PracticeUpdate: Dermatology - Vol 1 - No.1 - 2017

RHEUMATOLOGY 25

Rheumatoid arthritis and risk of ischemic and nonischemic heart failure JACC: Journal of the American College of Cardiology COMMENT By Daniel Solomon MD, MPH

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

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.

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.

...observed increase in heart failure is likely from a variety of factors, including inflammation, increased risk of traditional risk factors...

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.

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Dr Solomon is Professor of Medicine and Chief of the Section Clinical Sciences in the Division of Rheumatology at Brigham and Women’s Hospital.

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VOL. 1 • NO. 1 • 2017