Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial
Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial
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
Warfarin has proven effective in patients with ischemic heart disease, especially in the
 reduction of stroke, death and re-infarction following myocardial infarction, and in the
 reduction of stroke in atrial fibrillation. Warfarin is the most promising unstudied
 intervention in patients with cardiac failure. This randomized, double-blind, multi-center
 study will define optimal antithrombotic therapy for patients with cardiac (heart) failure
 and patients with low ejection fraction (EF). EF is the proportion of left ventricular volume
 emptied during systole. It reliably measures left ventricular systolic function.

 With the rapidly increasing numbers of elderly patients with heart failure, this study has
 important public health implications. The study will determine which of two commonly used
 treatments Warfarin, an anticoagulant, or aspirin, a drug which affects platelet function is
 better for preventing death and stroke in patients with low ejection fraction.
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.