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

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

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Stroke; Ischemic Heart Disease; Heart Disease
• Intervention / Treatment: Drug: aspirin; Drug: Warfarin

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.

• Study Type: Interventional
• Enrollment (Actual): 2305
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Lethbridge, Alberta, Canada
      • Center for Neurologic Research
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • St. Boniface General Hospital
  • New Brunswick
    • Saint John, New Brunswick, Canada
      • Saint John Regional Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • QE II Health Sciences Centre
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada
      • Ottawa Heart Institute
    • Rexdale, Ontario, Canada
      • Etobicoke Cardiac Research Centre
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Montreal Heart Institute
    • Montreal, Quebec, Canada
      • Montreal General Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States
      • University of Arizona Health Sciences Center
    • Tucson, Arizona, United States
      • Southern Arizona Veterans Affairs Medical Center
  • California
    • Santa Clara, California, United States
      • Santa Clara Medical Center
    • West Los Angeles, California, United States
      • West Los Angeles Veterans Affairs Medical Center
  • Colorado
    • Denver, Colorado, United States
      • Denver Health Medical Center
    • Denver, Colorado, United States
      • Denver Veterans Affairs Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University
  • Florida
    • Jacksonville, Florida, United States
      • Mayo Clinic Transplant Center
    • Melbourne, Florida, United States
      • Melbourne Internal Medicine Associates
    • Miami, Florida, United States
      • Jackson Memorial Hospital/U. of Miami
    • Miami, Florida, United States
      • Mercy Research Institute
    • Tamarac, Florida, United States
      • Cardiovascular Consultants of South Florida
  • Georgia
    • Atlanta, Georgia, United States
      • Morehouse School of Medicine
    • Gainesville, Georgia, United States
      • Northeast Georgia Heart Center
  • Illinois
    • Chicago, Illinois, United States
      • University of Illinois at Chicago
    • Peoria, Illinois, United States
      • Methodist Heart, Lung and Vascular Institute
  • Kentucky
    • Lexington, Kentucky, United States
      • University of Kentucky
    • Louisville, Kentucky, United States
      • University of Louisville
    • Louisville, Kentucky, United States
      • Louisville Veterans Affairs Medical Center
  • Louisiana
    • Metairie, Louisiana, United States
      • Gulf Regional Research, LLC
    • Shreveport, Louisiana, United States
      • LSU Health Sciences Center
  • Massachusetts
    • Burlington, Massachusetts, United States
      • Lahey Clinic
  • Michigan
    • Detroit, Michigan, United States
      • Veterans Affairs Medical Center
    • Muskegon, Michigan, United States
      • Mercy Health Partners
  • Nevada
    • Reno, Nevada, United States
      • Reno Veterans Affairs Medical Center
  • New Hampshire
    • Concord, New Hampshire, United States
      • Concord Hospital
  • New Jersey
    • New Brunswick, New Jersey, United States
      • UMDNJ - New Brunswick
    • Newark, New Jersey, United States
      • University of Medicine and Dentistry of New Jersey
  • New York
    • Albany, New York, United States
      • Albany Medical College
    • Buffalo, New York, United States
      • Buffalo General Hospital
    • Buffalo, New York, United States
      • Kaleida Health Millard Fillmore Hospital
    • Cedarhurst, New York, United States
      • Five Towns Neuroscience Research
    • New Hyde Park, New York, United States
      • Long Island Jewish Medical Center
    • New York, New York, United States
      • Columbia University Medical Center
    • New York, New York, United States
      • Mount Sinai Medical Center
    • New York, New York, United States, 10032
      • Columbia University, New York Presbyterian Hospital PH 3-342
    • Northport, New York, United States
      • Northport Veterans Affairs Medical Center
    • Rochester, New York, United States
      • University of Rochester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States
      • MetroHealth Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Oklahoma City Veterans Affairs Medical Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States
      • Lehigh Valley Hospital
    • Beaver, Pennsylvania, United States
      • Tri-State Medical Group Cardiology
    • Leetsdale, Pennsylvania, United States
      • Sewickley Valley Medical Group, Cardiology
    • Philadelphia, Pennsylvania, United States
      • Hospital of The University of Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States
      • Penn Presbyterian Medical Center
  • South Dakota
    • Fort Meade, South Dakota, United States
      • Black Hills Health Care System
  • Texas
    • Ft. Sam Houston, Texas, United States
      • Brooke Army Medical Center MCHE - MDC Cardiology Service
    • Houston, Texas, United States
      • Michael E. DeBakey Veterans Affairs Medical Center-MEDVAMC
  • Virginia
    • Salem, Virginia, United States
      • Salem Vamc
  • West Virginia
    • Huntington, West Virginia, United States
      • Huntington Veterans Affairs Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States
      • William S. Middleton Memorial Veterans Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Cardiac EF <=35% by radionuclide ventriculography, left ventriculography or quantitive echocardiographic measurement or an echocardiographic Wall Motion Index of <=1.2, within three months of enrollment. The patient's clinical cardiac state at enrollment should be similar to their state at the time of the qualifying echocardiogram. The qualifying left ventricular function measurement must be obtained at least three months after an MI, coronary bypass grafting, PTCA, and at least one month after pacemaker insertion. Patients scheduled for mitral valve repair should have qualifying echo after surgery.
• Modified Rankin score <=4.
• Patient must be taking ACE inhibitors. If intolerant of ACE inhibitor, patient must be on angiotensin II receptor blockers or hydralazine and nitrates.
• Patient is able to follow an outpatient protocol (requiring monthly blood tests and clinic visits every four months for the duration of the study) and is available by telephone.
• Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent.
• Patients with recent stroke or TIA within twelve (12) months will be eligible to be included in the recent stroke (RS) subgroup.
• Chronic CHF patients (NYHA I * IV) admitted to the hospital can be randomized prior to discharge if the patient is stable, taking oral medications for 24 hours and ambulatory at the time of discharge. Stable New York Heart Association Class IV patients will be eligible for randomization.

