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WARCEF Trial
Introduction
Warfarin is of proven
efficacy in patients with ischemic heart disease, in particular in the reduction
of stroke, death and re-infarction following myocardial
infarction (MI) and in the reduction of stroke in atrial fibrillation (AF).
There has been little research testing anti-thrombotic agents in patients with
cardiac failure or with left ventricular (LV) systolic
dysfunction and warfarin is the most promising
unstudied intervention in patients with cardiac failure. This project, the
Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction ( WARCEF)
trial, aims to define the place of warfarin and aspirin in the management of
patients with left ventricular systolic dysfunction.
Administrative Centers
WARCEF has two administrative centers:
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the Clinical Coordinating Center (CCC) in the
Department of Cardiology at Columbia University, New York, directed by Shunichi
Homma, M.D.
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the Statistical Analysis
Center (SAC) in the Department of Biostatistics at Columbia University, New
York, directed by JLP (Seamus) Thompson, Ph.D.
The CCC is responsible for all clinical operations of the trial. It identifies, recruits, and manages the
participating clinical sites, and ensures they meet regulatory requirements; and
handles pre-randomization inquiries, ensures eligibility criteria are met,
enrolls patients, ensures that treatment protocols are followed, and responds to
clinical queries and policy issues arising during the trial.
The SAC is responsible for all statistical and data management operations of
the trial. It developed the statistical design and stopping rules, produces
all interim and safety analyses and reviews them with the NINDS-appointed
Data Safety and Monitoring Board (DSMB), and prepares analyses for
publication. It manages data collection, generates data reports for
monitoring bodies, provides datasets for analysis, maintains the trial
website, and backs up and secures all data files.
The Primary Aim
WARCEF is a two-arm (1:1) double-blind
randomized multicenter clinical trial. Its primary aim is to compare the
effectiveness of warfarin and aspirin therapies in heart failure patients,
while taking account of risk of hemorrhage. The primary null
hypothesis is that in patients with EF
≤ 35%, there is no
difference between warfarin (INR 2.5-3.0 with a target INR of 2.75) and
aspirin(325 mg/day) therapies in time to the first to occur of ischemic stroke,
intracerebral hemorrhage (ICH), or death. This is tested against the alternative
hypothesis of a non-zero difference between these two therapies, at
α = .05 twosided, with
power of 80% to detect a 17.82% hazard rate reduction (after appropriate
allowance for crossover and loss to follow-up), with symmetrical stopping and
decision rules. 3201 patients with 2-6 years of follow-up are required.
Any of the three possible outcomes will be clinically important:
If aspirin is better, use of aspirin will be
recommended.
If the evidence is insufficient to declare either
better, use of aspirin will be recommended, given its lower cost and easier administration.
WARCEF is thus expected to be clinically decisive if it is
completed with satisfactory power. WARCEF has power of 80% to detect a 17.82%
hazard rate reduction in the primary outcome (after appropriate allowance for
crossover and loss to follow-up). 3201 patients with 2-6 years of follow-up are
required.
Inclusion criteria
- Cardiac EF ≤35% by
radionucleide ventriculography, left ventriculography or quantitative
echocardiographic measurement or
an echocardiographic Wall Motion Index of
≤1.2, within
three months of 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.
Study Medication
Each randomized patient receives two medications. The first
medication is either a 2 mg warfarin tablet, or an identical appearing placebo
tablet. The second medication is either a 325 mg aspirin tablet, or an identical
appearing placebo tablet. Patients assigned to the warfarin treatment arm will
receive warfarin and placebo aspirin. Likewise, patients assigned to the aspirin
treatment arm will receive placebo warfarin and aspirin.
Return to Main Echo
Page
Please e-mail
zqz1@columbia.edu
with any general questions.
This Web site is currently maintained by Michael Zhang.
© New York Presbyterian Medical Center, Adult Echocardiography Lab, Columbia
University
Last revised
02/29/2008
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