Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease, but in contrast to the well-established risk of myocardial infarction (MI), the results from studies on RA-related risk of stroke have been inconsistent. Also, we recently found an association between RA and atrial fibrillation (AF), which is an important risk factor for stroke. Most of these data, however, stem from more dated cohorts where the RA-specific treatment was less aggressive than today. Consequently, this study examined the incidence of MI, stroke and AF in a large, unselected, nationwide cohort of biologically treated RA patients.
Methods:
In Denmark, biological RA treatment is provided at no cost, but patients are required to be registered and followed in the DANBIO registry. All RA patients treated with biological agents during the period 2001-2009 were matched with 10 individuals from the general population by age and sex at the start of biological therapy. Through individual-level linkage to the National Patient Register, the National Register of Medicinal Products (national prescription database) and the National Civil Register, participants were characterized with respect to comorbidity, pharmacotherapy and socioeconomic status and subsequently monitored for the outcomes of interest (MI, stroke, or AF) until emigration, death, or December 31, 2010. Incidence rates were calculated and multivariable proportional hazard models were fitted to estimate risk of outcomes in terms of hazard ratios.
Results:
A total of 3872 RA patients and 38720 controls were included. Cohort participants were predominantly women (74%) and had a mean age of 56 years. Cardiovascular and RA-specific characteristics are listed in Table 1. The cohort was followed for a mean of 4.5 years during which 639 MIs, 867 strokes and 804 cases of AF occurred. The risk of all outcomes was significantly increased in biologically treated RA patients with a 95% excess risk of MI, 31% excess risk of stroke, and 35% excess risk of AF in the fully adjusted analysis (Table 2).
Conclusion:
In a large, nationwide and well-characterized cohort of RA patients treated with biological agents, the risk of MI was approximately two times higher than in the general population, while the excess risk of stroke and AF was less pronounced. The results indicate that despite aggressive treatment of RA the risk of major cardiovascular events is increased in these patients.
Table 1: Baseline characteristics
|
|
Biologically treated RA patients n=3872 |
Controls n=38720 |
|
Age |
56 (±13) years |
56 (±13) years |
|
Females |
2861 (74 %) |
28610 (74 %) |
|
Follow-up |
4.5 years |
4.5 years |
|
Pharmacological treatment |
|
|
|
Aspirin |
403 (10.4 %) |
3604 (9.3 %) |
|
Beta blockers |
462 (11.9 %) |
3574 (9.2 %) |
|
RAS inhibitors |
554 (14.3 %) |
5057 (13.1 %) |
|
Lipid-lowering drugs |
333 (8.6 %) |
3917 (10.1 %) |
|
NSAIDs |
2710 (70.0 %) |
8691 (22.4 %) |
|
DMARDs |
2944 (76.0 %) |
0 (0.0%) |
|
Charlson co-morbidity index |
0.06 (±0.36) |
0.06 (±0.39) |
|
Previous CV disease |
|
|
|
Myocardial infarction |
107 (2.8 %) |
704 (1.8 %) |
|
Stroke |
68 (1.8 %) |
795 (2.1 %) |
|
Atrial fibrillation |
103 (2.7 %) |
777 (2.0 %) |
|
Socioeconomic status (1=low to 4=high) |
2.51 (1.04) |
2.50 (1.13) |
|
RA-specific characteristics |
|
|
|
RA duration |
8 (3-16) years |
– |
|
HAQ score |
1.25 (0.73-1.75) |
– |
|
DAS28crp score |
5.1 (4.1-5.9) |
– |
|
CRP |
14 (7-32) mg/l |
– |
|
HAQ, Health Assessment Questionnaire; DAS, Disease activity score; RAS, Renin-angiotensin system; NSAID, Non-steroidal anti-inflammatory drug; DMARD, Disease-modifying anti-rheumatic drug; CV, cardiovascular; CRP, C-reactive protein. Numbers are means (±SD), n (%) and medians (interquartile range) as appropriate. |
||
Table 2: Risk of adverse cardiovascular events in biologically treated RA patients versus controls (reference)
|
|
Myocardial infarction |
Stroke |
Atrial Fibrillation |
|||
|
|
RA |
Controls |
RA |
Controls |
RA |
Controls |
|
Events (n) |
106 |
533 |
98 |
769 |
103 |
701 |
|
Incidence rate (events per 1000 py) |
5.7 |
2.8 |
5.2 |
4.1 |
5.7 |
3.9 |
|
Risk models |
Hazard ratios (95% CI) |
|||||
|
Unadjusted |
1.98 (1.60-2.44) |
1.31 (1.06-1.62) |
1.41 (1.14-1.73) |
|||
|
As above + co-morbidity and socioeconomic status |
2.02 (1.63-2.49) |
1.33 (1.08-1.65) |
1.42 (1.15-1.75) |
|||
|
As above + CV medication and previous CV disease* |
1.95 (1.57-2.43) |
1.31 (1.05-1.63) |
1.35 (1.09-1.68) |
|||
|
py, person-years; CI, confidence interval; CV, cardiovascular. * Covariates included individually (as outlined in Table 1). |
||||||
Disclosure:
S. A. Winther,
None;
P. R. Hansen,
None;
S. L. Kristensen,
None;
L. Dreyer,
None;
O. Ahlehoff,
None;
L. Linde,
None;
C. Torp-Pedersen,
None;
J. Lindhardsen,
None.
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