Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised Controlled Trial of a Fixed-dose Combination Polypill Medication (the Red Heart Pill) and Usual Care in Those at High Risk of Cardiovascular Disease.
Brief Summary: People with established cardiovascular disease need secondary prevention that addresses multiple risk factors. Complexity \& cost confer particularly difficult barriers to uptake of treatment; recovery from a stroke or heart attack typically necessitates multiple drugs for cholesterol, blood pressure and platelet function. A low-cost, fixed-dose, once-daily combination polypill, the Red Heart Pill, has been formulated by Dr Reddy's Laboratories. UMPIRE will evaluate whether provision of this polypill compared with usual medications improves adherence and clinical outcomes among high-risk patients in Europe and India. The results will be used to develop recommendations for equitable access.


Options:
A: Inclusion Criteria:

* Adults (≥ 18 years)
* The participant is able to give informed consent.
* Established atherothrombotic cardiovascular disease (CVD) or high cardiovascular risk, of for individuals without established cardiovascular disease, a calculated 5 year CVD risk of 15% or greater (calculated using the 1991 Anderson Framingham risk equation with adjustments as defined by the New Zealand Guidelines Group recommendations)
* The trial Investigator considers that each of the polypill components are indicated
* The trial Investigator is unsure as to whether a polypill-based strategy or usual care is better.

Exclusion Criteria:

* Contraindication to any of the components of the polypill (e.g. known intolerance to aspirin, statins, or ACE inhibitors,pregnancy or likely to become pregnant during the treatment period).
* The treating doctor considers that changing a participant's cardiovascular medications would put the participant at risk (e.g. symptomatic heart failure, high dose βblocker required to manage angina or for rate control in atrial fibrillation,accelerated hypertension, severe renal insufficiency, a history of severe resistant hypertension)
* Known situation where medication regimen might be altered for a significant length of time, e.g. current acute cardiovascular event, planned coronary bypass graft operation.
* Unlikely to complete the trial (e.g. lifethreatening condition other than cardiovascular disease) or adhere to the trial procedures or attend study visits (e.g. major psychiatric condition, dementia).
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:

-Clinical diagnosis of ischaemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze, vision or neglect. Symptoms must be distinguishable from an episode of generalised ischaemia (i.e. syncope), seizure, or migraine disorder.

Main inclusion criteria:

* Patients at risk of stroke who have had transient ischaemia of the brain or completed ischaemic stroke due to thrombosis
* Symptoms of ischaemic attack began less than 24 hours prior to study medication start, are to be present for at least 30 minutes and have not significantly improved before start of treatment
* Patients are eligible for platelet inhibiting treatment
* National Institute of Health Stroke Scale (NIHSS) between 5 and 20 (at pre-screening and screening)
* Actual Modified Rankin Scale (mRS) (at baseline) is worse than retrospective mRS (before stroke)
* A contraindication for stroke lysis is given
* Patients are able to give (at least oral) informed consent and to swallow either medication

Exclusion Criteria:

* Hypersensitivity to any of the components of the product or salicylates.
* Patients with active gastric or duodenal ulcers or with bleeding disorders.
* Pregnancy during the third trimester.
* Lysis therapy.
* A platelet inhibiting therapy with Acetylsalicylic Acid (ASA) doses of more than 100 mg per day, or with clopidogrel of any dose has been planned or started.
* Time of onset of stroke symptoms is unknown (when a stroke happened during night-/sleeping time, bedtime is assumed as time of onset)
D: Major Inclusion Criteria:

* Age 18-60 years inclusive.
* Positive contrast valsalva bubble study by trans-esophageal echocardiogram (TEE) for patent foramen ovale (PFO), with or without atrial septal aneurysm.
* Stroke or clinically definite TIA (contact study coordinator).
* Be able to comply with follow up over two years.
* Be competent to, or have a legal guardian competent to, provide informed consent following full disclosure of risks and benefits of both treatment arms by a study investigator.
* Venous access capable of accepting a 10F minimum vascular sheath.
* Have, or be willing to, discontinue hormonal based contraceptive use prior to enrollment and for the term of the study.
* Has cardiac anatomy based on enrollment echocardiogram that will allow for placement of the implant if randomized to the implant arm.
* Note: Additional inclusion criteria may apply. Contact study coordinator or principal investigator for details.

Post-randomization - device patients only

* The size of the PFO (measured by indentation with a soft balloon) must be amenable to selection of a STARFlex device.

Major Exclusion Criteria:

* Carotid artery stenosis \> 50%.
* Intracranial stenosis \> 50% appropriate to symptoms.
* Complex aortic arch atheroma with high risk features for embolism
* Aortic arch, carotid or vertebral artery dissection.
* Mitral or aortic valve stenosis, vegetation, or calcification \> 5 mm mitral annular calcification (MAC) thickness.
* Active pregnancy.
* Active infections (contact study coordinator).
* Active infective endocarditis or bacteremia.
* Prosthetic heart valves in any location.
* Anterior MI within 3 months of neurological event.
* Chronic atrial fibrillation
* Thrombus in, or occluded, venous access route.
* Contraindication to heparin, aspirin, clopidogrel, or warfarin, or a known medical condition that requires continuous warfarin.
* Patient enrolled in another investigation study where clinical endpoint interference may occur.
* Permanent pacemaker or inferior vena cava (IVC) filter.
* Serum creatinine \> 2.0 mg/dL
* Patients with known vasculitis or neurologic disorder.
* Baseline modified Rankin score of 3 or more.
* Hypercoagulopathies requiring long-term warfarin.
* Note: Additional exclusion criteria may apply.

Answer: A