Comparison of heart attack risk across biologic DMARDs

The risk of acute coronary syndrome varies little across individual bDMARDs in people with rheumatoid arthritis

INTRODUCTION
Rheumatoid arthritis (shortened to RA) is a chronic inflammatory disease that affects a person’s joints, and may cause pain and disability. RA can affect people of all ages, but the risk increases with age. RA is more common in women than men. A typical patient newly diagnosed with RA would be a woman in her fifties or sixties. It is well known that as well as joint inflammation, people with RA have an increased risk of developing certain other conditions, such as heart attacks and other heart diseases. For heart attacks, this increased risk is thought to be a result of a combination of factors, such as a higher rate of risk factors for heart attacks among people with RA. For instance, the proportion of people with RA who are smokers or have smoked in the past is higher than in the general population. There can also be direct effects of the RA disease on the cardiovascular system – for example, inflammation is linked to atherosclerosis, which causes a person’s arteries to harden and narrow.

For heart attacks in RA, the role of anti-rheumatic drugs – in particular the class of drugs often referred to as “biologics” (also called biological disease-modifying antirheumatic drugs, or shortened to bDMARDs) – has not been fully understood. On the one hand, by bringing down RA inflammation, they may lower an otherwise increased risk of heart attacks. On the other hand, some of these drugs have themselves been linked with cardiac or cardiovascular side effects, and might therefore increase the risk of heart attacks.

WHAT DID THE AUTHORS HOPE TO FIND?
The authors wanted to fill a knowledge gap. The goal was to compare the risk of heart attacks in people with RA who were using different biologic medications.

WHO WAS STUDIED?
The study looked at over 20,000 people with RA treated with a biologic medication between 2008 and 2018. These people were registered in clinical rheumatology registers in Denmark, Finland, Iceland, Norway, or Sweden.

HOW WAS THE STUDY CONDUCTED?
This was a study for which the authors used existing databases and registers in which patient records had been collected as part of routine clinical care. There was no interventional treatment, meaning that the study observed heart attack risks with these medications as they were actually used in clinical practice, not as part of
a clinical trial. The rheumatology registers contributed information about people’s treatment for their rheumatoid arthritis. National patient registers were used to get information about people’s other medical diagnoses (such as other cardiovascular conditions or medications) and to identify those who developed a heart attack. Finally, population registers were used to identify people who died during the period, as well as to select a comparator group for the RA patients, characterised by the same age and sex. The information from these registers was linked together and analysed. The authors followed each treatment course, and compared the heart attack risk for each biologic drug.

WHAT WERE THE MAIN FINDINGS OF THE STUDY?
The main finding was that the risks of heart attacks, at least in the short- and intermediate-term (1 and 2 years), did not vary much across individual biologic drugs. These results suggest that, when considering a person’s heart attack risk, it does not seem to matter which specific biologic drug is used for their RA.

ARE THESE FINDINGS NEW?
These findings are new in the way they were generated, and new in the sense that they cover all biologic anti-rheumatic medications. In contrast, most previous studies have compared drugs one-to-one, rather than all eight medications against each other. The authors did observe a moderate increased heart attack risk for people taking three of the medicines studied: abatacept, infliximab, and rituximab. This is new, and has not been reported before, but might be explained by residual confounding. This means there could be characteristics for these people which made them more likely to be treated with these drugs, and also more likely to develop a heart attack. For example, people taking abatacept and rituximab had longer disease duration and could have accumulated more inflammation, which is associated with cardiovascular risk. The analyses tried to take this into account, but it is difficult to formally rule out that such differences between the medication groups under study were completely removed.

WHAT ARE THE LIMITATIONS OF THE STUDY?
As mentioned above, there was a lack of precision for some variables such as disease duration. In addition, a further limitation is that the authors did not have access to information about people’s socio-economic data. This includes education level, sick leave, and disability pension. There was also no information on whether people were taking non-steroidal anti-inflammatory drugs (NSAIDs), nor was it possible to study the most recent class of anti-rheumatic medications (JAK inhibitors).

WHAT DO THE AUTHORS PLAN ON DOING WITH THIS INFORMATION?
Given that RA inflammation is probably an important contributor to the risk of heart attacks in RA, the authors are now studying how remission in RA is associated with the risk of heart attacks.

WHAT DOES THIS MEAN FOR ME?
If you have rheumatoid arthritis, you may be more at risk of a heart attack than people in the general population. However, when looking at how your medicines might affect this risk, there is no reason to prefer one biologic anti-rheumatic drug over another.

If you have any concerns about your disease or its treatment, you should talk to your doctor.

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Date prepared: May 2022
Summary based on research article published on: 22 March 2022
From: Delcoigne B, et al. Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries. Ann Rheum Dis 2022;81(6):789–797. doi:10.1136/annrheumdis-2021-221996

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