25 / 28
RESULTS
A total of 24,081 patients
were randomly assigned to the
celecoxib group (mean [±SD] daily
dose, 209±37 mg), the naproxen
group (852±103 mg), or the ibu-
profen group (2045±246 mg)
for a mean treatment duration of
20.3±16.0 months and a mean fol-
low-up period of 34.1±13.4 months.
During the trial, 68.8% of the patients
stopped taking the study drug, and
27.4% of the patients discontinued
follow-up. In the intention-to-treat
analyses, a primary outcome event
occurred in 188 patients in the cel-
ecoxib group (2.3%), 201 patients
in the naproxen group (2.5%), and
218 patients in the ibuprofen group
(2.7%) (hazard ratio for celecoxib vs.
naproxen, 0.93; 95% confidence
interval [CI], 0.76 to 1.13; hazard
ratio for celecoxib vs. ibuprofen,
0.85; 95% CI, 0.70 to 1.04; P<0.001
for noninferiority in both compari-
sons). In the on-treatment analysis, a
primary outcome event occurred in
134 patients in the celecoxib group
(1.7%), 144 patients in the naproxen
group (1.8%), and 155 patients in the
ibuprofen group (1.9%) (hazard ratio
for celecoxib vs. naproxen, 0.90;
95% CI, 0.71 to 1.15; hazard ratio for
celecoxib vs. ibuprofen, 0.81; 95%
CI, 0.65 to 1.02; P<0.001 for nonin-
feriority in both comparisons). The
risk of gastrointestinal events was
significantly lower with celecoxib
than with naproxen (P=0.01) or ibu-
profen (P=0.002); the risk of renal
events was significantly lower
with celecoxib than with ibuprofen
(P=0.004) but was not significantly
lower with celecoxib than with
naproxen (P=0.19).
CONCLUSIONS
At moderate doses,
celecoxib was found to be noninfe-
rior to ibuprofen or naproxen with
regard to cardiovascular safety.
Cardiovascular safety of celecoxib,
naproxen, or ibuprofen for arthri-
tis.
N Engl J Med
2016 Nov 13;[EPub
Ahead of Print], SE Nissen, ND Yeo-
mans, DH Solomon, et al
Rheumatoid arthritis
and risk of ischemic and
nonischemic heart failure
JACC: Journal of the American College of Cardiology
COMMENT
By Daniel Solomon
MD, MPH
T
he paper by Mantel and colleagues
extends our understanding of the many
effects of rheumatoid arthritis (RA) on
the heart. For over a decade, studies have
carefully described the increased risk of myo-
cardial infarction and stroke associated with
RA. Epidemiologic analyses have found that
RA confers an independent risk for ischemic
cardiovascular disease after controlling for
typical risk factors. More recent investigations
also describe abnormalities in myocardial
function with reduced ejection fraction and
possible increases in heart failure. The cur-
rent study, using data linked through Swedish
registries, demonstrates a 22% increase in
the risk of ischemic and nonischemic heart
failure.
These authors also examined subgroups of
patients with RA and found that the increase in
risk resides in those with positive rheumatoid
factor. The authors suggest that the observed
increase in heart failure is likely from a variety
of factors, including inflammation, increased
risk of traditional risk factors, and medications
used in RA such as glucocorticoids and
NSAIDs. This new publication is an important
contribution because it sets the stage for
further studies to better delineate the causes
of an increased risk for heart failure in RA with
hopes of learning more about typical heart
failure and the role of inflammation.
Dr Solomon is Professor of
Medicine and Chief of the
Section Clinical Sciences in the
Division of Rheumatology at
Brigham and Women’s Hospital.
Take-home message
•
In this retrospective study, investigators
assessed whether patients with rheu-
matoid arthritis (RA) enrolled in Swedish
patient and rheumatology registries are
at increased risk of heart failure (HF)
independent of ischemic heart disease.
They found a rapid increase in the risk
of nonischemic HF after the onset of RA.
Moreover, the association between HF
and RA severity was strongest for non-
ischemic HF.
•
The increased risk of HF for patients
with RA appears to be independent of
ischemic heart disease.
Abstract
BACKGROUND
It is unknown whether the increased
risk of heart failure (HF) in rheumatoid arthritis (RA) is
independent of ischemic heart disease (IHD).
OBJECTIVES
This study sought to investigate the rela-
tive risk of HF overall and by subtype (ischemic and
nonischemic HF) in patients with RA and to assess
the impact of RA disease factors.
METHODS
Two contemporary cohorts of RA subjects
were identified from Swedish patient and rheumatol-
ogy registries and matched 1:10 to general population
comparator subjects. A first-ever HF diagnosis (clas-
sified as ischemic HF or nonischemic HF based on
the presence of IHD) was assessed through registry
linkages. Relative risks for a history of HF before RA
onset were calculated through odds ratios. Relative
risks of incident HF in RA were calculated as haz-
ard ratios (HRs).
RESULTS
By the time of RA onset, a history of HF
was not more common in RA. In the new-onset RA
cohort, the overall HRs for subsequent HF (any type),
ischemic HF, and nonischemic HF were between 1.22
and 1.27. The risk of nonischemic HF increased rap-
idly after RA onset, in contrast to the risk of ischemic
HF. High disease activity was associated with all HF
types but was most pronounced for nonischemic
HF. In the cohort of patients with RA of any duration,
the HRs were between 1.71 and 1.88 for the different
HF subtypes.
CONCLUSIONS
Patients with RA are at increased risk
of HF that cannot be explained by their increased
risk of IHD. The increased risk of nonischemic HF
occurred early and was associated with RA severity.
Association between rheumatoid arthritis and risk
of ischemic and nonischemic heart failure
J Am Coll
Cardiol
2017 Mar 14;69(10)1275-1285, Ä Mantel, M
Holmqvist, DC Andersson, et al.
...observed increase in heart
failure is likely from a variety
of factors, including
inflammation, increased risk
of traditional risk factors...
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VOL. 1 • NO. 1 • 2017