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, or450 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 kinaseMB 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 STsegment 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. Clinical trial registration ClinicalTrials.gov Identifier: NCT00785954.
Original language | English |
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Pages (from-to) | 2516-2523 |
Number of pages | 8 |
Journal | European Heart Journal |
Volume | 35 |
Issue number | 37 |
DOIs | |
State | Published - 1 Oct 2014 |
Externally published | Yes |
Funding
Funders | Funder number |
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12Canadian Heart Research Centre | |
5Heart Institute | |
DeBakey Heart & Vascular Center | |
Department of Medicine | |
Hamilton General Hospital Hamilton | |
KAI Pharmaceuticals | |
Oslo University Hospital | |
Radboud University Nijmegen Medical Center | |
Bristol-Myers Squibb | |
Sons of Norway Foundation | |
Cleveland Clinic | C5Research |
City, University of London | |
Institute of Clinical and Translational Sciences | |
University of California, San Francisco | |
Lunds Universitet | |
Oslo University College |
Keywords
- Myocardial
- Myocardial infarction
- Pharmacology
- Reperfusion
- Stents
- Stunning