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Warfarin After Anterior ST-Elevation Myocardial Infarction

Not Applicable
Completed
Conditions
Myocardial Infarction
Interventions
Registration Number
NCT00662467
Lead Sponsor
Hamilton Health Sciences Corporation
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1aspirin + clopidogrelaspirin and clopidogrel
2aspirin + clopidogrel + warfarinaspirin, clopidogrel, and warfarin
Primary Outcome Measures
NameTimeMethod
Combined death, MI, embolic event (TIA, stroke, non-cns emboli), Major Bleeding, and LVT (as determined by echocardiography) at 3 months3 months
Secondary Outcome Measures
NameTimeMethod
Individual endpoints of LVT at discharge and at 3 months (determined by echocardiography), death, MI, stroke, TIA, non-CNS emboli, and minor bleeding3 months

Trial Locations

Locations (1)

Hamilton Health Sciences-Hamilton General Hopsital

🇨🇦

Hamilton, Ontario, Canada

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