Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial "WARCEF"

Completed

Phase 3 Results

Trial Description

The purpose of this study is to determine which of two treatments, Warfarin or aspirin, is better for preventing death and stroke in patients with poor heart function.
We are now transitioning into the sub-analysis part of the WARCEF patient data.
The study has recently completed data analysis for its Primary Aim. All randomized patients have completed their follow up. All study related procedure as per the protocol has been completed. We are now in the extension phase of the study to obtain more patient data to address further aims of the study. No new procedures are performed and data already in place at the sites will be collected (EKG and echocardiograms).
The aims for this study extension are:
- To assess progression of cardiac dysfunction over time among heart failure patients
- To correlate prognosis with cardiac dysfunction

Detailed Description

Warfarin has proven effective in patients with ischemic heart disease, especially in the reduction of stroke, death and re-infarction following myocardial infarction, and in the reduction of stroke in atrial fibrillation. Warfarin is the most promising unstudied intervention in patients with cardiac failure. This randomized, double-blind, multi-center study will define optimal antithrombotic therapy for patients with cardiac (heart) failure and patients with low ejection fraction (EF). EF is the proportion of left ventricular volume emptied during systole. It reliably measures left ventricular systolic function.
With the rapidly increasing numbers of elderly patients with heart failure, this study has important public health implications. The study will determine which of two commonly used treatments Warfarin, an anticoagulant, or aspirin, a drug which affects platelet function is better for preventing death and stroke in patients with low ejection fraction.

Conditions

Interventions

  • Aspirin (stroke prevention) Drug
    Intervention Desc: Antiplatelet agent; inhibits thromboxane A2
  • Warfarin (CoumadinĀ®)Drug
    Intervention Desc: INR 2.5-3.0; target INR 2.75
    ARM 1: Kind: Experimental
    Label: 2
    Description: warfarin
    ARM 2: Kind: Experimental
    Label: warfarin
    Description: Warfarin: International Normalized Ratio (INR) 2.5-3.0; target INR 2.75
  • Aspirin Drug
    Other Names: Acetylsalicylic Acid
    Intervention Desc: 325 mg per day
    ARM 1: Kind: Experimental
    Label: 1
    Description: aspirin
    ARM 2: Kind: Experimental
    Label: aspirin
    Description: Aspirin: 325 mg per day

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Investigator)
  • Purpose: Prevention
  • Intervention: Parallel Assignment

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.

Outcomes

Type Measure Time Frame Safety Issue
Primary Death, recurrent stroke, intracerebral hemorrhage
Secondary 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.
Primary Comparison of aspirin and warfarin to determine if either is superior for preventing the combined endpoint of all-cause mortality and stroke in patients with left ventricular ejection fraction <35%. 1 to 6 years Yes
Primary Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years Yes
Secondary Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death. From randomization to the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. Yes

Sponsors