Article Text
Abstract
Background Although not specifically targeted in the treatment of atherothrombotic syndromes, inflammation initiates, potentiates and destabilises atherosclerotic plaques. The inflammatory cytokine tumour necrosis factor α (TNF-α) is over expressed in unstable coronary plaques and is a potential therapeutic target in acute coronary syndromes.
Methods In a double-blind parallel group randomised controlled trial, 26 patients with acute myocardial infarction received an intravenous infusion of Etanercept (10 mg) or saline placebo. Differential leukocyte count, plasma cytokine concentrations, flow cytometric measures of platelet activation and peripheral resistance vessel vasomotor and fibrinolytic function were determined at before and 24 h after study infusion.
Results Treatment groups were well matched and similar at baseline. Placebo saline infusion did not alter any of the measurements at 24 h (p>0.1 for all). Consistent with effective antagonism of the TNF-α receptor, plasma TNF-α concentration increased in all patients following Etanercept infusion (254.3±14.7 vs 0.12±0.02 pg/ml, p<0.0001). At 24 h, Etanercept treatment reduced neutrophil counts (7.4±0.6 vs 8.8±0.6 cells 109/l, p=0.03) and plasma interleukin-6 concentrations (10.6±4 vs 5.8±2 pg/ml, p=0.012) whilst increasing platelet–monocyte aggregate formation (30.2±5.2 vs 20.3±2.9%, p=0.02); a marker of platelet activation. Vasodilatation in response to substance-P, acetylcholine and sodium nitroprusside, and tissue plasminogen activator release in response to substance P, were unaffected by either treatment (p>0.1 for all).
Conclusions In patients with acute myocardial infarction, Etanercept causes a modest anti-inflammatory effect, however this does not improve peripheral vasomotor or fibrinolytic function. Of concern, Etanercept caused an early increase in platelet activation suggesting potential adverse consequences of TNF-α antagonism in patients with acute coronary syndromes.
- TNF α
- antagonism, platelet monocyte binding, acute coronary syndromes