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Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study
  1. Gareth J Padfield,
  2. Jehangir N Din,
  3. Elena Koushiappi,
  4. Nicholas L Mills,
  5. Simon D Robinson,
  6. Nicholas Le May Cruden,
  7. Andrew John Lucking,
  8. Stanley Chia,
  9. Scott A Harding,
  10. David E Newby
  1. British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
  1. Correspondence to Dr Gareth J Padfield, British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Chancellor's Building, Edinburgh EH16 4SU, UK; gareth.padfield{at}nhs.net

Abstract

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)

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