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  • EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update R Agca,1 S C Heslinga,1 S Rollefstad,2 M Heslinga,1 I B McInnes,3 M J L Peters,4

    T K Kvien,5 M Dougados,6 H Radner,7 F Atzeni,8 J Primdahl,9,10,11 A Södergren,12

    S Wallberg Jonsson,12 J van Rompay,13 C Zabalan,14 T R Pedersen,15

    L Jacobsson,16,17 K de Vlam,18 M A Gonzalez-Gay,19 A G Semb,20 G D Kitas,21

    Y M Smulders,4 Z Szekanecz,22 N Sattar,23 D P M Symmons,24 M T Nurmohamed25

    Handling editor Hans WJ Bijlsma

    ▸ Additional material is published online only. To view please visit the journal online ( annrheumdis-2016-209775).

    For numbered affiliations see end of article.

    Correspondence to Dr Michael T Nurmohamed, Department of Rheumatology Reade, Amsterdam Rheumatology and Immunology Center, Reade & VU University Medical Center, P. O. Box 7057, Amsterdam 1007 MB, The Netherlands;

    RA, SCH, SR and MH are co-first authors.

    DPMS and MTN are senior authors.

    Received 23 April 2016 Revised 24 July 2016 Accepted 8 September 2016 Published Online First 3 October 2016

    To cite: Agca R, Heslinga SC, Rollefstad S, et al. Ann Rheum Dis 2017;76:17–28.

    ABSTRACT Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti- inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

    INTRODUCTION Cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD), in particular ankylosing spon- dylitis (AS) and psoriatic arthritis (PsA), is

    substantially elevated compared with the general population. For RA, the magnitude of this excess risk appears comparable to that reported for patients with diabetes mellitus,1–3 necessitating aggressive and targeted CVD risk management. In 2009, the European League Against Rheumatism (EULAR) task force was convened to critically appraise existing evidence on CVD risk in patients with IJD. This EULAR task force formulated 10 recommendations for the screening and identifica- tion of CVD risk factors and the implementation of CVD risk management in IJD (see online supplementary file 1).4 In view of substantial new evidence, an update of the CVD risk management recommendations was performed. In general, CVD risk management involves the

    determination of a cardiovascular risk profile of an individual patient by using values including gender, age, smoking status, blood pressure, lipid values and diabetes mellitus status. These variables are used in risk prediction algorithms such as Framingham5 and the Systematic Coronary Risk Evaluation (SCORE)6 to calculate a 10-year risk of CVD events. When this CVD risk exceeds a certain value, that is, a 10-year risk of 10% for a fatal or non-fatal CVD event (Framingham) or a 10-year risk of 5% for fatal CVD events (SCORE), lifestyle changes and treatment with lipid-lowering agents is recommended. The importance of a healthy lifestyle is emphasised for all persons, including patients at low and intermediate cardiovascular risk. Additionally, the European Society of Cardiology (ESC) guideline on CVD prevention in clinical practice also recommends CVD risk stratifi- cation for patients with hypertension.7 The initi- ation of antihypertensives depends on the grade of hypertension and total cardiovascular risk. Drug treatment is recommended for patients with grade 3 hypertension, but also grade 2 and grade 1 hyper- tension with a high CVD risk.7 Validated RA-specific CVD risk prediction models with a proven superiority over general population CVD risk prediction algorithms are currently lacking.7

    Furthermore, the existing general population risk prediction models that aid the identification of patients who would benefit from primary preven- tion of CVD have been shown to inaccurately

    Agca R, et al. Ann Rheum Dis 2017;76:17–28. doi:10.1136/annrheumdis-2016-209775 17

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  • estimate the CVD risk in RA.8 9 Therefore, in 2009 the EULAR task force advocated the use of a 1.5 multiplication factor for these risk prediction models when certain RA disease character- istics were present.4 In addition, certain commonly used vari- ables in existing CVD risk prediction algorithms are influenced by inflammation and anti-inflammatory therapy. These risk factors behave differently in patients with IJD than in the general population, necessitating clarification and practical guidelines for rheumatologists in daily clinical practice.

    For this update, a new EULAR task force reviewed all the pre- vious recommendations from 2009 on CVD risk management in IJD. New areas were addressed, including the value of imaging in the routine assessment of CVD risk.

    METHODS Task force With the approval of the EULAR Executive Committee, the convenor (MTN) and methodologist (DPMS) who guided the task force in 2009 formed a new task force with the aim of reviewing and updating the 2009 EULAR recommendations for CVD risk management in RA and other IJD (see online supplementary file 1).4 The task force comprised 26 members from 13 European countries, including 2 patient representatives, 14 rheumatologists, 2 cardiologists, 3 internists, 1 healthcare professional and 4 fellows. The entire process was conducted in accordance with the 2014 EULAR standardised operating procedures.10

    Literature search The convenor (MTN) started by formulating a list of potential research questions. These were discussed and refined during a teleconference with other members of the task force. Thereafter, the fellows (RA, SCH, SR, MH) under guidance of the convenor (MTN) and the methodologist (DPMS) compiled the search terms for a comprehensive systematic literature review to cover all the research questions. The protocol for the literature search was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (http://www. The Wiley/Cochrane Library, Pubmed/ Medline and Embase were searched from inception (by RA, SCH, MH and librarians LJS and JCFK). The Wiley/Cochrane Library was searched up to 9 February 2015, PubMed up to 10 February 2015 and Embase up to 13 February 2015. A single search was conducted embracing all aspects of the different research questions. The following search terms were used (including synonyms and closely related words) as index terms or free-text words: ‘rheumatoid arthritis’ or ‘spondyloarthritis’ and ‘cardiovascular disease’ and ‘cholesterol’ or ‘blood pressure’ or ‘smoking’ or ‘diabetes’ or ‘chronic kidney insufficiency’ or ‘sex factors’ or ‘vitamin D’ or ‘adrenal cortex hormones’ or ‘tumor necrosis factor’ or ‘anti-inflammatory agents’ or ‘inflam- mation’ or ‘carotid intima media’. The full search strategies for the Wiley/Cochrane Library, PubMed and Embase are shown in online supplementary file 2.

    All duplicates were removed from the results of the first search (figure 1). The remaining studies were screened by title

    Figure 1 Flow chart of the search and selection process. RA, rheumatoid arthritis; AS, ankylosing spondylitis; PsA, psoriatic arthritis.

    18 Agca R, et al. Ann Rheum Dis 2017;76:17–28. doi:10.1136/annrheumdis-2016-209775


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