Exclusion Criteria

• The presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal AF, mechanical valve, endocarditis, intracardiac mobile or pedunculated thrombus, and valvular vegetation.
• Cyanotic congenital heart disease, Eisenmenger's syndrome.
• Decompensated heart failure.
• Cardiac surgery, angioplasty, or MI within the past 3 months prior to randomization.
• A contraindication to the use of either warfarin or aspirin, e.g. active peptic ulcer disease, active bleeding diathesis, platelets <100,000*, hematocrit <30, INR >1.3 (if not on warfarin), clotting factor abnormality that increases the risk of bleeding, alcohol or substance abuse, severe gait instability, cerebral hemorrhage, systemic hemorrhage within the past year, severe liver impairment (AST >3x normal*, cirrhosis), any condition requiring regular use of non-steroidal anti-inflammatory agents, allergy to aspirin or warfarin, uncontrolled severe hypertension (systolic pressure >180 mm Hg or diastolic pressure > 110 mm Hg), positive stool guaiac not attributable to hemorrhoids, creatinine >3.0*. *on most recent test done within 30 days prior to randomization
• Patient needs continuing therapy with intravenous heparin or low molecular weight heparin or a specific antiplatelet agent.
• Dementia or psychiatric or physical problem that prevents the patient from following an outpatient program reliably.
• Comorbid conditions that may limit survival to less than five years.
• Pregnancy, or female of childbearing potential who is not sterilized or is not using a medically accepted form of contraception* (see procedure manual). *A pregnancy test is required for all women of childbearing age.
• Enrollment in another study that would conflict with WARCEF.
• Hospitalization for new diagnosis of onset CHF within the past one month or carotid endarterectomy or pacemaker insertion within the past one month prior to randomization .
• Person under 18 years of age.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: aspirin; Aspirin: 325 mg per day	Drug: aspirin; 325 mg per day
Active Comparator: warfarin; Warfarin: International Normalized Ratio (INR) 2.5-3.0; target INR 2.75	Drug: Warfarin; INR 2.5-3.0; target INR 2.75

