Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

NCT ID: NCT00041938

Last Updated: 2014-09-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2305 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-10-31

Study Completion Date

2014-07-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Heart Disease Stroke Ischemic Heart Disease Myocardial Infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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aspirin

Aspirin: 325 mg per day

Group Type ACTIVE_COMPARATOR

aspirin

Intervention Type DRUG

325 mg per day

warfarin

Warfarin: International Normalized Ratio (INR) 2.5-3.0; target INR 2.75

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type DRUG

INR 2.5-3.0; target INR 2.75

Interventions

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aspirin

325 mg per day

Intervention Type DRUG

Warfarin

INR 2.5-3.0; target INR 2.75

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Shunichi Homma

Margaret Milliken Hatch Professor of Medicine at the New York-Presbyterian Hospital at the Columbia University Medical Center (In Biomedical Engineering)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shunichi Homma, M.D.

Role: PRINCIPAL_INVESTIGATOR

Principal Cardiologist, Associate Chief, Division of Cardiology, and Director, Echocardiography Laboratories Professor of Medicine

Seamus Thompson, PhD

Role: PRINCIPAL_INVESTIGATOR

Statistical PI: Clinical Professor of Biostatistics and Neurology

Locations

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Southern Arizona Veterans Affairs Medical Center

Tucson, Arizona, United States

Site Status

University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

Santa Clara Medical Center

Santa Clara, California, United States

Site Status

West Los Angeles Veterans Affairs Medical Center

West Los Angeles, California, United States

Site Status

Denver Health Medical Center

Denver, Colorado, United States

Site Status

Denver Veterans Affairs Medical Center

Denver, Colorado, United States

Site Status

George Washington University

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic Transplant Center

Jacksonville, Florida, United States

Site Status

Melbourne Internal Medicine Associates

Melbourne, Florida, United States

Site Status

Jackson Memorial Hospital/U. of Miami

Miami, Florida, United States

Site Status

Mercy Research Institute

Miami, Florida, United States

Site Status

Cardiovascular Consultants of South Florida

Tamarac, Florida, United States

Site Status

Morehouse School of Medicine

Atlanta, Georgia, United States

Site Status

Northeast Georgia Heart Center

Gainesville, Georgia, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Methodist Heart, Lung and Vascular Institute

Peoria, Illinois, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Louisville Veterans Affairs Medical Center

Louisville, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Gulf Regional Research, LLC

Metairie, Louisiana, United States

Site Status

LSU Health Sciences Center

Shreveport, Louisiana, United States

Site Status

Lahey Clinic

Burlington, Massachusetts, United States

Site Status

Veterans Affairs Medical Center

Detroit, Michigan, United States

Site Status

Mercy Health Partners

Muskegon, Michigan, United States

Site Status

Reno Veterans Affairs Medical Center

Reno, Nevada, United States

Site Status

Concord Hospital

Concord, New Hampshire, United States

Site Status

UMDNJ - New Brunswick

New Brunswick, New Jersey, United States

Site Status

University of Medicine and Dentistry of New Jersey

Newark, New Jersey, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

Buffalo General Hospital

Buffalo, New York, United States

Site Status

Kaleida Health Millard Fillmore Hospital

Buffalo, New York, United States

Site Status

Five Towns Neuroscience Research

Cedarhurst, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Columbia University, New York Presbyterian Hospital PH 3-342

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Northport Veterans Affairs Medical Center

Northport, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Oklahoma City Veterans Affairs Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Lehigh Valley Hospital

Allentown, Pennsylvania, United States

Site Status

Tri-State Medical Group Cardiology

Beaver, Pennsylvania, United States

Site Status

Sewickley Valley Medical Group, Cardiology

Leetsdale, Pennsylvania, United States

Site Status

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Black Hills Health Care System

Fort Meade, South Dakota, United States

Site Status

Brooke Army Medical Center MCHE - MDC Cardiology Service

Fort Sam Houston, Texas, United States

Site Status

Michael E. DeBakey Veterans Affairs Medical Center-MEDVAMC

Houston, Texas, United States

Site Status

Salem VAMC

Salem, Virginia, United States

Site Status

Huntington Veterans Affairs Medical Center

Huntington, West Virginia, United States

Site Status

William S. Middleton Memorial Veterans Hospital

Madison, Wisconsin, United States

Site Status

Center for Neurologic Research

Lethbridge, Alberta, Canada

Site Status

St. Boniface General Hospital

Winnipeg, Manitoba, Canada

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status

Etobicoke Cardiac Research Centre

Rexdale, Ontario, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Montreal General Hospital

Montreal, Quebec, Canada

Site Status

Montreal Heart Institute

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

References

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Corica B, Romiti GF, Simoni AH, Mei DA, Bucci T, Thompson JLP, Qian M, Homma S, Proietti M, Lip GYH; WARCEF Investigators. Educational status affects prognosis of patients with heart failure with reduced ejection fraction: A post-hoc analysis from the WARCEF trial. Eur J Clin Invest. 2024 May;54(5):e14152. doi: 10.1111/eci.14152. Epub 2024 Jan 11.

