A new Swedish study published in the journal Annals of the Rheumatic Diseases suggests that optimizing control of rheumatoid arthritis (RA) disease may help lower overall risk for acute coronary syndrome (ACS) in those with RA. 

Lotta Ljung, MD, PhD,  a senior consultant in rheumatology at Umeå University Hospital, Umeå, Sweden, and colleagues evaluated a population-based cohort of patients diagnosed with RA and found that good, but not moderate, response to tumor necrosis factor inhibitors (TNFi) may be associated with a 50% lower risk for ACS compared with those who had no response to TNFi.1 

Data indicated that the short-term risk among those who had good response to TNFi treatment was similar to the risk for ACS in the general population. Those who did not respond to TNFi, and even those with moderate response, had an increased risk for ACS compared with the general population.


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The researchers examined whether the increased risk for cardiovascular disease in those with RA can be lowered by particular antirheumatic pharmacotherapies. From the Swedish biologics register, they identified a cohort of patients diagnosed with RA who underwent therapy with a first TNFi between 2001 and 2012.

The team analyzed the association between European League Against Rheumatism (EULAR) guidelines response after 3 to 8 months of treatment and the risk for incident ACS during the subsequent year. Disease Activity Score 28 (DAS28) was used to measure response. 

High Yield Clinical Pearls

  • EULAR good responders had no statistically significant difference in ACS risk vs the general population
  • Optimal RA disease control may negate otherwise increased ACS risk in RA

Patients were assessed based on the first response to DAS28, the best response to DAS28, and the DAS28 measurement closest to 5 months after initiation of TNFi. The investigators used Cox regression models and adjusted for cardiovascular risk factors, joint surgery, RA duration, education level, and work disability.

Researchers evaluated 6864 patients with RA. The mean age of this cohort was 55 years, and 77% were female. During 6592 person-years, 47 ACS occurred. The adjusted hazard ratios (95% confidence interval) for the 1-year risk for ACS among EULAR good responders compared with nonresponders were 0.5 (0.2 to 1.4) for the first assessment, 0.4 (0.2 to 0.9) for the best assessment, and 0.5 (0.2 to 1.2) for the evaluation closest to 5 months.

The study showed that the risk for those with moderate response according to EULAR guidelines was equal to that of EULAR nonresponders when compared with general population comparators (N = 34,229) who were matched for age, sex, and country of residency at the time of TNFi initiation. Both moderate responders and nonresponders were found to have a more than twofold increased risk for ACS.

“We found that a good response [to treatment with] TNFi in RA was associated with lower risk for ACS. In fact, among good responders, no increased risk was observed compared with the risk in the general population,” Dr Ljung said.

“By contrast, patients with limited or no response had a two[fold] to threefold risk for ACS compared with the background risk. As coronary disease is the main comorbidity in patients with RA, this is important knowledge.”

Summary and Clinical Applicability

This study provides evidence that a good response to TNFi therapy provides a protective effect on the short-term risk for ACS. The study suggests that reaching optimal control of disease activity may help prevent ischemic heart disease in those with RA. 

“We have previously shown an association between TNFi treatment and a lower risk of ACS in RA2,” Dr. Ljung told Rheumatology Advisor. “The aim in the present study was to further evaluate this association, whether it was a matter of the treatment as such or the response or lack of response on the treatment. The results tell us that we need to get optimal disease control to potentially normalize the cardiovascular risk in RA.”

Limitations and Disclosures

Whereas the fully adjusted regression models were adjusted for traditional cardiovascular disease risk factors, information such as presence of dyslipidemia and hereditary factors was only available for subsets of patients.

n addition, the observational nature of the study limits any conclusions about causality between TNFi-mediated response and ACS risk. The authors note that the association may be influenced by other changes in pharmacotherapy or lifestyle factors among responders. 

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References

1. Ljung L, Rantapää-Dahlqvist S, Jacobsson LT, Askling J; ARTIS Study Group. Response to biological treatment and subsequent risk of coronary events in rheumatoid arthritis. Ann Rheum Dis. 2016 Mar 16. [Epub ahead of print] doi: 10.1136/annrheumdis-2015-208995

2. Ljung L, Askling J, Rantapää-Dahlqvist S, Jacobsson L; ARTIS Study Group. The risk of acute coronary syndrome in rheumatoid arthritis in relation to tumour necrosis factor inhibitors and the risk in the general population: a national cohort study. Arthritis Res Ther. 2014;16(3):R127. doi: 10.1186/ar4584