Anti-TNFs found to reduce risk of acute coronary syndrome in rheumatoid arthritis patients

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. High risk of coronary heart disease in RA patients has been linked to inflammation and disease severity, making effective management of these factors highly important.

Anti-tumor necrosis factor drugs are a class of drugs that have been used for more than 10 years. They are used worldwide to treat inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, Crohn's colitis, ankylosing spondylitis and psoriasis. These drugs are able to reduce inflammation and stop disease progression.

Researchers in Sweden sought to determine if use of tumor necrosis factor inhibitor drugs to treat RA would result in a reduced risk of acute coronary syndrome (commonly called ACS), defined as a diagnosis of a heart attack or unstable angina (the worsening or increasing cardiac symptoms)

"As modern therapeutic alternatives in RA often make it possible to achieve a good control of joint inflammation, it is important to evaluate if this can also affect comorbidities," says Lotta Ljung, MD, senior consultant, rheumatology; Umea University Hospital; and lead investigator in the study. "Patients with RA have a doubled or so risk for acute coronary syndrome, and cardiovascular prevention is thus a major task for rheumatologists."

The researchers looked at the rates of coronary heart disease among RA patients using TNF inhibitors as compared to RA patients not using the drugs and the general population. The researchers identified a cohort of 7,704 RA patients from the Swedish Biologics Register with no previous incidence of ischemic heart disease who started their first TNF inhibitor between 2001 and 2010. The patients in this group were 75.9 percent female with an average age of 57.1 years. A comparator cohort of 23,112 matched, patients with RA who had never taken a biologic were identified from the National Patient Register. As a second comparator group, 38,520 matched individuals were randomly selected from the general population register.

Patient data was analyzed according to three periods of exposure to TNF inhibitors. "Actively" on TNF inhibitors was defined as taking the drugs until date of termination plus 90 days. "Short-term exposure" was defined as taking TNF inhibitors to two years. "Ever" was defined as having ever taken the medication. Acute coronary syndrome was defined as any primary discharge diagnosis of heart attack, unstable angina, or heart attack as cause of death from the Patient Register and the Cause-of-Death Register, respectively.

ACS occurred in the general population at a rate of 3.3/1,000 person-years, compared to 5.7 /1,000 person-years among those patients with RA actively on TNF inhibitor treatment and 8.6/1,000 person-years among those with RA who had never taken a biologic medication. Compared with the general population, and after controlling for confounding factors (such as disease duration, other co-existing diseases and socio-economic factors), patients with RA actively on TNF inhibitor treatment were 50 percent more likely to have ACS, while those who had never taken these medications were over twice as likely to have ACS. Compared to those who have never taken anti-TNF medication, the risk of ACS for patients actively on treatment was 27 percent lower. Similar risk estimates were observed in the other definitions of follow-up.

"This nationwide study adds to the evidence that use of TNF inhibitors for RA also has an impact on cardiovascular comorbidity," Dr. Ljung says. "Whether the lowered risk of ACS is attributable to the TNF inhibitors as such, or is an effect of better inflammatory control, cannot be determined from this study. The increase in risk of ACS in patients with RA was lower, but not abolished by the treatment. Therefore, individualized cardiovascular prevention is needed for most patients."