Accumulating evidence of risk
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Venous thromboembolism risk increased with rheumatoid arthritis

Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.

Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.

Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.

Courtesy Dr. Chia-Hung Kao
Dr. Wei-Sheng Chung

In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.

After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).

The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.

Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.

"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.

In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.

Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.

The study cohort was 77% female and had a mean age of 52 years.

The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.

Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.

Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

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This study is consistent with the findings of our U.S. study of 110,715 patients (Arthritis Care Res. 2013 May 10 [doi:10.1002/acr.22039]) and other published papers. Over the past few years, a number of studies, including ours and this one, have shown an increased risk of venous thromboembolism in patients with rheumatoid arthritis, compared with those without rheumatoid arthritis. This risk may be related to rheumatoid arthritis disease (systemic inflammation) itself or the treatment that patients received for rheumatoid arthritis.


Dr. SeoYoung C. Kim

Regardless, physicians should keep in mind that patients with rheumatoid arthritis are at increased risk of venous thromboembolism. When rheumatoid arthritis patients go through other known risk factors for venous thromboembolism (surgery, cancer diagnosis, hospitalization), they should be properly placed on venous thromboembolism prophylaxis.

According to this Taiwanese study, the risk of deep vein thrombosis was the highest in the first years after rheumatoid arthritis diagnosis.

The Taiwanese study focused on newly diagnosed rheumatoid arthritis, while our study used prevalent cases of rheumatoid arthritis. They were able to look at the risk by time since rheumatoid arthritis diagnosis. Overall, the mean follow-up time was quite long (over 6 years), whereas our study has over 2 years of follow-up on average.

The Taiwanese findings regarding the interaction between rheumatoid arthritis and comorbidity is interesting clinically, but it is important to note that their adjusted hazard ratio was adjusted only for age, sex, and comorbidity, which was made into a dichotomized (yes/no) variable, which may be too simple.

The Taiwanese study reported that around 7% of patients had hypertension, which seems somewhat low, given that the mean age of the cohort was 52 years. Our cohort had the same mean age and 24%-30% had hypertension. We excluded patients with cancer at baseline, and the Taiwanese study included them.

As the Taiwanese investigators write in the discussion section of their report, the lack of data on some known risk factors such as oral contraceptive use, steroids, and other drugs would lead to incomplete adjustment for confounding.

Because both studies used mainly claims data, it is important to adjust for health care use patterns to minimize surveillance bias. In other words, patients without rheumatoid arthritis may not seek medical care as much as rheumatoid arthritis patients. Physicians may behave differently when they have a patient with possible venous thromboembolism symptoms in the presence or absence of rheumatoid arthritis. My guess is that, if the Taiwanese study does further adjustment for health care use, the hazard ratio would get smaller.

Further research is needed to evaluate whether or not the additional venous thromboembolism risk in patients with rheumatoid arthritis can be modified by disease-modifying antirheumatic drugs or other factors (such as physical activity, obesity, or smoking).

Dr. SeoYoung C. Kim is assistant professor of medicine at Brigham and Women’s Hospital, Boston. Her study was funded by the National Institutes of Health. She has received research support from Pfizer and tuition support from the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium, and ASISA.

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This study is consistent with the findings of our U.S. study of 110,715 patients (Arthritis Care Res. 2013 May 10 [doi:10.1002/acr.22039]) and other published papers. Over the past few years, a number of studies, including ours and this one, have shown an increased risk of venous thromboembolism in patients with rheumatoid arthritis, compared with those without rheumatoid arthritis. This risk may be related to rheumatoid arthritis disease (systemic inflammation) itself or the treatment that patients received for rheumatoid arthritis.


Dr. SeoYoung C. Kim

Regardless, physicians should keep in mind that patients with rheumatoid arthritis are at increased risk of venous thromboembolism. When rheumatoid arthritis patients go through other known risk factors for venous thromboembolism (surgery, cancer diagnosis, hospitalization), they should be properly placed on venous thromboembolism prophylaxis.

According to this Taiwanese study, the risk of deep vein thrombosis was the highest in the first years after rheumatoid arthritis diagnosis.

The Taiwanese study focused on newly diagnosed rheumatoid arthritis, while our study used prevalent cases of rheumatoid arthritis. They were able to look at the risk by time since rheumatoid arthritis diagnosis. Overall, the mean follow-up time was quite long (over 6 years), whereas our study has over 2 years of follow-up on average.

The Taiwanese findings regarding the interaction between rheumatoid arthritis and comorbidity is interesting clinically, but it is important to note that their adjusted hazard ratio was adjusted only for age, sex, and comorbidity, which was made into a dichotomized (yes/no) variable, which may be too simple.

