Official Title: “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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Parallel Assignment

Study Primary Completion Date: February 2012

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.

Intervention(s) in this Clinical Trial

• Drug: aspirin
  • 325 mg per day
• Drug: Warfarin
  • INR 2.5-3.0; target INR 2.75

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • aspirin
• Active Comparator: 2
  • warfarin

Primary Measures

• Comparison of aspirin and warfarin to determine if either is superior for preventing the combined endpoint of all-cause mortality and stroke in patients with left ventricular ejection fraction <35%.
  • Time Frame: 1 to 6 years
    Safety Issue?: Yes

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Columbia University

Overall Clinical Trial Officials and Contacts

Shunichi Homma, M.D. Principal Investigator Principal Cardiologist, Associate Chief, Division of Cardiology, and Director, Echocardiography Laboratories Professor of Medicine  

Overall Contact: Vilma Mejia (212) 342-6058 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00041938

Study ID Number: U01NS43975-01

ClinicalTrials.gov Identifier: NCT00041938

Health Authority: United States: Federal Government