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:

* A person who has been diagnosed with acute coronary syndrome and is to undergo a percutaneous coronary intervention.
* A person who is of the legal age of 18 and is mentally competent to provide a signed written informed consent.
* If a woman is of childbearing potential (i.e., before menopause), she must test negative for pregnancy and agree to use a reliable method of birth control.

Exclusion Criteria:

* A person who has had an ischemic stroke within the last 3 months or a hemorrhagic stroke at any time in the past.
* A person who has active internal bleeding or has a history of a bleeding disorder.
* Individuals who are at an increased risk of bleeding based on laboratory criteria evaluated by the treatment physician or on medication that can cause bleeding.
* A person who has liver disease; for example, cirrhosis.
* A person who has a condition such as alcoholism, mental illness, or is drug dependent.
* A person who has cardiogenic shock, a refractory ventricular arrhythmia, or congestive heart failure (class IV).
B: Inclusion Criteria:

* Patients presenting in the participating hospitals with a TIA or non-disabling stroke of atherosclerotic origin
* Randomisation within 6 months after the TIA or minor stroke
* Modified Rankin scale of 3 or less

Exclusion Criteria:

* (Contra)indication to, or intolerance to, anticoagulants, dipyridamole, or aspirin
* Disease expected to cause death within weeks or months
* Source of embolism in the heart
* Moderate or severe ischemic damage to the white matter of the brain (leukoaraiosis)
* Anemia, polycythemia, thrombocytosis, or thrombocytopenia
* Planned carotid endarterectomy
* Intracranial bleeding or cerebral tumour
* TIA or stroke caused by vasculitis, migraine, or dissection
* Severe hypertension
* Liver failure
* Pregnancy
* Chronic alcohol abuse
C: Inclusion Criteria:

Inclusion Criteria:

* Patients with NYHA class II, III, or IV and left ventricular ejection fractions less than or equal to 35%, on an ACE inhibitor (unless not tolerated) and on a diuretic.

Exclusion Criteria:
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