Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Randomized Trial of Warfarin Plus Antiplatelet Therapy Versus Antiplatelet Therapy Alone in Patients With Peripheral Vascular Disease
Brief Summary: The purpose of this study is to evaluate whether the addition of warfarin (a blood-thinning medication) to an antiplatelet therapy like aspirin is better than antiplatelet therapy alone (i.e. usual treatment) for the prevention of leg surgery, heart attacks, stroke and death in people with peripheral vascular disease.


Options:
A: Inclusion Criteria:

* Confirmed acute symptomatic DVT, i.e. proximal or extensive calf-vein thrombosis involving at least the upper third part of the calf veins, without concomitant symptomatic PE
* Written informed consent

Exclusion Criteria:

* Legal lower age limitations (country specific)
* Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT
* Other indication for VKA than PE/DVT
* More than 36 hours pre-randomization treatment with therapeutic dosages of (LMW) heparin or more than a single dose of VKA prior to randomization
* Participation in another pharmacotherapeutic study within the prior 30 days
* Creatinine clearance \< 30 mL/min, impaired liver function (transaminases \> 2 x ULN), or bacterial endocarditis
* Life expectancy \< 3 months
* Active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin
* Uncontrolled hypertension: systolic blood pressure \> 200 mmHg and diastolic blood pressure \> 110 mmHg
* Pregnancy or childbearing potential without proper contraceptive measures
* Any other contraindication listed in the labeling of warfarin, acenocoumarol, phenprocoumon, fluindione, UFH, enoxaparin, or tinzaparin
* Systemic treatment with azole compounds or other strong CYP3A4 inhibitors (e.g. ketoconazole, fluconazol, itraconazole, HIV protease inhibitors) within 4 days prior to randomization and during the study
B: Inclusion Criteria:

* Women and men 55 years of age or over with established CVD and at high risk for future fatal and nonfatal CV events, defined as:

  1. Documented coronary artery disease (CAD);
  2. Documented peripheral vascular disease (PVD);
  3. Documented cerebrovascular disease;
  4. Diabetes with one of the following; additional cardiovascular risk factors:

  i) hypertension (BP \>160 mmHg systolic or \>90 mmHg diastolic or on treatment); ii) total cholesterol \>5.2 mmol/L (\>200 mg/dl); iii) HDL cholesterol \<0.9 mmol/L (3.5 mg/dl); iv) current cigarette smoker; v) any evidence of previous vascular disease
* Provision of informed consent

Exclusion Criteria:

* Current use of any vitamin supplements containing folic acid \>200 micrograms/day. The patients taking such vitamin supplements can be asked if they agree to discontinue these supplements. If they agree, they can be randomized to the study following a one month wash-out period.
* Known previous adverse reactions to folic acid and/or vitamin B6 and/or B12.
* Planned cardiac, peripheral or cerebrovascular revascularization, defined as a decision taken by the patient and his or her physician(s) to perform surgical or percutaneous transluminal revascularization within the next 6 months.
* Hemodynamically significant primary valvular outflow tract obstruction (e.g. mitral stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic valve).
* Constrictive pericarditis.
* Complex congenital heart disease.
* Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias (asymptomatic arrhythmias including ventricular tachycardia are not exclusion criteria.
* Uncontrolled hypertension.
* Cor pulmonale.
* Heart transplant recipient.
* Other important non-cardiovascular disease(s) expected to limit compliance and/or impact on patient's ability to complete the study, such as: \*history of alcohol or drug abuse, \*psychiatric disorders, \*senility, \*severe physical disability, \*illnesses including terminal stage of cancer and other major systemic illnesses expected to limit the patient's ability to comply with the study protocol and to complete the study.
C: Inclusion Criteria:

* Patients with confirmed symptomatic PE or DVT who have been treated for 6 or 12 months with VKA or rivaroxaban

Exclusion Criteria:

* Legal lower age limitations (country specific)
* Indication for VKA other than DVT and/or PE
* Patients in whom anticoagulant treatment for their index PE or DVT should be continued
* Childbearing potential without proper contraceptive measures, pregnancy or breast feeding. Proper contraceptive measures are defined as a method of contraception with a failure rate \< 1 % during the course of the study (including the observational period). These methods of contraception according to the note for guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP \[Committee for Proprietary Medicinal Products\]/ICH \[International Conference on Harmonization\]/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence and vasectomy
D: Inclusion Criteria:

* Intermittent claudication with objective evidence of PVD (e.g. ankle-brachial index \[ABI\] \< 0.90)
* Ischemic rest pain of the lower limbs
* Ischemic non-healing ulcers or focal gangrene
* Amputation for vascular causes
* Previous peripheral vascular revascularization (angioplasty or bypass surgery)
* Blue toe syndrome
* Other significant peripheral arterial disease (e.g. carotid stenosis)
* Vascular disease and evidence of asymptomatic peripheral arterial disease \[PAD\] (i.e. ABI \< 0.90)

Exclusion Criteria:

Temporary:

* Potential subjects will be temporarily excluded if they need to undergo:

  * vascular diagnostic (angiography) or interventional procedures (arterial bypass graft surgery or angioplasty); or
  * limb amputation for vascular insufficiency.

Permanent:

* Subjects will be excluded for the following:

  * active bleeding or high risk bleeding;
  * clear indication for long-term warfarin use (i.e. atrial fibrillation);
  * previous allergy or intolerance to warfarin;
  * stroke in the last 6 months;
  * renal failure requiring dialysis;
  * known significant abdominal aortic or cerebral aneurysm;
  * peripheral arterial aneurysms (iliac or femoral) without evidence of lower limb ischemia;
  * significant liver disease (i.e. cirrhosis);
  * cancer with a life expectancy \< 6 months;
  * anticipated non-adherence to warfarin;
  * excessive alcohol use;
  * pregnancy or planning to become pregnant; or
  * failure to provide informed consent.

Answer: D