Acute Myocardial Infarction With Hyperoxemic Therapy II - AMIHOT II

Oct 23, 2007
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Trial Sponsor:
TherOx
Date Presented:
01/01/2007
Date Published:
01/01/2009
Date Updated:
10/23/2007
Original Posted Date:
10/23/2007
References

Description:

The goal of the trial was to evaluate the effect of supersaturated oxygen therapy following primary percutaneous coronary intervention (PCI) among patients with anterior myocardial infarction.

Study Design

Patients Enrolled: 301
Mean Follow Up: 30 days
Mean Patient Age: Mean age 60 years

Patient Populations:

Anterior myocardial infarction with primary PCI performed within 6 hours of symptom onset

Exclusions:

Cardiogenic shock, recent CPR, intra aortic balloon pump, increased bleeding risk, unsuccessful or complicated PCI

Primary Endpoints:

Infarct size at 14 days on SPECT using imputed values for patients without SPECT performed

Drug/Procedures Used:

Patients with acute anterior myocardial infarction (MI) undergoing primary PCI within 6 hours from symptom onset were randomized following successful PCI to either hyperoxemic reperfusion (n = 222) or control (n = 79). SPECT was performed at 14 days to evaluate infarct size. Although the overall AMIHOT 1 trial was negative, a subgroup of patients with anterior MI who were reperfused within 6 hours of symptom onset did show lower infarct size with hyperoxemic reperfusion. This subgroup was pooled with data from the current trial. Bayesian statistics were applied. The trial alone was not powered for the primary endpoint; it was only powered by pooling with the subgroup from AMIHOT 1.

In the hyperoxemic group, intracoronary hyperoxemic reperfusion was performed for 90 minutes using the TherOx® AO System (TherOx Inc., Irvine, California). Hyperoxemic therapy was performed by mixing 3 ml of aqueous oxygen (AO) with 70 ml/min of patient blood. The mixture was subsequently infused through a catheter in the infarct artery.

Principal Findings:

Median time from symptom onset to presentation was 109 minutes in the hyperoxemic group and 90 minutes in the control group; door to balloon time was 77 minutes. The infarct lesion was in the proximal LAD artery in 48% of patients. Stents were used in the large majority of patients (99%) and glycoprotein IIb/IIIa inhibitors were used in 67% of patients. At the end of the PCI, 88.4% of the hyperoxemic group and 93.0% of the control group had TIMI grade 3 flow.

SPECT at 14 days was performed in 78.8% of the hyperoxemic group and 87.3% of the control group. Patients with missing SPECT had infarct size imputed. The primary endpoint of infarct size did not differ between the hyperoxemic and control group when looking in the present study (median 20% for hyperoxemic group vs. 26.5%, p = 0.10). However, when pooling the present study with the subgroup from AMIHOT 1, infarct size was lower in the hyperoxemic group compared with the control group (median 18.5% vs. 25%, p = 0.023). MACE by 30 days occurred in 5.4% of the hyperoxemic group and 3.8% of the control group (p = 0.77). There were 4 deaths in the hyperoxemic group and none in the control group (p = 0.58). Bleeding related adverse events were higher in the hyperoxemic group compared with the control group (24.3% vs. 12.7%, p = 0.04), as were access site adverse events (22.5% vs. 12.7%, p = 0.07).

Interpretation:

Among patients with acute anterior MI undergoing primary PCI, use of supersaturated oxygen therapy post-PCI compared with control was not associated with a significant reduction in infarct size in the AMIHOT II trial, but hyperoxemic therapy was associated with a reduction in infarct size when pooling the positive subgroup from the overall negative AMIHOT I trial.

Although Bayesian statistics were applied, the addition of a positive subgroup from an overall negative trial to a second negative trial should be viewed with extreme caution. The reduction in infarct size in the pooled analysis should be viewed as hypothesis generating rather than conclusive. Bleeding related adverse events were higher in the hyperoxemic group, as were access site adverse events. There was no difference in overall MACE rates at 30 days.

[Note from the Editor-in-Chief: A Letter to the Editor regarding results of the AMIHOT II trial, as well as a corrected TCT 2007 presentation slide, are posted here.

References:

Presented by Dr. Gregg W. Stone. at TCT 2007, Washington, DC.

Stone GW, Martin JL, de Boer MJ, et al. Effect of supersaturated oxygen delivery on infarct size after percutaneous coronary intervention in acute myocardial infarction. Circ Cardiovasc Interv. 2009 Oct;2(5):366-75. Epub 2009 Sep 15.

Keywords: Myocardial Infarction, Tomography, Emission-Computed, Single-Photon, Bayes Theorem, Oxygen, Fluorocarbons, Stents, Percutaneous Coronary Intervention, Platelet Glycoprotein GPIIb-IIIa Complex


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