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Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT)
Author(s) -
RIDKER PAUL M.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03404.x
Subject(s) - medicine , inflammation , rheumatoid arthritis , myocardial infarction , c reactive protein , placebo , coronary artery disease , stroke (engine) , randomized controlled trial , cardiology , pathology , mechanical engineering , alternative medicine , engineering
Summary. While inflammation is a crucial component of atherothrombosis and patients with elevated inflammatory biomarkers such as high sensitivity C‐reactive protein (hsCRP) are at increased vascular risk, it remains unknown whether inhibition of inflammation per se will lower vascular event rates. The recently completed JUPITER ( N Engl J Med 2008, 359, 2195) trial demonstrates that statins reduce myocardial infarction, stroke, and all‐cause mortality among healthy individuals with low cholesterol and elevated hsCRP. However, a direct test of the inflammatory hypothesis of atherothrombosis requires an agent that inhibits inflammation without impacting other components of the atherothrombotic process, and has an acceptable safety profile for a trial setting. On this basis, the cardiovascular inflammation reduction trial (CIRT) proposes to allocate 7000 stable coronary artery disease patients with persistent elevations of hsCRP to placebo or very‐low‐dose‐methotrexate (VLDM, 10 mg weekly), a proven anti‐inflammatory regimen that reduces TNFα, IL‐6, and CRP levels and is in wide use among rheumatoid arthritis patients. If successful, CIRT would both confirm the inflammatory hypothesis of atherothrombosis and open novel approaches to the treatment and prevention of cardiovascular disorders.