Warfarin After Anterior ST-Elevation Myocardial Infarction

This study has been completed.
Sponsor:
Information provided by:
McMaster University
ClinicalTrials.gov Identifier:
NCT00662467
First received: April 8, 2008
Last updated: April 18, 2008
Last verified: April 2008
  Purpose

Following severe heart attacks involving the front wall of the heart (anterior myocardial infarction), patients are at risk of developing blood clots in the main pumping chamber that can cause a stroke. In the past, studies have shown that a blood thinner (warfarin) can decrease the risk of stroke and clot formation if administered to patients after an anterior myocardial infarction.

However, in today's current practice, certain heart attack patients are commonly treated with two blood-thinning medications (aspirin and clopidogrel) to prevent recurrent heart attacks.

Thus, a clinical problem is created as physicians are not clear how to treat patients after an anterior myocardial infarction who are at risk of a clot but require aspirin and clopidogrel to keep their blood vessels open. Adding warfarin to the combination of aspirin and clopidogrel will possibly decrease the risk of stroke but increase the risk of bleeding. Currently, there is no good evidence to help guide physicians. As demonstrated by a survey done at the Hamilton Health Sciences, there is a fifty/fifty split between physicians who use dual (aspirin and clopidogrel) versus triple (aspirin, clopidogrel, and warfarin) therapy in the treatment of similar patients as described above.

The purpose of this study is to address the bleeding and stroke complications in patients after a severe anterior myocardial infarction. Half of the eligible patients will receive dual therapy and half will receive triple therapy. We will compare the incidence of stroke, blood clots, and bleeding complications between the two groups at 3 months.


Condition Intervention
Myocardial Infarction
Drug: aspirin + clopidogrel
Drug: aspirin + clopidogrel + warfarin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Warfarin After Anterior ST-Elevation Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Combined death, MI, embolic event (TIA, stroke, non-cns emboli), Major Bleeding, and LVT (as determined by echocardiography) at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Individual endpoints of LVT at discharge and at 3 months (determined by echocardiography), death, MI, stroke, TIA, non-CNS emboli, and minor bleeding [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: November 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
aspirin and clopidogrel
Drug: aspirin + clopidogrel
Dual therapy
Experimental: 2
aspirin, clopidogrel, and warfarin
Drug: aspirin + clopidogrel + warfarin
Triple therapy

Detailed Description:

Rationale:

Left ventricular mural thrombus (LVT) remains a common complication after anterior ST-elevation myocardial infarction (STEMI) with a reported incidence ranging from 12- 17%. Previous studies from the pre-thrombolytic era have shown that warfarin therapy significantly reduces the incidence of LVT and embolic events in patients post anterior STEMI. However, the risk/benefit ratio of warfarin therapy in the setting of early revascularization and dual antiplatelet therapy with aspirin and clopidogrel remains unknown.

Purpose:

To compare the incidence of death, MI, stroke, embolic events, LVT, and bleeding complications at 3 months in patients with an anterior STEMI and ejection fraction less than 40% treated with ASA and clopidogrel alone versus those treated with aspirin, clopidogrel, and warfarin (triple therapy group).

Sample Size:

This is a pilot project to help establish the feasibility of conducting a full scale externally funded study. As such sample size calculations are not applicable. The primary aim of the study is to determine the safety and feasibility of conducting a large-scale trial, and this pilot project in not expected to reveal a statistically significant difference between the 2 groups.

Design/Methodology:

All patients will be randomized to either aspirin and clopidogrel alone or to triple therapy with aspirin, clopidogrel and warfarin. The randomization process will be centralized and computer generated. Patients with a clear indication for oral anticoagulation such as atrial fibrillation, LV thrombus, mechanical heart valve, or DVT/PE will not undergo randomization but will be followed as part of a registry of patients on triple therapy. All patients will remain on the allocated therapy for 3 months at which time outcomes will be determined.

Study interventions:

Patients will be treated with either ASA and clopidogrel alone (dual therapy) or with aspirin, clopidogrel and warfarin (triple therapy) in combination for 3 months. Patients in the triple therapy arm will be bridged with intravenous unfractionated heparin, low molecular weight heparin, or fondaparinux until their INR is therapeutic, and will be followed by the thrombosis service for the duration of the study.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Anterior STEMI
  • An ejection fraction less than 40% as per initial LV angiography or echocardiogram
  • Randomization possible within hospital admission if anticoagulated with no interruption > 24 hours
  • Patient able and willing to give informed consent to participate in this trial

Exclusion Criteria:

  • history of intracranial hemorrhage
  • history of GI bleed last 6 months
  • hemoglobin < 90 g/L
  • platelet count < 100 x 10exp9/L
  • ischemic stroke last 30 days
  • intracranial tumor or aneurysm
  • significant pericardial effusion
  • severe renal failure (creatinine > 250 mmol/L).
  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: NCT00662467

Locations
Canada, Ontario
Hamilton Health Sciences-Hamilton General Hopsital
Hamilton, Ontario, Canada, L8L 2X2
Sponsors and Collaborators
Hamilton Health Sciences Corporation
Investigators
Principal Investigator: Jon-David R Schwalm, MD, FRCPC McMaster University
Principal Investigator: Mayraj Ahmad, MD, FRCPC McMaster University
  More Information

Publications:
Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation. 2004 Aug 31;110(9):e82-292. No abstract available. Erratum in: Circulation. 2005 Apr 19;111(15):2013-4.

Responsible Party: Dr. J-D Schwalm, McMaster University
ClinicalTrials.gov Identifier: NCT00662467     History of Changes
Other Study ID Numbers: 06-281
Study First Received: April 8, 2008
Last Updated: April 18, 2008
Health Authority: Canada: Ethics Review Committee

Keywords provided by McMaster University:
Myocardial Infarction
Hemorrhage
Thromboembolism
Clopidogrel
Aspirin
Warfarin

Additional relevant MeSH terms:
Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Aspirin
Ticlopidine
Clopidogrel
Warfarin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014