Dr. Cohen presented findings from the Treatment of Enoxaparin and Tirofiban in Acute Myocardial Infarction (TETAMI) trial, which was designed to evaluate therapy with a low-molecular-weight form of heparin (enoxaparin) and a platelet IIb/III receptor blocker (tirofiban) for patients who had not been given reperfusion therapy. Data did not reveal any statistically significant differences between patients treated with enoxaparin vs. unfractionated heparin or with tirofiban vs. placebo. However, subgroup analysis indicated that enoxaparin might have benefit for patients with Killip class I infarcts (the smallest infarctions). Both enoxaparin and tirofiban might have benefit for patients within 12 hours of symptom onset.

The primary goal of the Treatment of Enoxaparin and Tirofiban in Acute Myocardial Infarction (TETAMI) trial was to see whether enoxaparin, a low-molecular-weight form of heparin, might have an advantage over unfractionated heparin for patients who had not been given reperfusion therapy because of duration of symptoms or inability to start reperfusion within 12 hours of symptoms onset. The secondary goal was to evaluate the efficacy of tirofiban, a platelet IIb/III receptor blocker, vs. placebo for the same patient group.

Thus, the study design required four distinct treatment arms. Overall, the study enrolled 1,224 patients. The four arms were equivalent in key traits, including comorbid conditions. With an average age of roughly 63 years, study patients were somewhat older than a typical group given reperfusion therapy. The presence of Q waves at enrollment for more than 66% of patients indicated that they were, indeed, past the earliest period of their infarction. The average time-to-treatment was 16-17 hours after symptom onset (cut-off for entry was 24 hours). The major reasons given for lack of reperfusion therapy was usually late arrival (greater than 12 hours after symptom onset), although some patients had initially presented at less than 12 hours but were referred because of unavailability of reperfusion at original facility.

Data analysis showed that the incidence of the primary clinical endpoint was 17.3% for unfractionated heparin and 15.4% for enoxaparin. The difference was negligible for tirofiban, with an incidence of adverse endpoint for 16.6% for tirofiban vs. 16.4% for placebo-treated patients.

Dr. Cohen identified two points for discussion from the statistically similar results on both agents. First, he noted that investigators did some post-hoc analyses to see whether any subgroups of patients within the larger, heterogeneous study population might have benefited from one or both agents. Second, he thought it merited discussion to explore the limitations of the TETAMI study in light of design of future trials for this difficult and diverse group of patients.

The researchers conducted two subanalyses regarding enoxaparin. They found evidence that there might be an outcome advantage with enoxaparin for patients with Killip class I infarcts (those with the smallest, lowest risk infarcts). Adverse rate was 13.5% for enoxaparin compared with 16.2% for heparin. In addition, there was a suggestion that there might be a benefit with enoxaparin for patients who presented earlier in the clinical course (within 12 hours of symptom onset).

Subanalysis regarding use of tirofiban indicated there might be an advantage with tirofiban for patients who presented within 12 hours of symptom onset.

Beyond an effort at defining and evaluating results for patient subgroups is an effort to appreciate the limitations of any study dealing with such a heterogeneous, high risk patient population. Dr. Cohen thought that interpretation of the TETAMI design and findings may point the way to design of future trials for patients for whom reperfusion is not an option. Although the TETAMI trial was the first major study for nonreperfused patients, it will not be the last.