A Swedish study has found that treatment with tumor necrosis factor-alpha inhibitors, or anti-TNFs, does not lower the risk of heart attacks and unstable angina – a type of chest pain that may lead to a heart attack – in patients with early rheumatoid arthritis.

It’s well known that rheumatoid arthritis, or RA, increases the risk of cardiovascular disease, but it is unclear whether anti-TNFs reduce that risk. TNF inhibitors – adalimumab, or Humira; etanercept, or Enbrel; infliximab, or Remicade; certolizumab pegol, or Cimzia; and golimumab, or Simponi – are biologic medications that block a cytokine linked to inflammation. Chronic inflammation is believed to play a large role in cardiovascular disease.

Previous studies on these drugs’ effects on cardiovascular risk show mixed results. Several studies have shown that anti-TNFs do lower the risk of cardiovascular disease in patients with established RA. But the new study, published online in Arthritis & Rheumatism, shows that benefit doesn’t extend to early RA patients – at least not in the specific category of acute coronary syndromes, or ACS, which includes heart attacks and unstable angina.

“I would not hesitate to treat the inflammatory disease with an anti-TNF when it is indicated, but, as a rheumatologist, I must be aware that this alone might not be enough to normalize the risk for myocardial infarction [heart attack] for my patient,” explains lead author Lotta Ljung, MD, a senior consultant in rheumatology at Umeå University Hospital in Umeå, Sweden.

For this latest study, Dr. Ljung and colleagues identified 6,000 patients from a national Swedish database who were treated within a year of developing RA symptoms. Within this group, they found 173 first-time ACS events. They then calculated the risks of heart attack or unstable angina for those taking and not taking anti-TNFs. Ultimately they didn’t find any statistically significant differences in risk between the two groups.

After performing a second analysis, the researchers also failed to find a difference in risk for ACS between those patients who had responded to anti-TNF therapy and those who had not respond.

Dr. Ljung says her team’s findings could be different from earlier studies showing a protective effect of anti-TNFs on the heart because of different patient populations and the fact that previous research is based on a broader definition of cardiovascular risk than her team used.

“Two of the main differences between our study and most previously published studies showing a decrease in risk are that the patients in our study had shorter disease duration, and that we defined the events as myocardial infarction or unstable angina, the two diagnoses that constitute acute coronary events,” says Dr. Ljung. “The accumulated burden of disease is lower early in the course, which might be one explanation of the difference.

“The most important message for our patients and for rheumatologists, I think, is that we should continue to measure and control known risk factors in order to minimize the cardiovascular risk, whether the patients are treated with anti-TNFs or not,” Dr. Ljung says.

Jon Giles, MD, an assistant professor of medicine in the division of rheumatology at Columbia University’s College of Physicians and Surgeons, was lead author of a study (when he was at Johns Hopkins University) that found TNF inhibitors reduced the amount of carotid artery thickening, a sign of plaque build-up. He agrees that all of these studies are looking at different groups of patients and different cardiovascular outcomes.

“We didn’t look at events in our study. We looked at progression of carotid atherosclerosis. So they could be different patients with RA,” Dr. Giles says.

But he also cautions against drawing too many conclusions from this study because he says TNF inhibitors are often given to patients with more extreme levels of inflammation, so the baseline of the two groups could have been different.

“It’s the problem of an observational study,” Dr. Giles says. “People taking anti-TNF medications may be at higher overall cardiovascular risk. People taking other medications may be at lower cardiovascular risk; thus, equivalent results could mean (the two groups) didn’t start at the same point but ended at the same point. There very well could be a benefit you aren’t picking up because you didn’t realize their risk of cardiovascular events was not equal at the beginning.”

Dr. Giles says the important thing for any RA patient to know is that maximal control of RA disease activity, regardless of what agent is used, is likely to improve cardiovascular outcomes in conjunction with control of traditional risk factors, such as high blood pressure, cholesterol, smoking, diabetes, and obesity.