Clinical Research Center at Marshfield Clinic Research Institute was an integral part in research that has recently shown that taking low-dose methotrexate does not reduce additional cardiovascular events in patients with either diabetes or metabolic syndrome.

The Cardiovascular Inflammation Reduction Trial (CIRT) was a 5-year study conducted by the National Institutes of Health (NIH). The Research Institute was a research site for the study. The findings were recently published in the New England Journal of Medicine.

“Inflammation contributes to atherosclerosis, or cardiovascular events,” said Dr. Mateen Abidi, principal investigator for the study at the Research Institute and cardiologist at Marshfield Clinic Health System. “The NIH has been researching inflammation and its role in cardiovascular events over a period of more than 20 years.”

Canakinumab has already been shown to reduce cardiovascular events in those with diabetes by reducing inflammation, but this medication is an expensive option.

Low-dose methotrexate is a common medication taken by patients with rheumatoid arthritis to reduce inflammation. CIRT researchers wanted to see if this less expensive medication could reduce cardiovascular events similar to canakinumab.

“In research language we note this as a negative trial, meaning it did not help with cardiovascular events,” said Dr. Abidi. “However in a positive way, it did teach future researchers that the inflammatory hypothesis and questions have to be focused on targeting specific anti-inflammatory markers.”

The genetic markers that are known to be connected to atherosclerosis and inflammation are the c-reactive protein, interleukin 1B and interleukin 6. The study looking at canakinumab did target interleukin 6.

The CIRT study also has led researchers to question why patients with rheumatoid arthritis that take low-dose methotrexate have lower incidences of cardiovascular events.

“Maybe in patients that have active rheumatoid arthritis and you inhibit it at an active stage, you see the results,” Dr. Abidi said. This, and many other hypotheses, is yet to be answered surrounding cardiovascular events.

Special recognition

The Research Institute team that worked on CIRT was recognized by the NIH for having an equal balance of male and female participants. This is an important factor because males tend to participate in research more frequently than females.

Not only did the Research Institute participate in the CIRT study, but it also played an integral part in a research study that led to the CIRT study.

“In a study published in 2005, Research Institute researchers and others across the nation found that if you take a medication to decrease cholesterol or a medication that reduced the c-reactive protein, you could reduce cardiovascular events,” said Dr. Shereif Rezkalla, cardiologist at Marshfield Clinic Health System, and investigator for CIRT and the 2005 study. “The research also found that if you could do both, the chance of cardiovascular events were even less.”