Acute Myocardial Infarction Study of Adenosine Trial - AMISTAD I

Description:

The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo. The trial was designed to assess if adenosine as an adjunct to thrombolysis would reduce myocardial infarct size.

Hypothesis:

Adenosine as an adjunct to thrombolysis would reduce myocardial infarct size by 35%. The primary endpoint of infarct size was to be analyzed using multivariable regression modeling to adjust for covariates: MI location, time from enrollment to determination of the final infarct size, use of revascularization procedures, type of thrombolytic therapy, use of lidocaine, interaction between treatment and MI location and interaction between treatment and type of thrombolytic therapy.

Study Design

Study Design:

Patients Enrolled: 236
Mean Follow Up: 4-6 weeks after hospital discharge
Mean Patient Age: 18-79
Female: 24

Patient Populations:

Presentation within 6 h of the onset of chest pain (consistent with ischemia, lasting at least 20 min, and not relieved by sublingual nitroglycerin); ST segment elevation .0.1 mV in two contiguous leads; clinical decision made to treat with thrombolytic therapy.

Exclusions:

Age <18 years or >79 years; Women known or suspected to be pregnant; Dipyridamole treatment within the past 24 h; Systolic blood pressure <100 mm Hg; Cardiogenic shock; underlying condition in which hypotension may be poorly tolerated; history or clinical evidence of bronchospastic lung disease or prior bronchodilator therapy; second-degree or greater atrioventricular block without functional pacemaker; left bundle branch block; sustained bradycardia (<60 beats/min for >20 min); current enrollment in other investigational drug studies; patient unlikely to be available for follow-up.

Primary Endpoints:

Infarct size as determined by Tc-99 m sestamibi SPECT imaging 5-7 days after enrollment based on multivariable regression modeling to adjust for covariates.

Secondary Endpoints:

myocardial salvage index; composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke).

Drug/Procedures Used:

Patients were stratified by MI location (anterior or nonanterior as assessed by the site investigator) and then randomly assigned to adenosine given by peripheral intravenous infusion at 70 mg/kg/min for 3 h or placebo (normal saline at 70 mg/kg/min for 3 h). Study drug administration was to begin prior to initiation of thrombolytic therapy. In patients undergoing acute cardiac imaging, SPECT imaging was to be performed within 6 h after injection of Tc-99 m sestamibi (20-to 30-mCi dose), which was to be injected before thrombolytic therapy began (accelerated alteplase or streptokinase per institutional protocol). IV lidocaine was also to be given before thrombolytic therapy began, according to individual institutional protocol, to achieve and maintain therapeutic levels for >=6 h.

Principal Findings:

Infarct size was assessed in 197 (83%) patients. Infarct size was significantly reduced in adenosine treated patients (p=0.03 after adjustment for covariates of infarct size). There was a 33% relative reduction in infarct size with adenosine (13% in adenosine group vs 19.5% in placebo group, p=0.085). There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group, p=0.014) but no reduction in patients with nonanterior infarcts (11.5% for both groups, p=0.96). Patients randomized to adenosine tended to reach the composite clinical endpoint more often than those assigned to placebo (22% vs. 16%; OR 1.43; 95% CI 0.71-2.89).

Interpretation:

Use of adenosine with reperfusion therapy resulted in a significant reduction in infarct size compared with placebo patients. The reduction in infarct size may be related to the ability of adenosine to modify the cellular responses to injury and to participate in ischemic preconditioning. Despite the reduction in infarct size in the adenosine group, in-hospital clinical outcomes tended to occur more frequently in adenosine treated patients compared with placebo although the overall number of events was small. These data support the need for a large clinical outcome trial.

References:

J Am Coll Cardiol 1999;34:1711–1720.

Clinical Topics: Dyslipidemia, Noninvasive Imaging, Lipid Metabolism, Computed Tomography, Nuclear Imaging

Keywords: Thrombolytic Therapy, Myocardial Infarction, Streptokinase, Chest Pain, Tomography, Emission-Computed, Single-Photon, Lidocaine, Coronary Disease, Tissue Plasminogen Activator, Infusions, Intravenous, Ischemic Preconditioning, Nitroglycerin


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