Acute Myocardial Infarction Study of Adenosine II - AMISTAD II

Jul 09, 2003
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Date Presented:
01/01/2002
Date Published:
01/01/2005
Date Updated:
07/09/2003
Original Posted Date:
07/09/2003
References

Description:

A placebo controlled, phase III trial to compare the incidence of death and CHF in acute myocardial infarction patients treated with one of two doses of adenosine or placbo as an adjunct to thrombolysis or angioplasty.

Hypothesis:

The primary analysis will compare the two adenosine groups pooled with the placebo group. Patients treated with adenosine and reperfusion therapy with have a lower event rate than patients treated with placebo and reperfusion therapy.

Study Design

Study Design:

Patients Enrolled: 2,118
Mean Follow Up: 6 months
Mean Patient Age: >18 years

Patient Populations:

Acute anterolateral myocardial infarction; Symptom onset <=6 hours; Weight <119 kg; Age >18 years;

Primary Endpoints:

Composite of all-cause mortality, in-hospital congestive heart failure (>24 hours post-radomization), or re-hospitalization for CHF.

Secondary Endpoints:

All-cause mortality Cardiovascular mortality Infarct size measured by Tc-99m sestamibi SPECT imaging 120-168 hours post-randomization (600 patient subset).

Drug/Procedures Used:

Randomized to low dose intravenous adenosine (50 mcg/kg/min), high dose adenosine (70 mcg/kg/min) or placebo for 3 hours.

Concomitant Medications:

Patients will undergo reperfusion therapy (thrombolysis or mechanical reperfusion) within 15 minutes after initiation of study drug infusion.

Principal Findings:

The primary endpoint of death/CHF at 6 months did not differ between the pooled adenosine groups (16.3%) and the placebo group (17.9%, p=NS). Likewise, there was no difference between the placebo group and the low-dose group (16.5%) or the high-dose group (16.1%).

In the pre-specified subgroup analysis of patients with reperfusion success presented at the ACC 2002 meeting, a significant reduction in death/CHF was observed in the pooled adenosine group vs placebo (11% vs 15%, p=0.043). No difference in events occurred in patients with reperfusion failure (33% in adenosine group vs 34% in placebo group, p=0.771). Among patients treated within 2 hours, adenosine had a greater relative risk reduction than placebo (9% vs 13%). Benefit was not observed with adenosine when time to treatment was >4 hours (22% vs 20%).

Among the 243 patients in the imaging substudy with evaluable data, infarct size trended smaller in the pooled adenosine arms compared with placebo (17% vs 27%, p=0.074). The difference reached statistical significance in the high-dose adenosine group (11% vs 27%, p=0.023) but not in the low dose group (23% vs 27%, p=NS).

Interpretation:

Adjunctive adenosine therapy was not associated with a significant reduction in the primary endpoint of death or CHF by 6 months in patients treated standard reperfusion therapy for anterior MI. However, as with AMISTAD-I, infarct size was reduced with adenosine use, particuarly in the high-dose arm. The authors suggested the trial was underpowered to demonstrate a clinical benefit since the sample size was based on a 25% reduction in death or CHF and only an 11% reduction was observed.

References:

Ross AM, et al. A Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial of Adenosine as an Adjunct to Reperfusion in the Treatment of Acute Myocardial Infarction (AMISTAD-II). J Am Coll Cardiol 2005;45:1775– 80.

ACC March 2002, Atlanta, GA

Keywords: Coronary Disease, Anterior Wall Myocardial Infarction, Tissue Plasminogen Activator, Angioplasty, Stents


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