title: Inflammation and thrombosis - testing the hypothesis with anti-inflammatory drug trials.
abstract: The hypothesis of atherosclerosis as an inflammatory process has been a leitmotiv in cardiology for the past 20 years, and has now led to the launch of clinical trials aimed at testing whether drugs that primarily target inflammation can reduce cardiovascular events. Inflammation indeed drives all phases of atherosclerosis, from inception, through progression, and ultimately acute thrombotic complications (plaque rupture and probably plaque erosion). Since plaque rupture and erosion cause most acute coronary syndromes, appropriately tuned anti-inflammatory treatments should limit myocardial infarction and cardiovascular death. Beyond interrupting inflammation-related plaque disruption, such treatments might, however, also ameliorate the propensity to thrombosis once the trigger (plaque rupture or erosion) has occurred. Several lines of evidence support this view: experimental data document the role of inflammation in platelet activation, tissue factor-mediated coagulation, hyperfibrinogenaemia, impaired activity of natural anticoagulants (including those expressed by endothelial cells), and reduced fibrinolytic activity. Supporting evidence also derives from the involvement of inflammation in venous thrombosis, a process that commonly occurs in the absence of traditional risk factors for atherosclerosis but is associated with several inflammatory diseases including obesity. Ongoing trials, in addition to evaluating effects on primary outcomes, will afford the opportunity to probe the possibility that anti-inflammatory interventions that yield salutary changes in biomarkers of the thrombotic/fibrinolytic balance also translate into reduction of clinical events.
authors.affiliation: Raffaele De Caterina, MD, PhD, Institute of Cardiology, "G. d'Annunzio" University - Chieti, C/o Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy, Tel.: +39 0871 41512, Fax: +39 0871 402817, E-mail: rdecater@unich.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.forename: Emilia
authors.initials: E
authors.lastname: D'Ugo
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000517:prevention & control*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents
keywords: Inflammation; colchicine; interleukin-1 receptor antagonist; methotrexate; thrombosis