EULAR Guidelines Updated on CVD Risk Reduction in RA

Janis C. Kelly

October 17, 2016

The recognition that rheumatoid arthritis (RA) carries a cardiovascular risk as great as that for diabetes should make rheumatologists key players in overseeing cardiovascular disease (CVD) risk management for patients with RA and other inflammatory joint diseases (IJDs). This development was highlighted most recently in an update of the European League Against Rheumatism (EULAR) recommendations for CVD risk management in these patients. The 2015 to 2016 EULAR update was published online October 3 in the Annals of the Rheumatic Diseases.

The authors write, "New evidence strengthens the notion that the excess risk of CVD morbidity and mortality in patients with RA is related to both traditional and novel CVD risk factors. Novel risk factors include inflammation, presence of carotid plaques, anticitrullinated protein antibody and rheumatoid factor positivity, extra-articular RA manifestations, functional disability and hypothyroidism."

"Despite the existing knowledge, the implementation of cardiovascular risk management is, generally speaking, still very poor in daily clinical practice," senior author Michael T. Nurmohamed, MD, PhD, professor of rheumatology at the VU University Medical Center Amsterdam Rheumatology and Immunology Center, Amsterdam, in the Netherlands, told Medscape Medical News. "This update reconfirms the increased risk and that (from a cardiovascular point of view) targeting the [underlying] disease is as important as screening and treating traditional cardiovascular risk factors. The task for the rheumatologist is to get these latter steps implemented."

Dr Nurmohamed and colleagues on the EULAR steering committee updated the 2009 EULAR guidance because of "substantial new evidence" reported in the intervening years. The 26-member steering committee included two patient representatives, 14 rheumatologists, two cardiologists, three internists, a health professional, and four fellows from 13 European countries.

The working group performed systematic literature searches and categorized evidence according to standard guidelines. The group then considered 10 concept recommendations and reconsidered all of the 2009 recommendations. They updated and graded the new recommendations on strength of the underlying evidence and categorized them according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system. Task force members then voted anonymously by mail on the 10 concept recommendations and indicated level of agreement for each recommendation on a scale of 0 to 10.

Key changes include adding to "overarching principles" the recommendation that clinicians be aware of the higher risk for CVD in RA, and perhaps also in ankylosing spondylitis and psoriatic arthritis. Dr Nurmohamed said, "Formerly, this was our first recommendation. We moved this to the overarching principles, as it is not a recommendation in strict sense but more a generic principle."

Other changes include:

  • Reduce recommended screening for CVD risk in IJDs from yearly to every 5 years;

  • Use both total cholesterol and high-density lipoprotein cholesterol when using online calculators, preferably during stable disease or remission, but without requiring a fasting state;

  • In the absence of validated CVD risk stratification tools for RA, use a 1.5 multiplication for CVD risk prediction in patients with RA, even without disease-specific criteria such as disease duration of 10 or more years, rheumatoid factor or anticitrullinated protein antibody positivity, or the presence of certain extra-articular manifestations; and

  • Use of carotid ultrasound screening for asymptomatic atherosclerotic plaques in RA is optional. Dr Nurmohamed pointed out that the level of agreement was low for this recommendation, probably because of the absence of evidence supporting routine carotid ultrasound screening.

Changes also include:

  • Add regular exercise and a Mediterranean diet to smoking cessation for lifestyle recommendations;

  • Remove the 2009 recommendation for angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers as preferred treatment choices for hypertension in RA;

  • The authors relaxed some of the prior cautions about nonsteroidal anti-inflammatory drugs (NSAIDs) in RA and psoriatic arthritis, with the recommendation that naproxen seems to have the safest CVD risk profile, and diclofenac is contraindicated in patients with the listed cardiovascular risk factors — Dr Nurmohamed said, "Our former recommendation could be interpreted that we should be more cautious in 'our' populations than in the general population. That point of view has been changed, as we now feel that we do not have to be stricter than for the general population."

The authors expect the new, simpler guidance on use of a 1.5 multiplier in estimating CVD risk to make risk estimation easier and more feasible for daily practice, and also write that it reflects evidence that CVD risk is elevated even at very early stages of IJDs.

The new EULAR guideline deals in some depth with the problem of lipid modulation in IJDs. Active disease is associated with reduced lipid levels, which then rise during effective anti-inflammatory treatment, most notably with biologics such as tocilizumab. However, such treatment also improves the anti-atherogenic properties of high-density lipoprotein cholesterol. This implies that clinicians should wait until after starting disease-modifying IJD treatment to determine whether lipid-lowering therapy is needed.

In addition to general CVD risk-stratification questions such as prior CVD, tobacco use, antihypertensive use, presence of angina or angina equivalents such as chest pain, or shortness of breath (with or without exertion), Health Assessment Questionnaire score, and use of prednisone, Dr Nurmohamed advised clinicians to estimate 10-year risk during no or stable disease activity, as active disease leads to depressed lipid levels, and thus an incorrect risk estimation.

Eric Matteson, MD, chair of the Division of Rheumatology at the Mayo Clinic, Rochester, Minnesota, who was not involved in the EULAR study, told Medscape Medical News that the guidelines essentially endorse using national guidelines for risk assessment and management, as is common practice in the United States.

Dr Matteson said, "In general, the recommendations are more in line with what we know about risk. I think most of the recommendations are reasonable. In my view, however, there is still no validation of the 1.5 multiplication factor, and I am not convinced about its 'one-size-fits-all' utility. There are individual patient preferences and efficacy/safety profiles for NSAIDs, but the basic recommendation really should be focused around the knowledge that all NSAIDs confer some degree of CV risk and should be used with discretion, and at the lowest doses for the shortest time possible."

Questions included in the authors' "Research Agenda" for decreasing the CVD burden in patients with RA and other IJDs highlight the fact that the level of evidence for most of the recommendations is relatively weak. Key questions include the need to know how high CV risk is in patients with spondyloarthropathies or nonradiographic axial spondyloarthropathies compared with the general population, and the association between CVD risk and inflammation in those disorders.

Dr Nurmohamed said that he had been surprised by the paucity of evidence in three of the recommended research areas: whether there is increased prevalence of cardiac abnormalities (aortic valve dysfunction, conduction disorders) in patients with spondyloarthropathies and how this affects CVD risk, how treatment with NSAIDs affects CVD risk in IJD, and whether treatment targets for blood pressure and lipids should be different for patients with IJD than for the general population.

The authors conclude, "The 2015/2016 update of the EULAR recommendations for CVD risk management in patients with RA and other forms of IJD confirms and further extends the evidence of an increased CVD risk in the whole spectrum of IJD and reinforces the need for proper CVD risk management in these patients."

The study was funded by the EULAR. Various authors report receiving personal remuneration from BMS, Pfizer, and MSD and/or research funding, honoraria, or consultancy fees from AbbVie, Actavis, Amgen, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Epirus, Genesis, GSK, Hospira, Janssen, MSD, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz, Sanofi, and UCB. Dr Matteson has disclosed no relevant financial relationships.

Ann Rheum Dis. Published online October 3, 2016. Full text

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