Myocardial Infarction Triage and Intervention Project (MITI)
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Infarction; Myocardial Ischemia
MeSH terms: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Coronary Disease; Myocardial Ischemia; Infarction; Ischemia
Study type: Interventional
Phase: Phase 3

Summary: 
      To determine the practicality, benefit, and safety of paramedic administration of
      thrombolytic therapy for acute myocardial infarction. The feasibility of paramedics correctly
      identifying candidates for thrombolytic therapy following myocardial infarction was assessed
      in Phase I. In Phase II, pre-hospital thrombolytic therapy was compared with in-hospital
      thrombolytic therapy.
    

Detailed description: 
      BACKGROUND:

      In the past, patients with acute myocardial infarction were treated by putting them to bed.
      It was felt that once the symptoms and electrocardiographic signs of acute myocardial
      infarction had occurred, the process was complete and that the heart and patient at rest
      would allow the illness to run its course and the heart to heal. The focus of treatment in
      the Coronary Intensive Care Unit was to prevent complications of acute myocardial infarction,
      primarily arrhythmias leading to cardiac arrest and the treatment of cardiac arrest itself.
      Acute phase morbidity and mortality related to loss of myocardium through infarction has not
      changed. Post-discharge mortality and morbidity is, in large part, related to the occurrence
      of congestive heart failure, secondary to loss of myocardium to infarction. Efforts to
      preserve myocardium through pharmacologic intervention to limit demand, have not resulted in
      significant benefit. It is now recognized that the infarction is not complete on
      presentation, that it occurs as a wavefront over a period of four to six hours, and that in
      80 to 90 percent of patients, infarction is due to thrombus in the infarct-related artery.
      Therefore, reperfusion of the jeopardized myocardium during this window of four to six hours
      could result in salvage of myocardium with resultant decrease in acute mortality as well as
      acute and chronic morbidity and mortality from myocardial failure.

      The international streptokinase trials have established the feasibility of intravenous
      coronary thrombolysis with streptokinase and demonstrated a decrease in acute morality
      ranging from 18 percent to 50 percent, depending upon the interval between the onset of chest
      pain and the initiation of thrombolytic therapy. Furthermore, preservation of ventricular
      function, as reflected in ejection fraction, is greater with early administration.

      The TIMI trial of tissue plasminogen activator (TPA), which is more clot-specific than
      streptokinase, has substantiated the effectiveness. The initiation of thrombolytic therapy
      with TPA as early as possible after the onset of symptoms offers an advantage, therefore, in
      terms of both a reduction in acute mortality and salvage of ischemic myocardium.

      Although thrombolysis is being performed at community hospitals or enroute to hospitals by
      specially trained teams using helicopter transport, only one major study has been reported
      which has systematically evaluated the benefit of early on-the-scene thrombolysis. This study
      documented significant benefit in terms of salvage of myocardium over those patients in whom
      thrombolytic therapy was initiated after arrival in the hospital, as a direct function of
      time. This program used physicians in the ambulance to evaluate indications for and
      contraindications to thrombolytic therapy in the field. The proposed study would evaluate the
      ability of paramedics, under physician remote control, to accurately evaluate patients in the
      field in terms of indications and contra-indications to thrombolytic therapy, and to assess
      the possible benefit in terms of salvage of myocardium in those patients being transported to
      the hospital by paramedic squads as opposed to those arriving by ordinary means.

      DESIGN NARRATIVE:

      In Phase I, the paramedics took electrocardiograms of patients who met the definition of
      cases and administered an abbreviated questionnaire. This phase tested the feasibility of
      paramedics making a diagnosis of acute myocardial infarction on the basis of clinical history
      and with the support of computerized electrocardiogram, coming to an appropriate decision to
      initiate thrombolytic therapy on the basis of the field database, and recognizing appropriate
      contraindications to thrombolytic therapy with and without remote physician supervision. An
      analysis was conducted of the pre-hospital selection of patients for thrombolytic therapy.

      Criteria for approval to move to Phase II included correct identification of appropriate
      cases for treatment 75 percent of the time, less than five percent inappropriate cases or
      with contraindications for thrombolytic therapy, and no more than one percent of the selected
      cases found to have initial life-threatening hemorrhagic conditions.

      Beginning in November 1988, Phase II compared initiation of thrombolysis with tissue
      plasminogen activator (TPA) in the field to initiation in the hospital. During Phase II,
      which lasted for 24 months, one half of the patients meeting the case definition received
      paramedic administration of intravenous thrombolytic therapy and one half received the same
      pre-hospital diagnostic steps but treatment administered after transport to the hospital. The
      360 patients with symptoms for six hours or less, no risk factors for serious bleeding, and
      ST-segment elevation, were selected by paramedics and a remote physician for inclusion in the
      trial. They were allocated to aspirin and alteplase treatment initiated before or after
      hospital arrival. Intravenous sodium heparin was administered to both groups in the hospital.
      Nineteen hospitals in the Seattle and King County areas participated. The primary endpoint
      was a ranked composite score (combining death, stroke, serious bleeding, and infarct size).
      The relation between time to treatment and outcome (composite score, infarct size, ejection
      fraction, and mortality) was also assessed.

      In Phase II, a myocardial infarction registry was established to include all patients
      hospitalized in the area with a discharge diagnosis of acute myocardial infarction. The
      registry placed the trial findings in a community-based perspective and aided in the
      interpretation of trial findings by assessing the proportion of cases seeking paramedic care
      and determining the characteristics of these patients in contrast to those arriving at the
      hospital by other means. The records of all patients admitted directly to coronary care units
      in Seattle and King County were surveyed. Study personnel examined differences, if any,
      between paramedic and other transport groups regarding clinical history, treatment,
      complications, and hospital discharge rates. Of the cases in the registry, 300 who arrived at
      the hospital by means other than paramedic transport were compared to the
      paramedic-transported cases with respect to the incidence of new Q-wave infarction on the
      first and last electrocardiogram, an interview to determine onset, severity, and duration of
      symptoms, and reasons for choosing one type of care over the other during the emergency
      situation.
    

Intervention name(s): tissue plasminogen activator
Intervention type(s): Drug
Intervention MeSH terms: Plasminogen; Tissue Plasminogen Activator
Primary purpose: Treatment