Double therapy in rheumatoid arthritis linked to reduced heart, stroke risk

According to new research evaluating the drugs commonly used by rheumatoid arthritis (RA) patients, two specific combinations may be effective in lowering the risk of heart disease and stroke.

The study published in Frontiers in Cardiovascular Medicine, revealed that anti-rheumatic drug regimens that include either tumour necrosis factor inhibitors or the antimalarial drug hydroxychloroquine may significantly protect the endothelium in patients with RA. [ doi.org/10.3389/fcvm.2021.681327.]

Called the Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis (EDRA) study, the research looked at 868 RA patients, and five different types of anti-rheumatic drug groups were evaluated for their endothelial function protective properties. EDRA is a multicentre study led by the University of Sassari, Italy, in collaboration with University of Flinders, Australia.

According to the study’s lead investigator and national coordinator of the EDRA study Professor Gian Luca Erre: “Rheumatoid arthritis patients have an increased risk of atherosclerosis and cardiovascular disease when compared to the general population, probably due to an excess of inflammation in patients with this condition.”

“This excess of inflammation is not limited to the joints, but also involves the blood vessels leading to dysfunction in the [endothelium],” said Erre.

Drugs prescribed for RA typically have anti-inflammatory effects and may potentially protect the endothelium, reducing the risk of atherosclerosis in these patients. However, Erre noted that most patients take several anti-rheumatic drugs at once. “Hence, it is difficult to see which specific agent is better than others at protecting the endothelium.”

The EDRA study found that endothelial function was best preserved in those taking  anti-rheumatic drug regimens that included either tumour necrosis factor inhibitors or the antimalarial drug hydroxychloroquine. “Prospective studies are now required to test whether such regimens are also able to curb the risk of heart attack and stroke in these patients,” said Professor Arduino Mangoni, of Flinders University. He added: “Drugs used to treat RA’s debilitating pain in millions of patients around the world might have protective cardiovascular effects however these can be variable, as also shown in our study.”

According to Dr Amir Azlan Zain, specialist in internal medicine and rheumatology, the increased atherosclerotic risk in inflammatory rheumatic musculoskeletal diseases has been known for at least 25 years. The advent of biologic treatments posed the question whether these treatments would modify the cardiovascular (CV) risk. “Generally speaking, rheumatologists accept that tight RA control would lead to reduction in CV risk.”

Amir noted that endothelial dysfunction is central to this increased CV risk and this study seems to report improved endothelial protection though the mechanism of action is unclear. Whether this then translates to improved CV risk would need further longer-term data.

In closing, Amir said: “I do not think this would influence treatment options for us. The advent of new treatment modalities is leading to improved inflammatory/ disability outcomes, which remains our primary focus. At present we assume good RA control equals good CV risk reduction, but if there is epidemiological [not laboratory] data that a treatment type has better CV outcomes whilst maintaining good disease control then it would be a compelling reason to influence treatment choice.”