Got this in my email today. Thought it was a good thing to post in light of recent discussions.
TNF blockers may reduce cardiovascular risk associated with RA
Malmo, Sweden - In what is reportedly the first study to look at the
link between tumor necrosis factor (TNF) inhibitors and cardiovascular
events, researchers have determined that aggressive antirheumatic
therapy is cardioprotective. "We found a decreased incidence and
relative risk for the development of severe first-time
cardiovascular-disease [CVD] event when controlling for disease
severity in patients with rheumatoid arthritis [RA] treated with
TNF-blocking therapy," comment the researchers, led by Dr Lennart
Jacobsson (Malmo University Hospital, Sweden). Their work appears in
the July 2005 issue of the Journal of Rheumatology [1].
Funded by Lund University and the Swedish Rheumatism Association, the
investigators recruited patients from a regional register that included
over 90% of patients with RA started on TNF blockers in 1999 or later.
Of a total of 983 patients in the combined cohort, 531 received
treatment with etanercept (Enbrel, Amgen/Wyeth) or infliximab
(Remicade, Centocor) during the study period. The total cohort was
linked with national registers for inpatient care and cause of death.
The researchers estimated cardiovascular events in those treated with
TNF blockers vs those not treated using age- and sex-adjusted
incidence-density computations with treatment and disease-severity
markers as time-dependent covariates.
Our data suggest that overall treatment with TNF blockers in RA is safe
from a cardiovascular point of view and appears to have a protective
effect against CVD.
"Our investigation supports previous studies describing an increased
risk for cardiovascular disease in patients with RA," Jacobsson and
colleagues note. "Our data suggest that overall treatment with TNF
blockers in RA is safe from a cardiovascular point of view and appears
to have a protective effect against CVD. These findings are also
compatible with the hypothesis that inflammation is an important
pathogenetic factor in the development of CVD events."
Age- and sex- adjusted incidence of cardiovascular disease
The researchers point to a number of limitations to their study,
including the sample size, which does not allow subgrouping of
individual cardiovascular events. For example, it is possible that TNF
inhibitors may have a differential effect on arterial thromboembolic
events and heart failure. They also note that confounding by indication
or channeling may have affected the results of this study, if patients
with prevalent cardiovascular disease at baseline were less likely to
be treated with TNF blockers. However, the team did work to limit the
study to new-onset cardiovascular disease to decrease the likelihood of
differences in baseline risk.
"We found increased disability and disease severity to be predictive of
CVD in our study," Jacobsson and colleagues comment. "Further, we
observed that patients starting anti-TNF therapy had a more severe
disease and higher level of disease activity compared with a community
RA population. It is conceivable that patients who start anti-TNF
treatment, who usually have severe, refractory disease, are at a higher
baseline risk of developing CVD. We suggest that the excess risk of CVD
in such patients is reduced by aggressive antirheumatic therapy."
The group points out that the emergence of the CD4+ CD28-null T-cell
phenotype has been shown to be facilitated by TNF in vitro. These and
other immunopathologic mechanisms in RA may be involved in the
development of acute coronary syndromes and could be downregulated by
blocking TNF. "Our results underline the importance of further study of
the role of proinflammatory cytokines in CVD
Source
Jacobsson LT, Turesson C, Gulfe A, et al. Treatment with tumor necrosis
factor blockers is associated with a lower incidence of first
cardiovascular events in patients with rheumatoid arthritis. J
Rheumatol 2005; 32:1213-1218.
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