Warfarin After Anterior ST-Elevation Myocardial Infarction
Condition: Myocardial Infarction
MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction
Study type: Interventional

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.
    

Intervention name(s): aspirin + clopidogrel; aspirin + clopidogrel + warfarin
Intervention type(s): Drug; Drug
Intervention description(s): Dual therapy; Triple therapy
Intervention MeSH terms: Aspirin; Warfarin; Clopidogrel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myocardial Infarction; Hemorrhage; Thromboembolism; Clopidogrel; Aspirin; Warfarin