The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial,NIVCD
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Transcript of The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial,NIVCD
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JOURNAL PRESENTATION
Presenter:
Dr. Sanjib ChowdhuryMD 3rd part student
Moderator:
Dr. Shafiqur Rahman Patwary
Registrar (Cardiology)
NICVD
1
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Randomized Trial of Warfarin, Aspirin,and Clopidogrel in Patients With Chronic
Heart Failure: The Warfarin andAntiplatelet Therapy in Chronic Heart
Failure (WATCH) Trial.Barry M. Massie, MD; Joseph F. Collins, ScD; Susan E. Ammon, MS, RN, FNP; Paul W.
Armstrong, MD; John G.F. Cleland, MD; Michael Ezekowitz, MD; Syed M. Jafri, MD; William
F. Krol, PhD; Christopher M. OConnor, MD; Kevin A. Schulman, MD; Koon Teo, MD; Stuart R.
Warren, PharmD; for the WATCH Trial Investigators.
Circulation 2009;119;1616-1624; Mar 16, 2009;
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INTRODUCTION
The role of antithrombotic therapy in patients withchronic heart failure has been a subject of debate for
many years.
Different trials found substantial clinical benefit from
anticoagulation, including reductions in embolic
events and deaths.
Heart failure is associated with a hypercoagulable
state and that both sudden deaths and deaths resultingfrom progressive heart failure may be caused by
unrecognized atherothrombotic events.
There exists a clear rationale for anticoagulation in
chronic heart failure.
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Contd.
Many patients with chronic heart failure are treated with
aspirin. There is a belief among physicians that anticoagulation
with warfarin is superior to antiplatelet therapy with
aspirin in preventing major cardiovascular outcomes .
Clopidogrel, an antiplatelet agent with a prostaglandin-
independent mechanism of action, is superior to aspirin in
this population.
The Warfarin and Antiplatelet Therapy in Chronic HeartFailure (WATCH) trial was undertaken to determine the
optimal antithrombotic agent for heart failure patients
with reduced ejection fractions who are in sinus rhythm.
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METHODS
This is a prospective, randomized clinical trial of
open-label warfarin (target international normalized
ratio of 2.5 to 3.0) and double-blind treatment with
either aspirin (162 mg once daily) or clopidogrel (75
mg once daily).
Had a 30-month enrollment period and a minimum of
12 months of treatment.
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This study enrolled 1587 men and women above
18 years of age with-
Symptomatic heart failure for at least 3 months
Patients were in sinus rhythm.
Left ventricular ejection fraction of 35%.
Treated with a diuretic and an ACE inhibitor for
at least 60 days.
Patients were recruited between October 1999
and June 2002 from 142 centers in the United
States, Canada, and the United Kingdom.
Contd.
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The primary end point was the composite of all-
cause mortality, nonfatal MI, and nonfatal stroke.
Secondary end points included the 3 componentsof the primary end point and hospitalizations for
heart failure.
Contd.
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RESULTS
A total of 1587 patients enrolled.
Mean duration of follow-up was 1.9 years
Of the 1587 patients randomized, 523received aspirin, 524 received clopidogrel,
and 540 received warfarin.
The numbers of primary end points weresimilar across treatment groups, as were the
numbers of deaths and nonfatal MIs.
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For the primary composite end point, the hazard ratios were asfollows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to
1.12; P0.77); for clopidogrel versus aspirin, 1.08 (95% CI,
0.83 to 1.40; P0.57); and for warfarin versus clopidogrel, 0.89
(95% CI, 0.68 to 1.16; P0.39).
Warfarin was associated with fewer nonfatal strokes than
aspirin or clopidogrel.
Hospitalization for worsening heart failure occurred in 116(22.2%), 97 (18.5%), and 89 (16.5%) patients treated with
aspirin, clopidogrel, and warfarin, respectively (P0.02 for
warfarin versus aspirin).
Contd.
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There were only 10 total systemic (peripheral arterial,abdominal, renal, pulmonary, and other) embolisms.
There were no significant differences between
treatment groups.
Major bleeding episodes were more frequent in
warfarin patients compared with clopidogrel but not
aspirin patients.
There also were more patients with minor bleeding
episodes in the warfarin group than in the clopidogrel
group and a similar trend in the aspirin group.
Contd.
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Atrial fibrillation occurred in 10% of patients at some
time during their follow-up. There were no
differences between treatment groups.
For the ischemic patients, the only significant
differences were for strokes; warfarin was better than
either aspirin or clopidogrel.
For the nonischemic patients, the only significant
finding was major hemorrhage; clopidogrel patients
had fewer major hemorrhages than warfarin patients.
Contd.
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Figure 2. A, Plot of the proportion of patients experiencing the primary composite end point of death, nonfatal MI,
or stroke during the course of the WATCH trial (warfarin vs aspirin, P0.77; warfarin vs clopidogrel, P0.39; aspirin vs
clopidogrel, P0.59). B, Plot of the proportion of patients who died during the course of the WATCH trial (warfarin vs
aspirin, P0.75; warfarin vs clopidogrel, P0.58; aspirin vs clopidogrel, P0.80).
Contd.
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DISCUSSION
WATCH trial is the largest randomized trial to date
examining antithrombotic therapies in patients with
chronic heart failure.
Result suggest that for the primary composite end point
and allcause mortality, major differences between
anticoagulation with warfarin and antiplatelet therapy
with either aspirin or clopidogrel are unlikely.
These results do not support the hypotheses that warfarin
is superior to aspirin in preventing major cardiovascular
outcomes.
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There is no support from the secondary analyses that
clopidogrel is superior to aspirin. Nonfatal strokes and all strokes were less frequent in
the warfarin arm than in the groups assigned to either
antiplatelet agent.
This findings are consistent with many physicians
belief that anticoagulation may prevent stroke in
patients with chronic systolic heart failure.
Compared with aspirin patients, the warfarin group
experienced a 26% relative reduction in the
proportion of patients hospitalized for heart failure.
Contd.
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Contd.
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However, that when an analysis of the time to first
hospitalization or death was conducted, the
differences disappeared.
Warfarin treatment in this trial was associated with
more frequent bleeding episodes compared with
clopidogrel.
A nonsignificant excess of bleeding compared with
aspirin.
Warfarin was related to a lower incidence of stroke
compared with the other 2 drugs.
Contd.
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But when central nervous system bleeding and
stroke were combined, these differences
disappeared.
The elevated risks for bleeding (major, minor
and central nervous system) versus the lower
risk for stroke must be considered when
warfarin is begun.
Contd.
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CONCLUSION
The primary outcome measure and the mortality
data do not support the primary hypotheses that
warfarin is superior to aspirin and that
clopidogrel is superior to aspirin in chronic Heart
failure patients.
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