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death	The time, in years, from randomization to the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.	The time, in years, from date of randomization to the date of the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Rate Per 100 Patient-years for Ischemic Stroke	Time, in years, from date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years
Event Rate Per 100 Patient-years for Intracerebral Hemorrhage	Time, in years, from date of randomization to date of intracerebral hemorrhage component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years
Event Rate Per 100 Patient-years for Death	Time, in years, from date of randomization to date of death component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of death component of primary composite outcome, up to 6 years
Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome	Time, in years, from date of randomization to date of myocardial infarction, up to 6 years. Includes only myocardial infarctions that occurred during follow-up, before any heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with myocardial infarction)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years
Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.	Time, in years, from date of randomization to date of heart failure hospitalization, up to 6 years. Includes hospitalizations for heart failure during follow-up that were not preceded by myocardial infarction. Event rate per 100 patient years = 100*(number of subjects with heart failure hospitalization)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years
Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome	Ischemic stroke component of secondary composite endpoint. Includes only ischemic strokes that were not preceded by a myocardial infarction or heart failure hospitalization. The number of ischemic strokes that are components of the secondary outcome does not therefore match the number of ischemic strokes that are components of the primary outcome. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.	From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years
Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome	Time, in years, from date of randomization to date of intracerebral hemorrhage component of secondary composite outcome. Includes only intracerebral hemorrhages not preceded by myocardial infarction or heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years
Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome	Time, in years, from randomization to death component of secondary composite outcome. This measure counts only deaths that were not preceded by heart failure hospitalization, myocardial infarction, ischemic stroke, or intracerebral hemorrhage. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of death component of secondary composite outcome, up to 6 years
Rate Per 100 Patient Years of Major Hemorrhage	Rate/100 patient-years of major hemorrhage. Includes all major hemorrhages in any patient. Major hemorrhage was defined as intracerebral, epidural, subdural, subarachnoid, spinal intramedullary, or retinal hemorrhage; any other bleeding causing a decline in the hemoglobin level of more than 2 g per deciliter in 48 hours; or bleeding requiring transfusion of 2 or more units of whole blood, hospitalization, or surgical intervention. Event rate per 100 patient years = 100*(number of major hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization until end of scheduled follow-up, up to 6 years
Rate Per 100 Patient-years of Minor Hemorrhage.	Rate per 100 patient years of minor hemorrhage. Includes all minor hemorrhages. Minor hemorrhage was defined as any non-major hemorrhage. Event rate per 100 patient years = 100*(number of minor hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.	From date of randomization until the end of scheduled follow-up, up to 6 years

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Shunichi Homma, M.D., Principal Cardiologist, Associate Chief, Division of Cardiology, and Director, Echocardiography Laboratories Professor of Medicine; Principal Investigator: Seamus Thompson, PhD, Statistical PI: Clinical Professor of Biostatistics and Neurology

