Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Parallel Randomized Controlled Evaluation of Clopidogrel Plus Aspirin, With Factorial Evaluation of Irbesartan, for the Prevention of Vascular Events, in Patients With Atrial Fibrillation
Brief Summary: The purpose of this study is to determine if the combination of Clopidogrel 75mg once daily (od) plus aspirin at 100mg daily (recommended dose) is as effective as oral anticoagulation therapy with a lower risk of bleeding in patients with atrial fibrillation associated with at least one major cardiovascular risk factor.Primary objectives :The combination of clopidogrel plus aspirin compared to adjusted dose (INR between 2.0 and 3.3) oral anticoagulation (a vitamin K antagonist) will result in the same risk of the composite outcome of stroke, non-CNS systemic embolism, myocardial infarction or vascular death in patients with atrial fibrillation.The secondary objective is to establish whether or not aspirin plus clopidogrel has a lower risk of hemorrhage than standard anticoagulation therapy.


Options:
A: Inclusion Criteria:

* Patients must have documented atrial fibrillation on 2 separate occasions within 6 months before screening
* History of a prior stroke, transient ischemic attack or non-neurologic systemic embolism believed to be cardiac in origin, or at least two of the following risk factors: heart failure, hypertension, age 75 years or greater, diabetes mellitus

Exclusion Criteria:

* Significant mitral stenosis
* Transient atrial fibrillation caused by a reversible disorder
* Active internal bleeding
* Severe disabling stroke
* History of intracranial bleeding
* Hemorrhagic disorders
B: Inclusion criteria:

* Patients scheduled to undergo primary, unilateral, elective total hip arthroplasty.
* Male or female 18 years of age or older.
* Patients giving written informed consent for study participation.

Exclusion criteria:

* Patients weighing less than 40 kg.
* History of bleeding diathesis.
* Patients who in the investigators judgement are perceived as having an excessive risk of bleeding, for example, constitutional or acquired coagulation disorders or because of anticipated need of quinidine, verapamil or other restricted medication during the treatment period (see Section 4.2.2).
* Major surgery or trauma (e.g., hip fracture) within 3 months of enrolment.
* Recent unstable cardiovascular disease (in the investigators opinion) such as uncontrolled hypertension, that is ongoing at the time of enrolment or history of myocardial infarction within 3 months of enrolment.
* Any history of haemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, Atriovenous (AV) malformation or aneurysm.
* Ongoing treatment for Venous Thromboembolism (VTE).
* Clinically relevant bleeding (gastrointestinal, pulmonary, intraocular or urogenital bleeding) within 6 months of enrolment.
* Gastric or duodenal ulcer within one year of enrolment.
* Liver disease expected to have any potential impact on survival (ie, hepatitis B or C, cirrhosis). This does not include Gilberts syndrome or hepatitis A with complete recovery.
* Active liver disease or liver disease decreasing survival (e.g, acute hepatitis, chronic active hepatitis, cirrhosis) or Alanine Aminotransferase (ALT) \>3 x ULN.
* Known severe renal insufficiency (CrCl \<30 ml/min). Note: CrCl should be calculated only if serum creatinine is elevated or renal insufficiency is suspected. See Appendix 10.1 for calculation.
* Elevated creatinine that, in the investigators opinion, contraindicates venography.
* Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin \>162.5 mg/day or NSAID with t 1/2 \>12 hours within 7 days prior to hip replacement surgery OR anticipated need while the patient is receiving study medication and prior to 24 hours after the last administration of any blinded study medication (COX-2 selective inhibitors are allowed).
* Anticipated required use of intermittent pneumatic compression and electric stimulation of lower limb.
* Pre-menopausal women (last menstruation within 1 year prior to signing informed consent) who:

  * Are pregnant.
  * Are nursing.
  * Are of child-bearing potential and are NOT practicing acceptable methods of birth control, or do NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control include intrauterine device; oral, implantable or injectable contraceptives and surgical sterility.
* Known allergy to radio opaque contrast media.
* History of thrombocytopenia, including heparin-induced thrombocytopenia, or a platelet count \<100,000 cells/microliter at randomisation.
* Allergy to heparins or dabigatran etexilate.
* Active malignant disease or current cytostatic treatment. Patients should be disease free for at least 5 years.
* Participation in a clinical trial within 30 days of randomisation.
* Leg amputee.
* Known alcohol or drug abuse which would interfere with completion of the study.
* Contraindications to enoxaparin.
* Previous participation in this study.
C: Inclusion Criteria:

* Evidence of atrial fibrillation either on one current Electrocardiogram (ECG) or on two ECG recorded at two weeks a part during 6 months prior to study enrollment.
* Evidence of high risk of vascular events: at least one of the following risk criteria must be present:

  * are 75 years or greater;
  * on treatment for systemic hypertension;
  * prior stroke, TIA, or non-CNS systemic embolus;
  * left ventricular dysfunction with left ventricular ejection fraction (EF) estimated by echocardiogram or angiogram (radionuclide or contrast) to be \< 45%;
  * peripheral vascular disease (previous peripheral artery revascularization, limb and foot amputation, or the combination of current intermittent claudication and ankle arm systolic blood pressure ratio \< 0.9);
  * age 55 to 74 years; AND
  * either diabetes mellitus requiring drug therapy, or documented previous myocardial infarction, or documented coronary artery disease.

Exclusion Criteria:

* Patients will be excluded from ACTIVE if any of the following are present :

  * requirement for clopidogrel (such as recent coronary stent procedure);
  * requirement for oral anticoagulant (such as prosthetic mechanical heart valve);
  * prior intolerance to ASA or clopidogrel;
  * documented peptic ulcer disease within the previous 6 months;
  * prior intracerebral hemorrhage;
  * significant thrombocytopenia; (platelet count \< 50 x 10(9)/L);
  * psychosocial reason making study participation impractical;
  * geographic reason making study participation impractical;
  * ongoing alcohol abuse;
  * mitral stenosis;
  * pregnant or nursing woman or woman of child bearing potential and not on effective birth control for at least one month prior to start of study or not willing to continue on birth control for duration of study;
  * severe comorbid condition such that the patient is not expected to survive 6 months;
  * patient currently receiving an investigational pharmacologic agent; OR
  * requirement for chronic (\> 3 months) non-COX-2 inhibitor NSAID therapy.
D: Inclusion criteria:

1. Patients aged 18-75
2. Patients who have received a bileaflet mechanical heart valve

Exclusion criteria:

1. Prior valve surgery
2. Uncontrolled hypertension
3. severe renal impairment
4. active liver disease
5. increased risk of bleeding

Answer: C