Warfarin and Antiplatelet Vascular Evaluation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00125671
Recruitment Status : Unknown
Verified September 2009 by Warfarin and Antiplatelet Vascular Evaluation.
Recruitment status was:  Active, not recruiting
First Posted : August 1, 2005
Last Update Posted : September 29, 2009
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Ontario
Information provided by:
Warfarin and Antiplatelet Vascular Evaluation

Brief Summary:
The purpose of this study is to evaluate whether the addition of warfarin (a blood-thinning medication) to an antiplatelet therapy like aspirin is better than antiplatelet therapy alone (i.e. usual treatment) for the prevention of leg surgery, heart attacks, stroke and death in people with peripheral vascular disease.

Condition or disease Intervention/treatment Phase
Peripheral Vascular Diseases Cardiovascular Diseases Drug: Warfarin Phase 3

Detailed Description:

Atherosclerosis is the underlying cause of peripheral vascular disease (PVD) of the lower extremities, and leads to intermittent claudication, leg ulceration and gangrene. More importantly, symptomatic PVD is an ominous sign that widespread atherosclerosis is present and patients with this condition suffer a threefold increase in myocardial infarction (MI), stroke, and CV death. These CV events are a consequence of rupture of an atherosclerotic plaque, which leads to platelet activation and thrombin generation, thrombus formation and occlusion of a critical blood vessel. Antiplatelet therapy has been clearly demonstrated to reduce major CV events. It is also reasonable to expect that this process may be further attenuated by the addition of an anti-thrombin agent (such as warfarin) in combination with antiplatelet agents.

WAVE is a large, international, multicentre, randomized clinical trial in high-risk PVD patients to evaluate the additional benefit of moderate intensity warfarin (target INR of 2.4-3.0) to antiplatelet therapy compared to antiplatelet therapy alone in reducing serious cardiovascular events.

There are currently 80 active centres following participants in Canada, Poland, Australia, Hungary, China, Ukraine, and the Netherlands. Following randomization to one of the two treatment groups, participants will require clinic or phone follow-up visits every 3 months for 2.5 or 3.5 years. For participants on warfarin, INRs will be measured monthly or more frequently if required. For participants who stop warfarin therapy prematurely, every attempt will be made to have them restart it

Study Type : Interventional  (Clinical Trial)
Enrollment : 2400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase III Randomized Trial of Warfarin Plus Antiplatelet Therapy Versus Antiplatelet Therapy Alone in Patients With Peripheral Vascular Disease
Study Start Date : January 2000
Study Completion Date : April 2006

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. The composite of cardiovascular (CV) death, first occurrence of myocardial infarction (MI), or stroke
  2. The composite of CV death, first occurrence of MI, stroke, or severe ischemia requiring urgent intervention of the coronary (PTCA, CABG) or peripheral artery circulation (thrombolytic therapy, angioplasty, bypass surgery, limb amputation)

Secondary Outcome Measures :
  1. CV death, MI, stroke, amputation, revascularization of the coronary or peripheral arteries, or admission to hospital for unstable angina with electrocardiogram (ECG) changes
  2. CV death, MI, stroke, transient ischemic attack (TIA), amputation or revascularization of the coronary, carotid, or leg arteries
  3. All cause death, MI, TIA, stroke, amputation, or revascularization of the coronary or peripheral arteries

Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Intermittent claudication with objective evidence of PVD (e.g. ankle-brachial index [ABI] < 0.90)
  • Ischemic rest pain of the lower limbs
  • Ischemic non-healing ulcers or focal gangrene
  • Amputation for vascular causes
  • Previous peripheral vascular revascularization (angioplasty or bypass surgery)
  • Blue toe syndrome
  • Other significant peripheral arterial disease (e.g. carotid stenosis)
  • Vascular disease and evidence of asymptomatic peripheral arterial disease [PAD] (i.e. ABI < 0.90)

Exclusion Criteria:


  • Potential subjects will be temporarily excluded if they need to undergo:

    • vascular diagnostic (angiography) or interventional procedures (arterial bypass graft surgery or angioplasty); or
    • limb amputation for vascular insufficiency.


  • Subjects will be excluded for the following:

    • active bleeding or high risk bleeding;
    • clear indication for long-term warfarin use (i.e. atrial fibrillation);
    • previous allergy or intolerance to warfarin;
    • stroke in the last 6 months;
    • renal failure requiring dialysis;
    • known significant abdominal aortic or cerebral aneurysm;
    • peripheral arterial aneurysms (iliac or femoral) without evidence of lower limb ischemia;
    • significant liver disease (i.e. cirrhosis);
    • cancer with a life expectancy < 6 months;
    • anticipated non-adherence to warfarin;
    • excessive alcohol use;
    • pregnancy or planning to become pregnant; or
    • failure to provide informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00125671

Canada, Ontario
Population Health Research Institute, McMaster University
Hamilton, Ontario, Canada, L8L 2X2
Sponsors and Collaborators
Anand, Sonia, M.D.
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Ontario
Principal Investigator: Sonia Anand, MD PhD FRCPc Population Health Research Institute, McMaster University

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00125671     History of Changes
Other Study ID Numbers: MCT-37413
First Posted: August 1, 2005    Key Record Dates
Last Update Posted: September 29, 2009
Last Verified: September 2009

Keywords provided by Warfarin and Antiplatelet Vascular Evaluation:
Warfarin and Antiplatelet Vascular Evaluation
Peripheral vascular disease
cardiovascular events
oral anticoagulants
low ankle-brachial index
moderate intensity warfarin
International normalized ratio [INR]

Additional relevant MeSH terms:
Cardiovascular Diseases
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Arterial Occlusive Diseases