Publications and helpful links

General Publications

• Lee TC, Qian M, Liu Y, Graham S, Mann DL, Nakanishi K, Teerlink JR, Lip GYH, Freudenberger RS, Sacco RL, Mohr JP, Labovitz AJ, Ponikowski P, Lok DJ, Matsumoto K, Estol C, Anker SD, Pullicino PM, Buchsbaum R, Levin B, Thompson JLP, Homma S, Di Tullio MR; WARCEF Investigators. Cognitive Decline Over Time in Patients With Systolic Heart Failure: Insights From WARCEF. JACC Heart Fail. 2019 Dec;7(12):1042-1053. doi: 10.1016/j.jchf.2019.09.003.
• Teerlink JR, Qian M, Bello NA, Freudenberger RS, Levin B, Di Tullio MR, Graham S, Mann DL, Sacco RL, Mohr JP, Lip GYH, Labovitz AJ, Lee SC, Ponikowski P, Lok DJ, Anker SD, Thompson JLP, Homma S; WARCEF Investigators. Aspirin Does Not Increase Heart Failure Events in Heart Failure Patients: From the WARCEF Trial. JACC Heart Fail. 2017 Aug;5(8):603-610. doi: 10.1016/j.jchf.2017.04.011.
• Di Tullio MR, Qian M, Thompson JL, Labovitz AJ, Mann DL, Sacco RL, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Lip GY, Levin B, Mohr JP, Buchsbaum R, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Homma S; WARCEF Investigators. Left Ventricular Ejection Fraction and Risk of Stroke and Cardiac Events in Heart Failure: Data From the Warfarin Versus Aspirin in Reduced Ejection Fraction Trial. Stroke. 2016 Aug;47(8):2031-7. doi: 10.1161/STROKEAHA.116.013679. Epub 2016 Jun 28.
• Freudenberger RS, Cheng B, Mann DL, Thompson JL, Sacco RL, Buchsbaum R, Sanford A, Pullicino PM, Levin B, Teerlink JR, Graham S, Mohr JP, Labovitz AJ, Di Tullio MR, Lip GY, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Homma S; WARCEF Investigators. The first prognostic model for stroke and death in patients with systolic heart failure. J Cardiol. 2016 Aug;68(2):100-3. doi: 10.1016/j.jjcc.2015.09.014. Epub 2015 Nov 6.
• Homma S, Thompson JL, Qian M, Ye S, Di Tullio MR, Lip GY, Mann DL, Sacco RL, Levin B, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Mohr JP, Labovitz AJ, Buchsbaum R, Estol CJ, Lok DJ, Ponikowski P, Anker SD; WARCEF Investigators. Quality of anticoagulation control in preventing adverse events in patients with heart failure in sinus rhythm: Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial substudy. Circ Heart Fail. 2015 May;8(3):504-9. doi: 10.1161/CIRCHEARTFAILURE.114.001725. Epub 2015 Apr 7.
• Shaffer JA, Thompson JL, Cheng B, Ye S, Lip GY, Mann DL, Sacco RL, Pullicino PM, Freudenberger RS, Graham S, Mohr JP, Labovitz AJ, Estol CJ, Lok DJ, Ponikowski P, Anker SD, Di Tullio MR, Homma S; WARCEF Investigators. Association of quality of life with anticoagulant control in patients with heart failure: the Warfarin and Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Int J Cardiol. 2014 Dec 15;177(2):715-7. doi: 10.1016/j.ijcard.2014.10.012. No abstract available.
• Homma S, Thompson JL, Sanford AR, Mann DL, Sacco RL, Levin B, Pullicino PM, Freudenberger RS, Teerlink JR, Graham S, Mohr JP, Massie BM, Labovitz AJ, Di Tullio MR, Gabriel AP, Lip GY, Estol CJ, Lok DJ, Ponikowski P, Anker SD; WARCEF Investigators. Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: a subgroup analysis of WARCEF, a randomized controlled trial. Circ Heart Fail. 2013 Sep 1;6(5):988-97. doi: 10.1161/CIRCHEARTFAILURE.113.000372. Epub 2013 Jul 23.
• Homma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS, Teerlink JR, Ammon SE, Graham S, Sacco RL, Mann DL, Mohr JP, Massie BM, Labovitz AJ, Anker SD, Lok DJ, Ponikowski P, Estol CJ, Lip GY, Di Tullio MR, Sanford AR, Mejia V, Gabriel AP, del Valle ML, Buchsbaum R; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012 May 17;366(20):1859-69. doi: 10.1056/NEJMoa1202299. Epub 2012 May 2.

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: July 19, 2002
• First Submitted That Met QC Criteria: July 19, 2002
• First Posted (Estimate): July 22, 2002

Study Record Updates

• Last Update Posted (Estimate): September 5, 2014
• Last Update Submitted That Met QC Criteria: August 29, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: stroke; atrial fibrillation; ischemic heart disease; myocardial infarction; anticoagulant; Warfarin; aspirin; cardiac failure; heart disease; low ejection fraction
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Infarction; Infarction; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Anticoagulants; Aspirin; Warfarin
• Other Study ID Numbers: AAAC1093; CRC (NINDS); U01NS039143-01 (U.S. NIH Grant/Contract); R01NS39154