Display Settings:

Format

Send to:

Choose Destination
Am Heart J. 2011 Oct;162(4):597-605. doi: 10.1016/j.ahj.2011.06.012. Epub 2011 Sep 14.

Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS).

Author information

  • 1Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. pridker@partners.org

Abstract

BACKGROUND:

Inflammation contributes to all phases of the atherothrombotic process, and patients with elevated inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP) have increased vascular risk. Yet, it remains unknown whether direct inhibition of inflammation will reduce cardiovascular event rates.

DESIGN:

The CANTOS will evaluate whether interleukin-1β (IL-1β) inhibition as compared with placebo can reduce rates of recurrent myocardial infarction, stroke, and cardiovascular death among stable patients with coronary artery disease who remain at high vascular risk due to persistent elevations of hsCRP (>2 mg/L) despite contemporary secondary prevention strategies. Canakinumab is a human monoclonal antibody that selectively neutralizes IL-1β, a proinflammatory cytokine that plays multiple roles in the atherothrombotic process and that undergoes activation by the nucleotide-binding leucine-rich repeat-containing pyrin receptor 3 inflammasome, a process promoted by cholesterol crystals. Canakinumab significantly reduces systemic C-reactive protein and other inflammatory biomarker levels, is generally well tolerated, and is currently indicated for the treatment of inherited IL-1β driven inflammatory diseases such as the Muckle-Wells syndrome. In a multinational collaborative effort using an event-driven intention-to-treat protocol, CANTOS will randomly allocate 17,200 stable postmyocardial infarction patients with persistent elevation of hsCRP to either placebo or to canakinumab at doses of 50, 150, or 300 mg every 3 months, administered subcutaneously. All participants will be followed up over an estimated period of up to 4 years for the trial primary end point (nonfatal myocardial infarction, nonfatal stroke, cardiovascular death) as well as for other vascular events, total mortality, adverse events, and specific clinical end points associated with inflammation including new onset diabetes, venous thrombosis, and atrial fibrillation.

SUMMARY:

If positive, CANTOS would confirm the inflammatory hypothesis of atherothrombosis and provide a novel cytokine-based therapy for the secondary prevention of cardiovascular disease and new-onset diabetes.

Copyright © 2011 Mosby, Inc. All rights reserved.

PMID:
21982649
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk