Objective The inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with acute myocardial infarction.
Design and setting and patients A double-blind, parallel group, randomised controlled trial performed in a tertiary referral cardiac centre. 26 patients presenting with acute myocardial infarction randomised to receive an intravenous infusion of etanercept (10 mg) or saline placebo.
Main outcome measures Leucocyte count, plasma cytokine concentrations, flow cytometric measures of platelet activation and peripheral vasomotor and fibrinolytic function were determined before and 24 h after study intervention.
Results Consistent with effective conjugation of circulating TNF-α, plasma TNF-α concentrations increased in all patients following etanercept (254±15 vs 0.12±0.02 pg/ml; p<0.0001), but not saline infusion. Etanercept treatment reduced neutrophil (7.4±0.6 vs 8.8±0.6×109 cells/l; p=0.03) and plasma interleukin-6 concentrations (5.8±2.0 vs 10.6±4.0 pg/ml; p=0.012) at 24 h but increased platelet–monocyte aggregation (30±5 vs 20±3%; p=0.02). Vasodilatation in response to substance P, acetylcholine and sodium nitroprusside, and acute tissue plasminogen activator release were unaffected by either treatment (p>0.1 for all).
Conclusions Following acute myocardial infarction, etanercept reduces systemic inflammation but increases platelet activation without affecting peripheral vasomotor or fibrinolytic function. We conclude that TNF-α antagonism is unlikely to be a beneficial therapeutic strategy in patients with acute myocardial infarction.
- MYOCARDIAL ISCHAEMIA AND INFARCTION (IHD)
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.