST criteria supplemented by required MRI data. All of the following criteria must be met:

* One of the lacunar stroke clinical syndromes (adapted from Fisher) lasting \> 24 hrs within the past 6 months
* Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc.
* No ipsilateral cervical carotid stenosis (≥50%) by a reliable imaging modality done in an approved laboratory since the qualifying small subcortical stroke (S3), if hemispheric.
* No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient's primary care physician.
* Subcortical TIA with corresponding lesion on DWI.
* MRI evidence of S3: a. Presence of an S3 (1.5 and 2 cm in diameter corresponding to the qualifying event on DWI; when TIA, ADC image must confirm lesion or T2/FLAIR (hyperintense lesions) (required for all brainstem events) OR multiple S3s on FLAIR/TI(\<1.5 cm in diameter) (hypointense lesions) b. Absence of cortical stroke and large subcortical stroke (recent or remote).

EXCLUSION:

To be eligible for entry into the study, the patient must not meet any of the criteria listed below:

* Disabling stroke (Modified Rankin Scale less than or equal to 4)
* Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke
* Age under 30 years
* High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc)
* Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets
* Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA
* Prior ipsilateral carotid endarterectomy
* Impaired renal function: GFR \<40
* Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR)
* A score \< 24 (adjusted for age and education) on the Folstein Mini Mental Status Examination
* Medical contraindication to MRI
* Pregnancy or women of child-bearing potential who are not following an effective method of contraception
* Geographic or social factors making study participation impractical
* Unable or unwilling to provide informed consent
* Unlikely to be compliant with therapy/unwilling to return for frequent clinic visits
* Patients concurrently participating in another study with an investigational drug or device
* Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic diathesis, drug abuse)
D: Inclusion Criteria: A patient is eligible for inclusion in the study 2-4 days after surgery if all the following criteria are fulfilled:

* Informed consent obtained;
* Chronic background treatment with daily ASA, whatever the dose, started at least 4 weeks before surgery. A window of a few days without ASA before surgery is acceptable, according to local practice. Post-randomization use of ASA must be between 75 and 100 mg/day.
* Unilateral below knee bypass graft (i.e. the distal anastomosis is below the level of the knee joint) for atherosclerotic PAD within the previous 4 days;
* Demonstration of initial patency of the index graft by an objective measurement (e.g. intra-operative Doppler scanning, flow measurement, angiography, Duplex scanning) during bypass surgery, or between surgery and the time of randomization;
* No clinical evidence of graft occlusion at time of randomization.

Exclusion criteria :

PAD medical/surgical history

* Onset of PAD symptoms before the age of 40 years
* Non-atherosclerotic vascular disease (e.g. Buerger's disease, popliteal entrapment syndrome)
* Patient receiving aorto-bifemoral, iliac-femoral or crossover (femoral-femoral) grafts, or undergoing peripheral transcutaneous angioplasty (PTA), with or without stenting, during the same surgery.

Medical history related to bleeding risk

* Current active bleeding at surgical site
* Withdrawal of an epidural catheter less than 12 hours before randomization
* Current active bleeding or increased risk of bleeding, such as severe hepatic insufficiency, proliferative diabetic retinopathy, peptic ulceration, bleeding diathesis or coagulopathy
* Peptic ulceration within 12 months of randomization
* Previous or current intracranial hemorrhage or hemorrhagic stroke, or any previous stroke for which the diagnosis of hemorrhagic stroke cannot be excluded
* Any history of severe spontaneous bleeding such as gastrointestinal bleeding, gross hematuria, intraocular bleeding

Other medical conditions

* Previous disabling stroke (severe cerebral deficit such that the patient is bedridden or demented)
* NYHA Class IV heart failure
* Uncontrolled hypertension: Systolic Blood Pressure (SBP) \> 180 mm Hg, or Diastolic Blood Pressure (DBP) \> 100 mm Hg

Answer: A