Press Release - Aug 22, 2012
Brigham and Women’s Hospital Researchers Initiate Major Cardiovascular Inflammation Reduction Trial
New study is "end-game" for 15 years of research examining the link
between inflammation and heart disease
Fifteen years ago, researchers at Brigham and Women's Hospital (BWH) reported
that C-reactive protein (CRP), a biomarker of inflammation found in the blood,
was as powerful a tool to predict future heart attack and stroke as was total
cholesterol. Today, the same research group announces the launch of a new
randomized clinical trial, funded by The
National Heart, Lung, and Blood Institute (NHLBI), a part of the National Institutes of Health (NIH), to determine
whether lowering inflammation with a common anti-inflammatory drug will in turn
reduce rates of recurrent heart attack, stroke, and cardiovascular death in
high risk patients who have already suffered a prior heart attack.
"We are exceptionally grateful to the National Heart, Lung,
and Blood Institute for funding the Cardiovascular Inflammation Reduction
Trial" said Paul
M Ridker, MD, principal investigator for the new trial and Director of the
Center for Cardiovascular Disease Prevention at BWH in Boston. "We believe that
the concept of reducing inflammation has enormous potential as a new method to
reduce the burden of heart attack and stroke for our patients."
The Cardiovascular Inflammation Reduction Trial (CIRT) will
test whether low-dose methotrexate [Trexall® (methotrexate tablets USP)], an inexpensive drug
widely used to treat rheumatoid arthritis, can reduce the rates of recurrent
cardiovascular events among patients with a prior heart attack who also have
diabetes or metabolic syndrome, conditions known to be associated with a heightened
inflammatory response. Such individuals
are at very high risk for second and third cardiac events which are often
life-threatening, despite all currently available interventions including
aggressive cholesterol reduction with statin therapy.
Researchers will enroll 7,000 patients from up to 400 clinical
sites across the United States
All patients will receive aggressive standard of care and in addition, half
will receive low-dose methotrexate (target dose of 20 mg/week) while the other
half will receive a placebo. All participants will be followed for 3 to 5 years
for recurrent major cardiovascular events.
"Prior research suggests that inflammation plays a critical
role in heart attack and stroke," said Gary H. Gibbons, M.D., director of the
NHLBI, which is funding the study. "This
trial promises to offer evidence about the relative importance of inflammation
and may lead to new treatment paradigms for millions of people with
cardiovascular disease," added Dr. Gibbons.
"This new study is
the end-game for more than fifteen years of research by investigators worldwide
demonstrating that inflammation is a central part of the process that leads to
heart attack and stroke," Dr. Ridker said. "Whether or not reducing that
inflammation can benefit our patients is unknown, but a positive finding in
this trial has the potential to dramatically reshape how we think about and
treat heart disease."
The concept of treating inflammation to prevent chronic
disease has a long history at BWH in Boston. In addition to Dr. Ridker's work,
BWH researchers Dr. Peter Libby, chief of the Division of Cardiology, and Dr.
Michael Gimbrone, director of Center for Excellence in Vascular Biology, performed
ground-breaking work investigating basic mechanisms of inflammation in heart
disease. Additionally, low-dose methotrexate as a treatment for rheumatoid
arthritis was pioneered at BWH by Dr. Michael Weinblatt and others in the
Screening will begin in January 2013 with patient
recruitment in March, 2013. Physicians
and clinical sites interested in CIRT can obtain further information at www.theCIRT.org.
Additional researchers involved in the CIRT trial include
Drs. Brendan Everett, Aruna Pradhan, Nina Paynter, Dan Solomon, and Robert
Glynn from BWH.
This study is funded by grants 1 U01 HL101422-01A1 and 1 U01
HL101389-01A1 from The National Heart, Lung, and Blood Institute (NHLBI), a
part of the National Institutes of Health (NIH).
Dr. Ridker is listed as a co-inventor on patents held by BWH
that relate to the use of inflammatory biomarkers in cardiovascular disease
that have been licensed to AstraZeneca and Siemens Healthcare Diagnostics in
the therapeutic and diagnostics field respectively. However, neither Dr. Ridker nor BWH receives
any royalties related to these patents or to the CRP test in connection with
the NIH-funded Cardiovascular Inflammation Reduction Trial (CIRT).
Trexall® (methotrexate tablets
USP) will be provided by Teva Pharmaceuticals and is a registered trademark of
Barr Laboratories, Inc.
Cardiovascular Center of Excellence