Coronary Heart Disease/Myocardial Infarction: Intravenous Fluosol in the Treatment of Acute Myocardial Infarction: Results of the Thrombolysis and Angioplasty in Myocardial Infarction 9 Trial - TAMI-9

Description:

The TAMI-9 trial was a prospective, multicenter, randomized, open-labeled, placebo-controlled trial, designed to determine the safety and potential efficacy of an intravenous perfluorochemical emulsion (Fluosol) as an adjunct reperfusion therapy aimed at preventing reperfusion injury for patients with acute myocardial infarction.

Hypothesis:

In patients with acute myocardial infarction, global ejection fraction, regional wall motion analysis, infarct size and a composite clinical outcome measure would be improved with the use of Fluosol as an adjunct reperfusion therapy.

Study Design

Study Design:

Patients Enrolled: 430

Patient Populations:

Symptoms consistent with an acute MI of <6 hours duration unresponsive to sublingual nitroglycerin; age >18 and <75 years of age; ST-segment elevation of at least 0.1 mV in at least two of six precordial leads, two of three inferior leads, or in both leads I and aVL; and ability and willingness to give informed consent to participate in this study.

Exclusions:

Treatment with Fluosol within the previous 6 months, ongoing renal dialysis, clinically significant liver disease, chronic obstructive pulmonary disease, other serious advanced illnesses likely to limit life expectancy, prolonged cardiopulmonary resuscitation (>10 minutes) within the previous 2 weeks, other standard contraindications to thrombolytic therapy, previous coronary artery bypass graft surgery, previous Q-wave infarction, and cardiogenic shock.

Primary Endpoints:

Global ejection fraction, regional wall motion analysis, infarct size as measured by tomographic thallium imaging, and a composite clinical outcome measure (death from any cause, stroke, nonfatal reinfarction, emergency revascularization, development of new heart failure or pulmonary edema, or significant recurrent ischemia).

Secondary Endpoints:

Arrhythmias, sustained hypotension, Killip class II or III, acute septal rupture, acute mitral regurgitation, pericarditis, coma, renal failure, respiratory failure, bleeding.

Drug/Procedures Used:

All patients were initially treated with 324 mg of chewable aspirin, intravenous heparin, and 100 mg of intravenous tissue-type plasminogen activator (tPA) over 3 hours. In addition, patients received intravenous atenolol unless they had atrioventricular block, systolic blood pressure <100 mm Hg, heart rate <60 beats per minute, bibasilar rales, or a significant history of bronchospasm. Intravenous morphine, nitroglycerin, and atropine also were used at the discretion of the investigator. After the initiation of the above therapy, patients were randomized to receive intravenous Fluosol (n=217) or placebo (n=213). Intravenous Fluosol was administered at the rate of 1 mL/min for the first 5 minutes, 5 mL/min for the next 5 minutes, and 20 mL/min until a total of 15 mL/kg had been administered. The rate was reduced in the presence of any sign of pulmonary congestion or edema; 77% of patients received the full dose. All patients continued to receive intravenous heparin at a rate of 1000 U/h to maintain the partial thromboplastin time at 1.5 to 2 times the control value. An effort was made to perform cardiac catheterization, including coronary angiography and left ventriculography and tomographic thallium imaging 5 to 14 days after thrombolytic therapy.

Principal Findings:

There were no substantial differences in baseline characteristics. No significant difference in the mean global LV ejection fraction was seen between the two groups in the entire population (52% in the placebo group versus 51% in the Fluosol group, p=NS) and in the subset of patients with anterior myocardial infarction (47% in the placebo group versus 46% in the Fluosol group, p=NS). Infarct zone regional wall motion for all patients (-2.5 vs -2.6 SD/chord for the placebo and Fluosol group, respectively) and for those with anterior MI (-2.5 vs -2.7 SD/chord for the placebo and Fluosol group, respectively) showed no significant difference between groups. Thallium infarct size was measured as the percentage of LV damage. No significant difference was noted after Fluosol compared with placebo for the entire population (mean 14.2 vs 15.1 percent of left ventricle, respectively). No differences were observed in the proportion of patients with patent infarct-related arteries or in the TIMI grades at the time of the first cardiac catheterization (TIMI grade 3 69% in the placebo group vs 68% in the Fluosol group). Although the primary composite end point was not significantly different between the two groups, a definite increase in heart failure (31%, CI 95% 24.8 to 37.2% for the placebo group vs 45%, CI 95% 38.2 to 51.7% for the Fluosol group, p=0.004) and a trend toward higher death and stroke rates were seen in the Fluosol group, while a reduction in recurrent ischemia and a tendency for less reinfarction were also evident (11%, CI 95% 6.8 to 15.2% for the placebo group vs 6%, CI 95% 2.8 to 9.2% for the Fluosol group, p=0.039). Fluosol administration was associated with significant preservation of fibrinogen, a lower platelet count, and no difference in leukocyte count and measures of anticoagulation. There was no significant difference in haemorrhagic complications.

Interpretation:

Among patients with acute myocardial infarction undergoing thrombolytic therapy, Fluosol administration was not associated with differences in infarct size reduction or improvement in systolic LV function compared with placebo.

References:

Wall TC, et al. Coronary Heart Disease/Myocardial Infarction: Intravenous Fluosol in the Treatment of Acute Myocardial Infarction: Results of the Thrombolysis and Angioplasty in Myocardial Infarction 9 Trial. Circulation 1994;90(1):114-120.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Vascular Medicine, Implantable Devices, EP Basic Science, Lipid Metabolism, Acute Heart Failure, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging

Keywords: Thrombolytic Therapy, Platelet Count, Leukocyte Count, Bronchial Spasm, Edema, Morphine, Atrioventricular Block, Research Personnel, Partial Thromboplastin Time, Fibrinogen, Tissue Plasminogen Activator, Nitroglycerin, Atropine, Outcome Assessment (Health Care), Myocardial Infarction, Stroke, Cardiac Catheterization, Heparin, Heart Rate, Reperfusion Injury, Coronary Angiography, Heart Failure, Thallium, Respiratory Sounds, Informed Consent, Fluorocarbons


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