Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial
Condition: Heart Disease; Stroke; Ischemic Heart Disease; Myocardial Infarction
MeSH terms: Heart Diseases; Myocardial Infarction; Myocardial Ischemia; Coronary Artery Disease; Infarction
Intervention: aspirin; Warfarin
Intervention description: 325 mg per day; INR 2.5-3.0; target INR 2.75
Intervention MeSH terms: Aspirin; Warfarin
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2305.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: heart disease; stroke; ischemic heart disease; myocardial infarction; atrial fibrillation; low ejection fraction; cardiac failure; aspirin; Warfarin; anticoagulant

Summary:

      The purpose of this study is to determine which of two treatments, Warfarin or aspirin, is
      better for preventing death and stroke in patients with poor heart function.

      We are now transitioning into the sub-analysis part of the WARCEF patient data.

      The study has recently completed data analysis for its Primary Aim. All randomized patients
      have completed their follow up. All study related procedure as per the protocol has been
      completed. We are now in the extension phase of the study to obtain more patient data to
      address further aims of the study. No new procedures are performed and data already in place
      at the sites will be collected (EKG and echocardiograms).

      The aims for this study extension are:

        -  To assess progression of cardiac dysfunction over time among heart failure patients

        -  To correlate prognosis with cardiac dysfunction
    

Eligibility criteria:

        Inclusion Criteria

          -  Cardiac EF <=35% by radionuclide ventriculography, left ventriculography or quantitive
             echocardiographic measurement or an echocardiographic Wall Motion Index of <=1.2,
             within three months of enrollment. The patient's clinical cardiac state at enrollment
             should be similar to their state at the time of the qualifying echocardiogram. The
             qualifying left ventricular function measurement must be obtained at least three
             months after an MI, coronary bypass grafting, PTCA, and at least one month after
             pacemaker insertion. Patients scheduled for mitral valve repair should have qualifying
             echo after surgery.

          -  Modified Rankin score <=4.

          -  Patient must be taking ACE inhibitors. If intolerant of ACE inhibitor, patient must be
             on angiotensin II receptor blockers or hydralazine and nitrates.

          -  Patient is able to follow an outpatient protocol (requiring monthly blood tests and
             clinic visits every four months for the duration of the study) and is available by
             telephone.

          -  Patient understands the purpose and requirements of the study, can make him/herself
             understood, and has provided informed consent.

          -  Patients with recent stroke or TIA within twelve (12) months will be eligible to be
             included in the recent stroke (RS) subgroup.

          -  Chronic CHF patients (NYHA I * IV) admitted to the hospital can be randomized prior to
             discharge if the patient is stable, taking oral medications for 24 hours and
             ambulatory at the time of discharge. Stable New York Heart Association Class IV
             patients will be eligible for randomization.

        Exclusion Criteria

          -  The presence of any of the following unequivocal cardiac sources of embolism: chronic
             or paroxysmal AF, mechanical valve, endocarditis, intracardiac mobile or pedunculated
             thrombus, and valvular vegetation.

          -  Cyanotic congenital heart disease, Eisenmenger's syndrome.

          -  Decompensated heart failure.

          -  Cardiac surgery, angioplasty, or MI within the past 3 months prior to randomization.

          -  A contraindication to the use of either warfarin or aspirin, e.g. active peptic ulcer
             disease, active bleeding diathesis, platelets <100,000*, hematocrit <30, INR >1.3 (if
             not on warfarin), clotting factor abnormality that increases the risk of bleeding,
             alcohol or substance abuse, severe gait instability, cerebral hemorrhage, systemic
             hemorrhage within the past year, severe liver impairment (AST >3x normal*, cirrhosis),
             any condition requiring regular use of non-steroidal anti-inflammatory agents, allergy
             to aspirin or warfarin, uncontrolled severe hypertension (systolic pressure >180 mm Hg
             or diastolic pressure > 110 mm Hg), positive stool guaiac not attributable to
             hemorrhoids, creatinine >3.0*. *on most recent test done within 30 days prior to
             randomization

          -  Patient needs continuing therapy with intravenous heparin or low molecular weight
             heparin or a specific antiplatelet agent.

          -  Dementia or psychiatric or physical problem that prevents the patient from following
             an outpatient program reliably.

          -  Comorbid conditions that may limit survival to less than five years.

          -  Pregnancy, or female of childbearing potential who is not sterilized or is not using a
             medically accepted form of contraception* (see procedure manual). *A pregnancy test is
             required for all women of childbearing age.

          -  Enrollment in another study that would conflict with WARCEF.

          -  Hospitalization for new diagnosis of onset CHF within the past one month or carotid
             endarterectomy or pacemaker insertion within the past one month prior to randomization
             .

          -  Person under 18 years of age.