Reference Type DERIVED
PMID: 38205865 (View on PubMed)

Lee TC, Qian M, Liu Y, Graham S, Mann DL, Nakanishi K, Teerlink JR, Lip GYH, Freudenberger RS, Sacco RL, Mohr JP, Labovitz AJ, Ponikowski P, Lok DJ, Matsumoto K, Estol C, Anker SD, Pullicino PM, Buchsbaum R, Levin B, Thompson JLP, Homma S, Di Tullio MR; WARCEF Investigators. Cognitive Decline Over Time in Patients With Systolic Heart Failure: Insights From WARCEF. JACC Heart Fail. 2019 Dec;7(12):1042-1053. doi: 10.1016/j.jchf.2019.09.003.

Reference Type DERIVED
PMID: 31779926 (View on PubMed)

Teerlink JR, Qian M, Bello NA, Freudenberger RS, Levin B, Di Tullio MR, Graham S, Mann DL, Sacco RL, Mohr JP, Lip GYH, Labovitz AJ, Lee SC, Ponikowski P, Lok DJ, Anker SD, Thompson JLP, Homma S; WARCEF Investigators. Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial. JACC Heart Fail. 2017 Aug;5(8):603-610. doi: 10.1016/j.jchf.2017.04.011.

Reference Type DERIVED
PMID: 28774396 (View on PubMed)

Di Tullio MR, Qian M, Thompson JL, Labovitz AJ, Mann DL, Sacco RL, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Lip GY, Levin B, Mohr JP, Buchsbaum R, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Homma S; WARCEF Investigators. Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial. Stroke. 2016 Aug;47(8):2031-7. doi: 10.1161/STROKEAHA.116.013679. Epub 2016 Jun 28.

Reference Type DERIVED
PMID: 27354224 (View on PubMed)

Freudenberger RS, Cheng B, Mann DL, Thompson JL, Sacco RL, Buchsbaum R, Sanford A, Pullicino PM, Levin B, Teerlink JR, Graham S, Mohr JP, Labovitz AJ, Di Tullio MR, Lip GY, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Homma S; WARCEF Investigators. The first prognostic model for stroke and death in patients with systolic heart failure. J Cardiol. 2016 Aug;68(2):100-3. doi: 10.1016/j.jjcc.2015.09.014. Epub 2015 Nov 6.

Reference Type DERIVED
PMID: 26549533 (View on PubMed)

Homma S, Thompson JL, Qian M, Ye S, Di Tullio MR, Lip GY, Mann DL, Sacco RL, Levin B, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Mohr JP, Labovitz AJ, Buchsbaum R, Estol CJ, Lok DJ, Ponikowski P, Anker SD; WARCEF Investigators. Quality of anticoagulation control in preventing adverse events in patients with heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial substudy. Circ Heart Fail. 2015 May;8(3):504-9. doi: 10.1161/CIRCHEARTFAILURE.114.001725. Epub 2015 Apr 7.

Reference Type DERIVED
PMID: 25850425 (View on PubMed)

Shaffer JA, Thompson JL, Cheng B, Ye S, Lip GY, Mann DL, Sacco RL, Pullicino PM, Freudenberger RS, Graham S, Mohr JP, Labovitz AJ, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Di Tullio MR, Homma S; WARCEF Investigators. Association of quality of life with anticoagulant control in patients with heart failure: the Warfarin and Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Int J Cardiol. 2014 Dec 15;177(2):715-7. doi: 10.1016/j.ijcard.2014.10.012. No abstract available.

Reference Type DERIVED
PMID: 25456692 (View on PubMed)

Homma S, Thompson JL, Sanford AR, Mann DL, Sacco RL, Levin B, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Mohr JP, Massie BM, Labovitz AJ, Di Tullio MR, Gabriel AP, Lip GY, Estol CJ, Lok DJ, Ponikowski P, Anker SD; WARCEF Investigators. Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: a subgroup analysis of WARCEF, a randomized controlled trial. Circ Heart Fail. 2013 Sep 1;6(5):988-97. doi: 10.1161/CIRCHEARTFAILURE.113.000372. Epub 2013 Jul 23.

Reference Type DERIVED
PMID: 23881846 (View on PubMed)

Homma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, Ammon SE, Graham S, Sacco RL, Mann DL, Mohr JP, Massie BM, Labovitz AJ, Anker SD, Lok DJ, Ponikowski P, Estol CJ, Lip GY, Di Tullio MR, Sanford AR, Mejia V, Gabriel AP, del Valle ML, Buchsbaum R; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012 May 17;366(20):1859-69. doi: 10.1056/NEJMoa1202299. Epub 2012 May 2.

Reference Type DERIVED
PMID: 22551105 (View on PubMed)

Other Identifiers

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U01NS039143-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01NS39154

Identifier Type: -

Identifier Source: secondary_id

CRC

Identifier Type: -

Identifier Source: secondary_id

AAAC1093

Identifier Type: -

Identifier Source: org_study_id

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