Please select the eligibility criteria that correspond to the clinical trial below.
Title: Secondary Prevention of Small Subcortical Strokes (SPS3) Trial
Brief Summary: The goal of this study is to learn if combination antiplatelet therapy (aspirin and clopidogrel) is more effective than aspirin alone for the prevention of recurrent stroke and cognitive decline, and if intensive blood pressure control is associated with fewer recurrent strokes and cognitive decline.

On July 21, 2011 the DSMB recommended terminating the anti platelet arm of the study due to an imbalance of overall and major non-CNS hemorrhagic SAE's and total deaths in the investigational anti platelet combination of aspirin + clopidogrel and an interim statistical analysis that demonstrated futility in the investigational anti platelet arm. It was recommended that patients be continued on standard care of aspirin mono therapy until their study close-out visit. Also, recommended the continuation and completion of the plood pressure arm following the protocol.


Options:
A: Inclusion Criteria:

* Male or female
* Age 50 to no upper limit
* Hypertension documented according to the 6th report of the Joint National Committee on Detection and Evaluation of the treatment of high BP (JNC VI) and the need for drug therapy (previously documented hypertension in patients currently taking antihypertensive agents is acceptable)
* Documented CAD (e.g., classic angina pectoris (stable angina pectoris; Heberden angina pectoris), myocardial infarction three or more months ago, abnormal coronary angiography, or concordant abnormalities on two different types of stress tests)
* Willingness to sign informed consent

Exclusion Criteria:

* Unstable angina, angioplasty, coronary artery bypass graft surgery (CABG) or stroke within one month. Patients taking beta blockers after myocardial infarction are excluded if study enrollment is planned within 12 months of myocardial infarction. No time limitation if not taking beta-blocker.
* Use of a ß-blocker within past two weeks
* Patients without a pacemaker and any of the following:

  * Sinus bradycardia (\< 50 beats/min.)
  * Sick sinus syndrome
  * Atrioventricular (AV)-block of more than 1st degree
* Documented contraindication to verapamil; documented contraindication to both atenolol and hydrochlorothiazide
* Atrial fibrillation/flutter with Wolff-Parkinson-White (WPW)-Syndrome
* Severe heart failure (New York Heart Association \[NYHA\] IV).
* Concomitant illnesses (e.g., severe renal failure \[Serum creatinine ≥4.0 mg/dl\], severe hepatic failure or known cirrhosis, etc.) which may affect outcome variables or where life expectancy is two years or less or which are likely to require frequent hospitalizations and/or treatment adjustments.
* Patients with psychiatric, cognitive, or social (e.g., alcoholism, etc.) conditions that would interfere with giving consent or cooperating or remaining available for follow-up for two years.
B: 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)
C: Inclusion Criteria:

* acute symptomatic ischemic stroke having relevant lesion on DWI(Diffusion weighted image) MRI 7 days after and 42 days within onset.
* relevant stenosis(more than 50%) or occlusion from MCA(middle cerebral artery)(M1) to distal of ICA(internal carotid artery ) on MR(Magnetic resonance) angiogram or CT angiogram.
* mean systolic blood pressure\>=140mmHg or taking antihypertensive drug on screening.

Exclusion Criteria:

* taking more than 3 antihypertensive drugs and mean systolic blood pressure\>=150mmHg on screening.
* history of recent thrombolysis but stenosis or occlusion remained after thrombolysis.
* evidence of orthostatic hypotension
* suspicious embolic cerebrovascular stenosis
* planned state of cerebrovascular surgery or angioplasty or stent 7 months within screening.
* severe stroke-NIHSS\>=16
* mean systolic blood pressure\>=200mmHg which is not able to control on screening.
* abnormal blood test finding (abnormal LFT(liver function test), anemia, renal insufficiency)
* pregnant or breast-feeding
* severe stroke sequela or medical problem
* suspicious secondary hypertension
* disease causing edema or significant ankle edema on screening.
* severe heart failure which correspond to NYHA (New York Heart Association )heart failure classification class III or IV.
* inappropriate condition determined by investigator
* Patient who do not have FLAIR image on or two months prior to screening.
D: Inclusion Criteria:

* written informed consent to the study
* age \>= 55 years at randomization. There is no upper age limit
* systolic blood pressure \>= 150 mmHg in 2 visits at distance of 7-14 days, irrespective of diastolic pressure. Duration of treatment before visit 1 must be at least 12 weeks
* at least one additional risk factor including the following:
* current cigarette smoking
* total cholesterol \>= 20 mmg/dl, or High Density Lipoproteins (HDL) \< 40 mg/dl, or Low Density Lipoproteins (LDL) cholesterol \>= 130 mg/dl
* family history of cardiovascular disease in male first degree relative \< 55 years or female first degree relative \< 65 years
* previous TIA or stroke
* previous coronary artery disease
* history of peripheral occlusive arterial disease (claudication intermittens associated with angiographic or echographic evidence of \> 60% stenosis)

Exclusion Criteria:

* diabetes (fasting glucose \> 125 mg/dl in two samples or ongoing diabetic treatment)
* renal failure, defined by a serum creatinine \> 2.0 mg/dl
* chronic atrial fibrillation or flutter
* clinically significant hepatic or hematological disorders, alcoholism, drug addiction
* causes precluding ECG interpretation for LVH: complete right or left bundle block, Wolff-Parkinson-White syndrome, previous Q-wave myocardial infarction
* any disease causing reduced life expectancy
* unwilling to participate
* significant (more than traces of) valvular heart disease

Answer: B