Warfarin and Antiplatelet Therapy in Chronic Heart Failure

This study has been completed.
Sponsor:
Collaborators:
Sanofi-Synthelabo
Bristol-Myers Squibb
Information provided by:
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00007683
First received: December 29, 2000
Last updated: June 14, 2011
Last verified: June 2011
  Purpose

Whether patients with chronic heart failure (CHF) should be anticoagulated is one of the oldest unresolved questions in cardiovascular therapeutics. Some authorities do not recommend anticoagulation for CHF patients in sinus rhythm, others recommend anticoagulation in patients with primary cardiomyopathy, and still others consider it more appropriate in patients with coronary artery disease (CAD). This absence of consensus reflects the lack of evidence in this area and different outlooks on the objectives of such therapy (e.g., prevention of arterial emboli or reduction in vascular events).


Condition Intervention Phase
Heart Failure
Drug: Warfarin titrated to an INR of 2.5-3.0
Drug: Aspirin
Drug: Clopidogrel 75
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CSP #442 - Warfarin and Antiplatelet Therapy Study in Patients With Congestive Heart Failure (WATCH)

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • acomposite of mortality, nonfatal myocardial infarction and nonfatal stroke [ Time Frame: 30 months intake; 12-42 months follow-up ] [ Designated as safety issue: No ]
    The primary safety end point was major bleeding episodes, defined as bleeding episodes leading to death or disability (including loss of neurological or special senses function), requiring surgical intervention, or associated with an acute decline of hemoglobin 2gm/dl or transfusion of >1 U packed red cells or whole blood.


Estimated Enrollment: 1587
Study Start Date: October 1998
Study Completion Date: December 2004
Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Warfarin Titrated to an INR of 2.5-3.0
Drug: Warfarin titrated to an INR of 2.5-3.0
anticoagulation (administered without blinding) titrated to a target INR of 2.5 to 3.0, monitored by measurements at 6 week intervals after initial titration and stabilization.
Active Comparator: 2
Aspirin 182 mg
Drug: Aspirin
an antiplatelet agent whose mechanism is inhibition of thromboxane, a platelet activator) administered in a double blind manner.
Active Comparator: 3
Clopidogrel 75 mg
Drug: Clopidogrel 75
(an antiplatelet agent whose mechanism is ADP inhibition) administered in a double blind manner)

Detailed Description:

Primary Hypothesis: The hypothesis to be tested is whether aspirin, warfarin, and clopidogrel are equally effective in the treatment of patients with symptomatic CHF and reduced ejection fraction.

Secondary Hypothesis: If one therapy proves to be superior with regard to outcomes, what is the cost of this benefit? Can subsets of patients be identified who benefit more from a specific approach to antithrombotic therapy?

Intervention: The three treatment regimens are:

  1. Open-label Warfarin titrated to an INR of 2.5-3.0;
  2. Double blind aspirin 162 mg once daily;
  3. Double blind clopidogrel 75 mg once daily.

Primary Outcomes: Any death (all causes), non-fatal stroke, non-fatal MI.

Study Abstract: Whether patients with chronic heart failure (CHF) should be anticoagulated is one of the oldest unresolved questions in cardiovascular therapeutics. Some authorities do not recommend anticoagulation for CHF patients in sinus rhythm, others recommend anticoagulation in patients with primary cardiomyopathy, and still others consider it more appropriate in patients with coronary artery disease (CAD). This absence of consensus reflects the lack of evidence in this area and different outlooks on the objectives of such therapy (e.g., prevention of arterial emboli or reduction in vascular events).

The original target sample size was 4,500 over a 3 year enrollment period with a 2 year follow-up. This sample size yielded 90% power to detect a relative difference of 20% between treatment groups. The sample size was later amended to 1,500 over a 30 month enrollment period with a 12 month follow-up. The reduced sample size yielded 85% to detect a between treatment difference of 30%. This change became effective in March 2002.

This clinical trial enrolled 1,587 patients in 142 medical centers; VA and non-VA centers in the U.S., and medical centers in the United Kingdom and Canada. Patients were randomly and equally allocated to the 3 treatments: warfarin (administered open-label), aspirin and clopidogrel (the latter two administered double-blind). The study was conducted over a 3.5 year period, with a 2.5 year enrollment phase.

Patients with NYHA class II, III, or IV and left ventricular ejection fractions less than or equal to 35% on an ACE inhibitor (unless not tolerated) and a diuretic were entered. The primary end point is the composite of death from any cause, non-fatal MI, and non-fatal stroke. All-cause mortality is the secondary end point.

The WATCH design paper has been published in the Journal of Cardiac Failure. Preliminary results were presented at the meeting of the American College of Cardiology in New Orleans on March 9, 2004. There were no significant differences between the treatment groups for the primary endpoints. The paper with final results is being prepared.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion Criteria:

  • Patients with NYHA class II, III, or IV and left ventricular ejection fractions less than or equal to 35%, on an ACE inhibitor (unless not tolerated) and on a diuretic.

Exclusion Criteria:

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00007683

  Show 134 Study Locations
Sponsors and Collaborators
Sanofi-Synthelabo
Bristol-Myers Squibb
Investigators
Study Chair: Barry M. Massie, MD VA Medical Center, San Francisco
  More Information

Publications:
Responsible Party: Massie, Barry - Study Chair, Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00007683     History of Changes
Other Study ID Numbers: 442
Study First Received: December 29, 2000
Last Updated: June 14, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
aspirin
clopidogrel
embolic events
Left ventricular ejection fraction less than or eq
NYHA Class II, III or IV CHF
symptomatic CHF
warfarin

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Aspirin
Clopidogrel
Warfarin
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anticoagulants
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists

ClinicalTrials.gov processed this record on October 20, 2014