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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

Lincoff, A. Michael; Roe, Matthew; Aylward, Philip; Galla, John; Rynkiewicz, Andrzej; Guetta, Victor; Zelizko, Michael; Kleiman, Neal; White, Harvey and McErlean, Ellen, et al. (2014) In European Heart Journal 35(37). p.2516-2523
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... (More)
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 similar to 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. (Less)
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published
subject
keywords
Reperfusion, Myocardial infarction, Stunning, Myocardial, Stents, Pharmacology
in
European Heart Journal
volume
35
issue
37
pages
2516 - 2523
publisher
Oxford University Press
external identifiers
  • wos:000343325300010
  • scopus:84907396129
ISSN
1522-9645
DOI
10.1093/eurheartj/ehu177
language
English
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yes
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5126605d-0eb0-4d58-a6e8-b6ccbe33e5dd (old id 4787351)
date added to LUP
2014-12-01 07:36:20
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2017-10-29 03:51:24
@article{5126605d-0eb0-4d58-a6e8-b6ccbe33e5dd,
  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 similar to 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.},
  author       = {Lincoff, A. Michael and Roe, Matthew and Aylward, Philip and Galla, John and Rynkiewicz, Andrzej and Guetta, Victor and Zelizko, Michael and Kleiman, Neal and White, Harvey and McErlean, Ellen and Erlinge, David and Laine, Mika and dos Santos Ferreira, Jorge Manuel and Goodman, Shaun and Mehta, Shamir and Atar, Dan and Suryapranata, Harry and Jensen, Svend Eggert and Forster, Tamas and Fernandez-Ortiz, Antonio and Schoors, Danny and Radke, Peter and Belli, Guido and Brennan, Danielle and Bell, Gregory and Krucoff, Mitchell},
  issn         = {1522-9645},
  keyword      = {Reperfusion,Myocardial infarction,Stunning,Myocardial,Stents,Pharmacology},
  language     = {eng},
  number       = {37},
  pages        = {2516--2523},
  publisher    = {Oxford University Press},
  series       = {European Heart Journal},
  title        = {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},
  url          = {http://dx.doi.org/10.1093/eurheartj/ehu177},
  volume       = {35},
  year         = {2014},
}