Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Multinational, Randomized, Parallel Group, Double-blind Trial of Clopidogrel Versus Placebo in High-risk Patients Aged 45 Years and Older, at Risk of Atherothrombotic Events, and Who Are Receiving Background Therapy Including Low-dose ASA.
Brief Summary: RATIONALE:

* Atherothrombosis is a progressive and generalized vascular disease resulting in events leading to myocardial infarction (heart attack), stroke, and vascular death.
* In patients at risk for this disease, it is characterized by an unpredictable, sudden disruption of atherosclerotic plaques, which may lead to total occlusion of artery due to formation of a clot. The use of aspirin (blood thinner agent) for reducing those major ischemic events is either indicated, or recommended by international guidelines. However, aspirin fails to prevent a high percentage of such life-threatening events. Therefore, more effective blood thinning therapy may provide additional clinical benefit to such patients.
* The results of the CURE trial in patients with unstable angina demonstrate the additional benefit of long-term treatment (up to one year) with clopidogrel, (a blood thinner agent), when administered in combination with standard therapy including aspirin. The purpose of CHARISMA is to investigate whether a similar clinical benefit of clopidogrel may apply to a broad population of high-risk patients receiving low-dose aspirin therapy. Such population includes patients with previous cardiovascular, neurovascular or peripheral arterial manifestations of atherothrombosis and patients with combinations of recognized risk factors for atherosclerosis.

OBJECTIVES:

* To assess the efficacy of clopidogrel 75 mg once-daily by comparison with a placebo, in preventing cardiovascular morbidity/mortality. The study will compare the efficacy of the two regimens in preventing the occurrence of major cardiovascular complications (stroke, heart attack, cardiovascular death) in high-risk patients who are otherwise receiving low-dose aspirin therapy (75-162 mg daily).
* To evaluate the safety of clopidogrel in this population, and more specifically the incidence of fatal or severe bleeding (as per GUSTO definition), in order to estimate the global benefit of clopidogrel in this patient population.


Options:
A: Inclusion criteria:

* Adult subjects (male or female≥40 years)
* Acute non-disabling ischemic stroke (NIHSS≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the "last see normal" principle
* TIA (Neurological deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with study drug within 24 hours of symptoms onset and with moderate-to-high risk of stroke recurrence (ABCD2 score≥4 at the time of randomization).Symptom onset is defined by the "last see normal" principle
* Informed consent signed

Exclusion Criteria:

* Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major non-ischemic brain disease (e.g., multiple sclerosis) on baseline head CT or MRI
* Isolated or pure sensory symptoms (e.g., numbness), isolated visual changes, or isolated dizziness/vertigo without evidence of acute infarction on baseline head CT or MRI
* Modified Rankin Scale Score\>2 at randomization (pre-morbid historical assessment)
* NIH Stroke Score≥4 at randomization
* Clear indication for anticoagulation(presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis)
* Contraindication to clopidogrel or ASA
* Known allergy
* Severe renal or hepatic insufficiency
* Severe cardiac failure, asthma
* Hemostatic disorder or systemic bleeding
* History of hemostatic disorder or systemic bleeding
* History of thrombocytopenia or neutropenia
* History of drug-induced hematologic or hepatic abnormalities
* Low white blood cell (\<2 x109/l) or platelet count (\<100 x109/l)
* Use of thrombolysis within 24 hours prior to randomization
* History of intracranial hemorrhage
* Anticipated requirement for long-term non-study antiplatelet drugs, or NSAIDs affecting platelet function
* Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anti coagulation
* Gastrointestinal bleed or major surgery within 3 months
* Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months (if clinically indicated, vascular imaging should be performed prior to randomization whenever possible)
* Scheduled for surgery or interventional treatment requiring study drug cessation
* Qualifying TIA or minor stroke induced by angiography or surgery
* Severe non-cardiovascular comorbidity with life expectancy \< 3 months
* Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test
* Currently receiving an investigational drug or device
B: Inclusion Criteria:

* sign informed consent
* males 45-79 years or females 55-79 years. -Stage 3 or 4 CKD (estimated GFR by MDRD abbreviated, between 15 and 60 ml / min/1.73 m2) -

Exclusion Criteria:

* a previous cardiovascular event: cardiac arrhythmias, cardiac arrest, angina or acute myocardial infarction, stroke, carotid stenosis of more than 50%, peripheral vascular arteriopathy documented
* hospitalization for any cause in the last three months prior to inclusion in the study allergy of acetyl-salicylic acid
* coagulopathy from any cause
* thrombocytopenia \<150,000 platelets
* liver disease from any cause
* Infection by hepatitis B virus, hepatitis C or HIV
* immunosuppressive treatment within 12 weeks before inclusion in the study
* Major bleeding events including gastrointestinal bleeding and brain hemorrhage.
* hemoglobinopathies (eg sickle cell disease or thalassemia of any kind)
* active malignancy (except non-melanoma skin cancer). May be included in the study patients with malignant neoplasia who have remained disease-free for at least the previous 5 years.
* uncontrolled inflammatory disease or symptomatic (eg rheumatoid arthritis, lupus, Chrom disease or bowel inflammatory disease)
* hemolysis
* treatment with oral anticoagulation and / or antiplatelet therapy prior.
* poorly controlled hypertension (\> 160/90 mm Hg) -pregnancy or breast-
* women of childbearing potential not using effective contraception.
C: Inclusion Criteria:

Any one or more of the following:

Meet Angiographic criteria plus

* Systemic hypertension at baseline, or a history of hypertension
* Congestive heart failure at baseline, or a history of CHF
* Renal insufficiency at baseline, or a history of renal insufficiency
* Angina, or a history of angina

Exclusion Criteria:

* Less than 18 years old
* Contraindications to device/drug
D: INCLUSION:

Be at least 45 years old and comply with at least one of the four categories of inclusion criteria:

* Combination of atherothrombotic risk factors (2 major or 3 minor or 1 major + 2 minor risk factors among those listed below)

Major atherothrombotic risk factors

* Type I or II diabetes (under drug therapy)
* Diabetic nephropathy
* Ankle brachial index (ABI) \< 0.9
* Asymptomatic carotid stenosis \>= 70%
* At least one carotid plaque as evidenced by intima-media thickness (IMT)

Minor atherothrombotic risk factors

* Systolic blood pressure (SBP) \>= 150 mmHg, despite appropriate therapy for at least 3 months
* Primary hypercholesterolemia
* Current smoking \> 15 cigarettes per day
* Male \>= 65 years
* Female \>= 70 years

and/or

* Documented cerebrovascular disease (TIA or IS within 5 years) and/or
* Documented coronary artery disease (stable angina with documented multivessel coronary disease, previous documented MI, multivessel PCI or CABG within 1 year, multivessel CABG older than 1 year associated with current angina) and/or
* Documented symptomatic PAD

EXCLUSION:

* Absolute indication for the use of clopidogrel, high-dose aspirin (\>162 mg), NSAIDs, or oral anti-thrombotic drugs
* Absolute contraindication to the use of clopidogrel or aspirin
* Clinical conditions likely to interfere with follow-up leading to inability to complete the trial

Answer: D