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 and Canada. 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 1980’s.
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.