Direct Inhibition of δ-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute MI - DELTA MI – Presented at ACC 2007

Mar 25, 2007
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Date Presented:
01/01/2007
Date Updated:
03/25/2007
Original Posted Date:
03/25/2007
References

Description:

The goal of the trial was to evaluate treatment with the novel δ-protein kinase C inhibitor KAI-9803 compared with placebo among patients with ST-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI).

Study Design

Study Design:

Patients Enrolled: 154
Mean Follow Up: 6 months

Patient Populations:

Anterior ST-elevation MI, left anterior descending artery with occluded flow (TIMI flow grade 0 or 1), planned primary PCI

Drug/Procedures Used:

Patients were randomized 2:1 to KAI-9803 (n = 102) in one of four ascending doses (0.05, 0.5, 1.25, and 5.0 mg) or placebo (n = 52). Study drug was administered via two intracoronary injections, one prior to PCI and one post-PCI.

Principal Findings:

The median creatine kinase-myocardial band (CK-MB) area under the curve was consistent numerically, but nonsignificantly lower with KAI-9803 than with placebo at each of the dose groups (0.05 mg: 4001 vs. 4858 ng/ml; 0.5 mg: 5226 vs. 6934 ng/ml; 1.25 mg: 5740 vs. 7352 ng/ml; 5.0 mg: 6662 vs. 8230 ng/ml). Infarct size on SPECT at 14 days was numerically but nonsignificantly lower in the 0.5 mg groups and 1.25 mg groups than placebo (23% vs. 29.5% and 32.5% vs. 43.0%), but did not differ from placebo in the lowest dose group (25.5% vs. 33.5%) or the highest dose group (45.5% vs. 30.0%). Likewise, post-PCI TIMI myocardial perfusion grade 3 was more common in the KAI-9803 0.5 mg and 1.25 mg groups compared with placebo (72.2% vs. 53.8% and 69.6% vs. 45.4%), but did not differ from placebo in the low-dose group (60.0% vs. 72.7%) or the high-dose group (48.0% vs. 61.5%).

At 6-month follow-up, there was no difference in mortality or site-reported chronic heart failure. The frequency of serious adverse events was similar among the KAI-9803 and placebo groups. All patients received both injections of study medication.

Interpretation:

Among patients with ST-elevation MI undergoing primary PCI, treatment with the novel δ-protein kinase C inhibitor KAI-9803 via intracoronary injection was associated with numerical but nonsignificantly lower post-PCI CK-MB release compared with placebo.

Limited therapies have been successful in reducing reperfusion injury. The present trial was a small, first-in-man dose-escalation study and not powered for full efficacy or safety evaluation. There were some signals of efficacy with less CK-MB release post-PCI and smaller infarct size, although none of these reductions was significant. There was no signal of a safety hazard, but a much larger study would be needed to fully assess safety.

References:

Presented by Dr. Matthew T. Roe at the i2 Summit/American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.

Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Vascular Medicine, Acute Heart Failure, Interventions and Imaging, Interventions and Vascular Medicine, Computed Tomography, Nuclear Imaging

Keywords: Myocardial Infarction, Reperfusion Injury, Follow-Up Studies, Tomography, Emission-Computed, Single-Photon, Creatine Kinase, MB Form, Heart Failure, Protein Kinase C, Percutaneous Coronary Intervention


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