Abstract | BACKGROUND: METHODS AND RESULTS: In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein ( hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means ( elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035). Elafin had no effect on myocardial infarction ( elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320). CONCLUSIONS: TRIAL REGISTRATION NUMBER: (EudraCT 2010-019527-58, ISRCTN82061264).
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Authors | S R Alam, S C Lewis, V Zamvar, R Pessotto, M R Dweck, A Krishan, K Goodman, K Oatey, R Harkess, L Milne, S Thomas, N M Mills, C Moore, S Semple, O Wiedow, C Stirrat, S Mirsadraee, D E Newby, P A Henriksen |
Journal | Heart (British Cardiac Society)
(Heart)
Vol. 101
Issue 20
Pg. 1639-45
(Oct 2015)
ISSN: 1468-201X [Electronic] England |
PMID | 26310261
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. |
Chemical References |
- Elafin
- Protease Inhibitors
- Recombinant Proteins
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Topics |
- Coronary Artery Bypass
(adverse effects)
- Coronary Artery Disease
(surgery)
- Double-Blind Method
- Elafin
(administration & dosage)
- Follow-Up Studies
- Humans
- Infusions, Intravenous
- Intraoperative Complications
(drug therapy, etiology)
- Intraoperative Period
- Magnetic Resonance Imaging, Cine
- Myocardial Reperfusion Injury
(diagnosis, drug therapy, etiology)
- Protease Inhibitors
(administration & dosage)
- Recombinant Proteins
- Retrospective Studies
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