Rheumatoid Arthritis May Double Venous Thromboembolism Risk

Janis C. Kelly

August 14, 2013

Rheumatoid arthritis (RA) was associated with a significantly increased risk for potentially fatal blood clots in the legs and lung, according to a nationwide prospective cohort study from Taiwan published online August 7 in the Annals of the Rheumatic Diseases. Therefore, venous thromboembolism (VTE) prophylaxis should be considered for patients with RA who are facing additional risk factors, such as surgery or hospitalization.

Wei-Sheng Chung, from the Department of Internal Medicine, Taichung Hospital, Department of Health, Executive Yuan, and the Department of Healthcare Administration, Central Taiwan University of Science and Technology, Taichung, Taiwan, and colleagues analyzed data from a cohort of 29,238 patients with RA and 116,952 matched control participants drawn from the Taiwan National Health Insurance Research Database.

They found, , that patients with RA were more than 3 times as likely to develop a deep venous thrombosis (DVT) during the 4 years after diagnosis as control subjects (hazard ratio [HR], 3.36; 95% confidence interval [CI], 2.79 - 4.03; P < .001), after adjusting for age, sex, and comorbidities. Moreover, the patients with RA were twice as likely to develop a pulmonary thromboembolism (PTE) as those without RA (HR, 2.07; 95% CI, 1.55 - 2.76; P < .001).

"Clinicians should be aware of these findings. To take holistic care of RA patients, a multidisciplinary team work approach is warranted," corresponding author Chia-Hung Kao, MD, from China Medical University's Graduate Institute of Clinical Medicine Science in Taiwan, told Medscape Medical News.

Excess Clot Risk Highest for Those Younger Than 50 Years

RA was associated with particularly high risk in those younger than 50 years, who were almost 6 times (HR, 5.55; 95% CI, 3.40 -9.07; P < .001) as likely to develop a DVT and more than 3 times (HR, 3.13; 95% CI, 1.26 - 7.77; P < .05) as likely to develop PTE as control subjects.

The researchers tracked the health of nearly the entire population of Taiwan (23.74 million people) through the country's compulsory national insurance scheme between 1998 to 2008 and included a further monitoring period up to the end of 2010 to find out whether RA increased the risk for potentially fatal blood clots. The authors note that VTE, which includes both PE and DVT, has a 30-day case fatality rate of 11% to 30% in previous studies.

The authors report that patients with RA also were more likely to have other underlying, potentially treatable, conditions such as hypertension, diabetes, high cholesterol, or heart failure, which might contribute to the increased thromboembolism risk. However, Dr. Kao emphasized to Medscape Medical News, the increased risk was apparent even after adjusting for age and comorbidities."[T]his nationwide study of approximately 30,000 patients with RA with 193,753 follow-up person-years shows that patients with RA have 3.36-fold and 2.07-fold increased risks of developing DVT and PE compared with the general population. These findings highlight the importance of a multidisciplinary team adopting an integrated approach to the intervention of potential risk factors among patients with RA," the authors write.

US Data Show Similar RA-Related Blood Clot Risk

"This study is consistent with what our study and other published papers found," Seoyoung C. Kim, MD, MSCE, told Medscape Medical News. Dr. Kim is assistant professor of medicine, Division of Pharmacoepidemiology and Pharmacoeconomics and Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Dr. Kim, who was not involved in the current study, published a retrospective cohort study online May 10 in Arthritis Care & Research showing that RA risk was associated with incidence rates 2.4 times higher for VTE and 2.7 times higher for PTE compared with non-RA patients. Dr. Kim's study cohort included 22,143 patients with RA and 88,572 patients without RA, drawn from US insurance claims data covering 28 million subscribers.

Dr. Kim said a strength of the Taiwanese study was the ability to focus on newly diagnosed RA. "While our study used prevalent cases of RA, they were able to look at the risk by time since RA diagnosis, as they had the new RA cohort," she said. A second strength was the mean follow-up time of more than 6 years in Dr. Kao's study compared with more than 2 years in Dr. Kim's study.

"Table 3 in their paper looked at the interaction between RA and comorbidity, which is interesting clinically. However, it is important to note the adjusted HR in that table was only adjusted for age and sex, and comorbidity was dichotomized (yes/no), which may be too simple," Dr. Kim said.

Time to Take VTE Prophylaxis More Seriously in RA

"Over the past few years, a number of studies including ours and this one showed an increased risk of VTE in patients with RA compared to those without RA. This risk may be related to RA disease (systemic inflammation) itself or the treatment that patients receive for RA. Regardless, physicians should keep in mind that patients with RA are at an increased risk of VTE," Dr. Kim said. She advised that patients with RA be placed on VTE prophylaxis when undergoing surgery or hospitalization, which also increase risk, or if they develop cancer.

"In our study, the majority of patients who developed VTE had a provoking event such as a new diagnosis of cancer, hospitalization, or surgery," Dr. Kim said.

The study was supported by grants from the study hospital, the Taiwan Department of Health Clinical Trial and Research Center of Excellence, the Taiwan Department of Health Cancer Research Center of Excellence, and the International Research-Intensive Centers of Excellence in Taiwan. The authors have disclosed no relevant financial relationships. Dr. Kim received research support from Pfizer and tuition support for the Pharmacoepidemiology Program at the Harvard School of Public Health funded by Pfizer and Asisa.

Ann Rheum Dis. Published online August 7, 2013. Abstract


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