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:

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
B: Inclusion Criteria:

* Patients with TIA or minor acute ischemic stroke (NIHSS \< 4 at the time of randomization) who must NOT be candidates for acute thrombolysis or other acute intervention indicated as the current standard of care
* Aged 40 years or older
* Patients with: (a) weakness at time of TIA/minor stroke and/or language disturbance at time of TIA/minor stroke and; (b) duration of neurological deficit (TIA) \> 5 minutes
* Patients can be randomized within 24 hours of symptom onset. Symptom onset is defined by the "last seen well" principle
* Patients must have provided written, informed consent to participate in the FASTER trial.

Exclusion Criteria:

* Patients with pure sensory symptoms, pure vertigo or dizziness, pure ataxia or pure visual loss
* Patients for whom thrombolysis or other acute intervention is indicated as the current standard of care
* Patients who are currently on statin therapy, antiplatelet therapy (not including aspirin), or long-term non-steroidal anti-inflammatory drugs (NSAIDs but not COX inhibitors), or anticoagulation
* Patients who in the opinion of the site Investigator, should be commenced on statin therapy
* Patients with neurological deficit due to intracranial hemorrhage (intracranial hemorrhage, subarachnoid hemorrhage, subdural hematoma, epidural hematoma), tumor, infection or any finding not consistent with acute brain ischemia as the cause of presenting symptoms
* Presumed cardiac source of embolus (e.g. atrial fibrillation, prosthetic cardiac valve, known/suspected endocarditis)
* Patient with a concomitant acute coronary syndrome (acute myocardial infarction or unstable angina)
* Modified Rankin Score 3 or more (pre-morbid historical assessment)
* Patients in whom the qualifying event was due to a complication of cerebral angiography, a revascularization procedure or trauma
* Uncontrolled hypertension at baseline (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg), or malignant hypertension defined by brain plus acute organ involvement due to acute hypertension
* Women who are breast-feeding or pregnant. Women of childbearing potential must have a negative pregnancy test prior to randomization. Women of childbearing potential may still participate in the trial but must plan on not becoming pregnant during the course of the study and must practice a suitable method of birth control. If a patient becomes pregnant or begins breast-feeding during the study, both study drugs will be discontinued immediately, and the patient followed for the duration of the study
* Evidence of contraindication for use of Trial Medication: (i) serious systemic bleeding precluding antiplatelet therapy; (ii) hypersensitivity to aspirin, thienopyridine drugs (clopidogrel or ticlopidine) or statins; (iii) current or past history of renal insufficiency \[serum Creatinine \>150 umol\]; (iv) hepatic dysfunction indicated by any or all of the following \[ALT \>3xULN, AST \>3xULN, ALP \>3xULN\]; (v) thrombocytopenia \[platelet count \< 150 x10\^9/L\]; (vi) neutropenia \[neutrophil count \< 0.5 x10\^9/L\]; (vii) bleeding diathesis or coagulopathy indicated by any or all of the following \[INR \>1.2, PT \>1.2xULN, PTT \>1.2xULN\]
* Life expectancy of less than 90 days
* Participation in another clinical therapeutic trial (drug or device) either concurrently or within the previous 30 days, or prior participation in FASTER
* Geographical or other factors that render follow-up impractical or that render evaluation of outcome events impossible (e.g. severe dementia). Patients may be randomized who could and are willing to complete their follow-up at a participating centre
C: Inclusion Criteria:

1. Among consecutive patients treated with DES, event-free patients who survived at least the first 12 months without nonfatal MI or repeat revascularization
2. The patient or guardian agrees to the study protocol and the schedule of clinical follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site.

Exclusion Criteria:

1. Contraindication to antiplatelet therapy (aspirin or clopidogrel)
2. Non-cardiac co-morbid conditions are present with life expectancy \<1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
3. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.
4. Concurrent bleeding diathesis or major bleeding history requiring discontinuation of antiplatelet drugs.
5. Patients with left main stem stenosis (\>50% by visual estimate) or left main stenting
6. Concomitant disease requiring long-term use of clopidogrel (stroke, peripheral vascular disease, significant carotid a. disease, etc)
D: Inclusion Criteria:

* Documented stable Coronary Artery Disease (stable angina, previous MI history, previous history of revascularization);
* Females of child bearing potential must have a negative pregnancy test prior to receiving study drug and be willing to use a hormonal contraceptive in addition to double barrier contraception

Exclusion Criteria:

* History of Acute Coronary Syndromes within 12 months of screening or need for revascularization (angioplasty or Coronary Artery Bypass Graft (CABG))
* History of liver or kidney disease
* Have increased bleeding risk, eg, recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count, recent major trauma
* History of intolerance or allergy to Aspirin or clopidogrel

Answer: A