the warfarin and antiplatelet therapy in chronic heart failure (watch) trial,nivcd

7/27/2019 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

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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.

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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.

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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).

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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.

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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.

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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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the warfarin and antiplatelet therapy in chronic heart failure (watch) trial,nivcd

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