Status:
Ongoing. We started recruitment in North America in October of 2002, and expanded to Europe in October 2004. Argentina has also been added. As of November 2009, 2205 patients have been randomized. Total of 2250 patients with 1-6 years of follow-up are required. Enrollment ends January 2010, but follow-up ends January 2011.
Purpose:
To compare the efficacies of warfarin and aspirin in preventing death, ischemic stroke, and intracerebral hemorrhage in patients with heart failure.
Location(s):
North America
Europe and Argentina
Year Started:
2002
Design:
Two-arm, double-blind, randomized, multicenter clinical trial.
Inclusion Criteria
Patients with a cardiac ejection fraction (EF) =< 35% or a wall motion index =<1.2, as determined by echocardiography, who are taking ACE inhibitors or, if intolerant of ACE inhibitors, are taking either angiotensin II receptor blockers or hydralazine and nitrates, who have a modified Rankin scale (MRS) score =< 4, are eligible for this study.
Exclusion Criteria
Pregnant females and persons with paroxysmal atrial fibrillation, mechanical valves, endocarditis, intracardiac mobile or pedunculated thrombi, valvular vegetation, cyanotic congenital heart disease, or Eisenmenger’s syndrome, who have had cardiac surgery, angioplasty, or myocardial infarction within the previous 3 months, who have New York Heart Association (NYHA) Class IV heart failure, who have any of the following contraindications to warfarin or aspirin: active peptic ulcer disease, active bleeding diathesis, platelet count < 100,000/mm3, hematocrit < 30, International Normalized Ratio (INR) > 1.3, any clotting factor abnormality that increases the risk of bleeding, any alcohol or substance abuse, severe gait instability, cerebral hemorrhage, systemic hemorrhage within the past year, severe liver impairment (aspartate aminotransferase (AST) >3x normal or cirrhosis), any condition requiring regular use of non-steroidal anti-inflammatory agents, allergy to aspirin or warfarin, uncontrolled severe hypertension (systolic >180 mmHg or diastolic > 110 mmHg), positive stool guaiac not attributable to hemorrhoids, or plasma creatinine >3.0, who require continuing therapy with intravenous heparin or a specific antiplatelet agent, who have dementia, psychiatric, or physical problems that would compromise patient reliability, who have a comorbid illness likely to limit survival to less than five years, who are enrolled in another study, who have been hospitalized for congestive heart failure (CHF), received inotropic therapy, carotid endarterectomy, or undergone a pacemaker insertion within one month of enrollment, will be excluded from this study.
Patient Involvement:
All female participants will undergo a pregnancy test prior to enrollment. Eligible patients will be randomized to receive either aspirin 325 mg/day, or warfarin, adjusted to maintain an INR of 2.5-3.0. A double-blind algorithm utilized in the WARSS trial will be used to fabricate INR values for the aspirin patients. All participants will receive monthly phone contacts and will be examined every four months for the 3-year follow-up period.
Primary Outcome:
Death, recurrent stroke, intracerebral hemorrhage
Secondary Outcome:
To test the hypothesis of no difference in warfarin and aspirin therapies in time to the first to occur of, ischemic stroke, ICH, myocardial infarction (MI), heart failure (HF) hospitalization, or death.
Results:
Over 2200 [currently 2199] of the target 3201 patients have been randomized through October 2009. No conclusive evidence identifies a preferred antithrombotic regimen for patients with HF or low LVEF, including those with prior stroke or TIA. WARCEF is the only trial directly comparing anticoagulant and antiplatelet therapies for this large population. Any of the three possible outcomes (Warfarin superior; ASA superior; neither superior) will lead to an important treatment recommendation.
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Source of Information:
Presented at the 30th International Stroke Conference [February 2005].
Presented at the 2007 International Stroke Conference [February 2007].
Presented at the 2008 International Stroke Conference [February 2008].
Presented at the 2010 International Stroke Conference [February 2010].
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