The National Heart, Lung and Blood Institute (NHLBI), a part of the National Institutes of Health, is launching the Cardiovascular Inflammation Reduction Trial (CIRT), an international multicenter trial designed to determine whether a common anti-inflammatory drug can reduce heart attacks, strokes and deaths due to cardiovascular (CV) disease in people at high risk for them.
CIRT will determine whether treatment with a drug specifically targeting inflammation reduces rates of CV events among adults who have had a heart attack within the past five years and who also have type 2 diabetes or metabolic syndrome. The trial will randomly assign participants to receive methotrexate given at 10 to 20 mg weekly for three to four years or a placebo.
Methotrexate is an inexpensive generic drug commonly used at low doses to treat rheumatoid arthritis. It is also used at higher doses to treat certain forms of cancers such as leukemias and lymphomas.
"This trial could have global impact by potentially changing treatment recommendations for millions of individuals with heart disease," said Gary H. Gibbons, MD, director of the NHLBI, in a release.
Each year, more than 2 million people in the U.S. have heart attacks or strokes, and many of them die, according to the NHBLI statement.
"If this generic drug, which is already on the market at low cost, proves effective for reducing risk of heart attacks, stroke or death, it has the potential for broad public health impact in saving lives and reducing disease," said Paul M. Ridker, MD, MPH, who will serve as principal investigator for CIRT. He is a professor of medicine at Harvard Medical School and director of the Center for Cardiovascular Disease Prevention at the Brigham and Women's Hospital in Boston.
Adults who have type 2 diabetes are much more likely to die of heart disease or stroke than people without type 2 diabetes. Metabolic syndrome, which strickens many people with type 2 diabetes and obesity, also raises the risk of MI and stroke. People with diabetes or metabolic syndrome typically have elevated blood levels of various markers of inflammation.
CIRT will enroll 7,000 patients at 350 to 400 sites across the U.S. and Canada over the next 2.5 years and will follow them for two to four years (average 2.5 years). Site selection will begin in November, and patient recruitment will start in March 2013.
Eligible participants who tolerate the drug without side effects over a five-week test period will be randomly assigned to receive standard care plus placebo or standard care plus low-dose methotrexate. Participants also will take folic acid, which is routinely given with methotrexate to prevent vitamin deficiencies.
In addition to measuring the number of strokes, heart attacks and heart-related deaths among participants, CIRT will determine if low-dose methotrexate reduces death from all causes and certain heart- and blood vessel-related conditions and events, including incident deep vein thrombosis, pulmonary embolism, atrial fibrillation, hospitalization for chest pain or congestive heart failure, non-surgical procedures or CABG and newly diagnosed type 2 diabetes. CIRT also will establish a blood and DNA bank to study the effect of low-dose methotrexate on a number of inflammatory biomarkers.