The Taiwanese study reported that around 7% of patients had hypertension, which seems somewhat low, given that the mean age of the cohort was 52 years. Our cohort had the same mean age and 24%-30% had hypertension. We excluded patients with cancer at baseline, and the Taiwanese study included them.

As the Taiwanese investigators write in the discussion section of their report, the lack of data on some known risk factors such as oral contraceptive use, steroids, and other drugs would lead to incomplete adjustment for confounding.

Because both studies used mainly claims data, it is important to adjust for health care use patterns to minimize surveillance bias. In other words, patients without rheumatoid arthritis may not seek medical care as much as rheumatoid arthritis patients. Physicians may behave differently when they have a patient with possible venous thromboembolism symptoms in the presence or absence of rheumatoid arthritis. My guess is that, if the Taiwanese study does further adjustment for health care use, the hazard ratio would get smaller.

Further research is needed to evaluate whether or not the additional venous thromboembolism risk in patients with rheumatoid arthritis can be modified by disease-modifying antirheumatic drugs or other factors (such as physical activity, obesity, or smoking).

Dr. SeoYoung C. Kim is assistant professor of medicine at Brigham and Women’s Hospital, Boston. Her study was funded by the National Institutes of Health. She has received research support from Pfizer and tuition support from the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium, and ASISA.

Body

This study is consistent with the findings of our U.S. study of 110,715 patients (Arthritis Care Res. 2013 May 10 [doi:10.1002/acr.22039]) and other published papers. Over the past few years, a number of studies, including ours and this one, have shown an increased risk of venous thromboembolism in patients with rheumatoid arthritis, compared with those without rheumatoid arthritis. This risk may be related to rheumatoid arthritis disease (systemic inflammation) itself or the treatment that patients received for rheumatoid arthritis.


Dr. SeoYoung C. Kim

Regardless, physicians should keep in mind that patients with rheumatoid arthritis are at increased risk of venous thromboembolism. When rheumatoid arthritis patients go through other known risk factors for venous thromboembolism (surgery, cancer diagnosis, hospitalization), they should be properly placed on venous thromboembolism prophylaxis.

According to this Taiwanese study, the risk of deep vein thrombosis was the highest in the first years after rheumatoid arthritis diagnosis.

The Taiwanese study focused on newly diagnosed rheumatoid arthritis, while our study used prevalent cases of rheumatoid arthritis. They were able to look at the risk by time since rheumatoid arthritis diagnosis. Overall, the mean follow-up time was quite long (over 6 years), whereas our study has over 2 years of follow-up on average.

The Taiwanese findings regarding the interaction between rheumatoid arthritis and comorbidity is interesting clinically, but it is important to note that their adjusted hazard ratio was adjusted only for age, sex, and comorbidity, which was made into a dichotomized (yes/no) variable, which may be too simple.

The Taiwanese study reported that around 7% of patients had hypertension, which seems somewhat low, given that the mean age of the cohort was 52 years. Our cohort had the same mean age and 24%-30% had hypertension. We excluded patients with cancer at baseline, and the Taiwanese study included them.

As the Taiwanese investigators write in the discussion section of their report, the lack of data on some known risk factors such as oral contraceptive use, steroids, and other drugs would lead to incomplete adjustment for confounding.

Because both studies used mainly claims data, it is important to adjust for health care use patterns to minimize surveillance bias. In other words, patients without rheumatoid arthritis may not seek medical care as much as rheumatoid arthritis patients. Physicians may behave differently when they have a patient with possible venous thromboembolism symptoms in the presence or absence of rheumatoid arthritis. My guess is that, if the Taiwanese study does further adjustment for health care use, the hazard ratio would get smaller.

Further research is needed to evaluate whether or not the additional venous thromboembolism risk in patients with rheumatoid arthritis can be modified by disease-modifying antirheumatic drugs or other factors (such as physical activity, obesity, or smoking).

Dr. SeoYoung C. Kim is assistant professor of medicine at Brigham and Women’s Hospital, Boston. Her study was funded by the National Institutes of Health. She has received research support from Pfizer and tuition support from the pharmacoepidemiology program at the Harvard School of Public Health, which is funded by Pfizer, Millennium, and ASISA.

Title
Accumulating evidence of risk
Accumulating evidence of risk

Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.

Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.

Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.

Courtesy Dr. Chia-Hung Kao
Dr. Wei-Sheng Chung

In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.

After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).

The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.

Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.

"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.

In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.

Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.

The study cohort was 77% female and had a mean age of 52 years.

The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.

Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.

Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Having rheumatoid arthritis tripled the risk for developing deep vein thrombosis and doubled the risk for pulmonary embolism in an analysis of data on 146,190 Taiwan residents.

Investigators identified 29,238 people with new diagnoses of rheumatoid arthritis in 1998-2008 in a national database with health records on Taiwan’s entire population of 23.7 million people. They extended the monitoring period for the study to the end of 2010 and compared the rheumatoid arthritis cohort with 116,952 control patients matched by sex and age in the year of diagnosis.

Expressed in person-years of follow-up, the incidence density of deep vein thrombosis was significantly higher in patients with rheumatoid arthritis (11 per 1,000 person-years), compared with the control group patients (3 per 1,000 person-years). The incidence density of pulmonary thromboembolism also was significantly higher in patients with rheumatoid arthritis compared with controls (4 vs. 2 per 1,000 person-years), Dr. Wei-Sheng Chung and his associates reported Aug. 7 in the Annals of the Rheumatic Diseases.

Courtesy Dr. Chia-Hung Kao
Dr. Wei-Sheng Chung

In all, the data included 193,753 person-years of follow-up in the rheumatoid arthritis group and 792,941 person-years of follow-up in the control group.

After adjusting for age, sex, and comorbidities, the rheumatoid arthritis group had a 3.36-fold higher chance of developing deep vein thrombosis and a 2.07-fold higher risk for developing pulmonary embolism, compared with controls, reported Dr. Chung of Taichung (Taiwan) Hospital and his colleagues (Ann. Rheum. Dis. 2013 Aug. 7 [doi:10.1136/annrheumdis-2013-203380]).

The greatest rise in risk was seen in young adults (50 years or younger) with rheumatoid arthritis, who had a nearly six-fold increased risk for deep vein thrombosis and a tripled risk for pulmonary embolism, compared with controls. The increased risk for deep vein thrombosis was seen mainly in the first 4 years after diagnosis of rheumatoid arthritis, which relied on American College of Rheumatology 1987 criteria that may have identified the disease at a later stage, the investigators suggested. The ACR and the European League Against Rheumatism (EULAR) revised their classification criteria in 2010 to focus on features at earlier stages of the disease.

Patients with rheumatoid arthritis were significantly more likely than controls to have comorbidities, including hypertension, diabetes, hyperlipidemia, heart failure, or lower leg fracture or surgery. The presence of both rheumatoid arthritis and a comorbidity multiplied the risk for thromboembolism, with a six-fold increased risk for deep vein thrombosis and a four-fold increased risk for pulmonary embolism, compared with patients with neither rheumatoid arthritis nor a comorbidity.

"Providing adequate care for patients with rheumatoid arthritis with comorbidities is an important step in preventing further development of deep vein thrombosis and pulmonary embolism. Thus, a multidisciplinary team should guide the assessment, treatment and holistic care of patients with rheumatoid arthritis," Dr. Chung and his associates concluded.

In Taiwan, an estimated 0.1% of the population has rheumatoid arthritis, which is lower than rates of 0.5%-1% in Western countries, they noted. In general, venous thromboembolism leads to death within 30 days in 11%-30% of patients, previous data show.

Two recent population-based cohort studies of patients in Sweden (JAMA 2012;308:1350-6) and in the United Kingdom (Ann. Rheum. Dis. 2013;72:1182-7) reported a doubling in risk for venous thromboembolism in people with rheumatoid arthritis. The differences in increased risk seen in the Taiwan and Western studies may be associated with racial differences, the Taiwanese investigators suggested.

The study cohort was 77% female and had a mean age of 52 years.

The findings are limited by the fact that the Taiwanese database did not include information on smoking, body mass index, physical activity, severity of rheumatoid arthritis, and use of drugs that could affect risk, including hormone replacement therapy, anticonceptive drugs, or glucocorticoids.

Chronic inflammation in patients with rheumatoid arthritis has been associated with prothrombotic factors and endothelial dysfunction in the development of atherothrombosis in prior studies.

Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

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Major finding: Having rheumatoid arthritis tripled the risk for deep vein thrombosis and doubled the risk for pulmonary embolism after controlling for age, sex, and comorbidities.

Data source: Analysis of data from a registry of all Taiwan residents that compared 29,238 people with rheumatoid arthritis and 116,952 matched control patients.

Disclosures: Dr. Chung reported having no financial disclosures. The Taiwan government and Taichung Hospital funded the study.