Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial.

Abstract

AIMS:

Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI).

METHODS AND RESULTS:

A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed.

CONCLUSIONS:

Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

• Authors: A Michael Lincoff, Matthew Roe, Philip Aylward, John Galla, Andrzej Rynkiewicz, Victor Guetta, Michael Zelizko, Neal Kleiman, Harvey White, Ellen McErlean, David Erlinge, Mika Laine, Jorge Manuel Dos Santos Ferreira, Shaun Goodman, Shamir Mehta, Dan Atar, Harry Suryapranata, Svend Eggert Jensen, Tamas Forster, Antonio Fernandez-Ortiz, Danny Schoors, Peter Radke, Guido Belli, Danielle Brennan, Gregory Bell, Mitchell Krucoff, PROTECTION AMI Investigators
• Journal: European heart journal (Eur Heart J) Vol. 35 Issue 37 Pg. 2516-23 (Oct 01 2014) ISSN: 1522-9645 [Electronic] England
• PMID: 24796339 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: [email protected].

Chemical References

• Biomarkers
• KAI 9803
• Peptides
• Protein Kinase Inhibitors
• Troponin I
• Creatine Kinase, MB Form

Topics

• Aged
• Area Under Curve
• Biomarkers (metabolism)
• Chemotherapy, Adjuvant
• Creatine Kinase, MB Form (metabolism)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Myocardial Infarction (therapy)
• Peptides (administration & dosage)
• Percutaneous Coronary Intervention (methods)
• Pilot Projects
• Protein Kinase Inhibitors (administration & dosage)
• Treatment Outcome
• Troponin I (metabolism)