EULAR Recommendations for the Management of Cardiovascular Risk in Patients With Rheumatic and Musculoskeletal Diseases

The European Alliance of Associations for Rheumatology (EULAR) released recommendations for the clinical management of cardiovascular (CV) risk in patients with rheumatic and musculoskeletal diseases (RMDs), including gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren syndrome (SS), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS). The full report was published in Annals of the Rheumatic Diseases.

The recommendations were developed by a EULAR task force, based on an evidence-based approach and expert consensus. The task force included 20 members from 11 European countries, including 12 rheumatologists, 2 cardiologists, 1 metabolic medicine physician, 1 health care professional, 2 patient representatives, and 2 Emerging EULAR Network members. Two conveners, along with 2 methodologists and 4 fellows, guided the task force and systemic literature review process.

An initial set of research questions on 4 major topics were formulated by 2 conveners and discussed with the task force. The topics included use of cardiovascular prediction tools; interventions targeting traditional CV risk factors; interventions targeting disease-related CV risk factors; and prevalence/incidence of cardiovascular disease (CVD).

The population, intervention, comparator, and outcome (PICO) format was used to formulate the final research questions. Two working groups (the gout, vasculitis, SSc/myositis/MCTD/SS group and the SLE and APS group) performed a comprehensive review in parallel. They searched articles from inception to March 2020 in PubMed, Embase, and the Cochrane Library databases; searches for the incidence and prevalence of CV events were extended to November 2020.

A total of 105 articles were included in the review for the gout, vasculitis, SSc, myositis, MCTD, and SS and 75 articles were included in the review for SLE and APS. The outcome was CV events rather than surrogate markers of CVD.

Results of the review were presented and discussed at a second task force meeting held virtually. Recommendations were accepted when 75% or more of the task force members voted in agreement. A final set of recommendations and 4 overarching principles were prepared.

All task force members indicated their level of agreement for each recommendation (0=no agreement at all to 10=full agreement), and these results were averaged. The recommendations and the overarching principles had a level of agreement between 8.5 and 10.

Overarching Principles

1. Clinicians should be aware of increased CV risk in patients with RMDs, including gout, vasculitis, SSc, myositis, MCTD, SS, SLE, and APS. Reduction of disease activity is likely to decrease CV risk for all RMDs.
2. Risk for CV factors must be assessed and managed by rheumatologists in collaboration with primary care providers, internists or cardiologists, and other health care providers.
3. All individuals with RMDs require regular CV risk factor screening. Risk management should include screening and strict control of CV risk factors (smoking cessation, management of blood pressure, lipids, and diabetes). Assessment of CV risk is recommended within 6 months of diagnosis and can be repeated based on individual patient characteristics and risk levels.
4. Management of CV risk in patients with RMDs is important and can include patient education and counseling on CV risk, treatment adherence, and lifestyle modifications, such as a healthy diet and regular physical activity.

Recommendations for Gout, Vasculitis, SSc, Myositis, MCTD, and SS

• A thorough assessment of traditional CV risk factors, using CV prediction tools developed for the general population, is recommended in patients with gout, vasculitis, SSc, myositis, MCTD, and SS.
• For antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, a Framingham score may underestimate the CV risk; hence, it is recommended to consider information from the European Vasculitis Society (EUVAS) model, which may supplement modifiable Framingham risk factors.
• The task force noted that remission induction and remission maintenance also reduces CV risk in patients with ANCA-associated vasculitis.
• The use of beta-blockers should be avoided in patients with SSc.
• Management of blood pressure and lipids in patients with gout, vasculitis, SSc, myositis, MCTD, and SS should follow recommendations used in the general population.
• The standard use of low-dose aspirin for primary prevention is not recommended in patients with gout, vasculitis, SSc, myositis, MCTD, and SS. Treatment with platelet inhibitors should follow recommendations used in the general population.
• The use of diuretics should be avoided in patients with gout.
• A serum uric acid level below 6 mg/dL is recommended in patients with gout to potentially lower the risk for CV events and mortality. The task force noted no preferences for a particular urate-lowering therapy with regard to CV risk.
• An optimal glucocorticoid regimen that balances risk for relapse and glucocorticoid side effects may be considered to further reduce CV risk in patients with giant-cell arteritis.

Recommendations for SLE and APS

• A thorough assessment of traditional CV risk factors and disease-related risk factors is recommended in patients with SLE and/or APS to guide risk factor modification.
• Management of blood pressure
  • In patients with SLE, a blood pressure target of less than 130/80 mm Hg should be considered. Lower levels of blood pressure are associated with lower rates of CV events.
  • In patients with lupus nephritis, angiotensin-converting enzyme ACE inhibitors or angiotensin receptor blockers (ARB) is recommended for all patients with a urine protein-to-creatinine ratio of more than 500 mg/g or arterial hypertension.
  • In patients with APS, blood pressure management should be based on recommendations used in the general population.

• Providers should follow recommendations used in the general population in the management of hyperlipidemia in patients with SLE and/or APS.
• Use of low-dose aspirin
  • Based on their individual CV risk profile, patients with SLE may be candidates for preventative strategies, including the use of low-dose aspirin.
  • Prophylactic treatment with low-dose aspirin (75-100 mg daily) is recommended in patients who are carriers of asymptomatic antiphospholipid antibodies (aPL) with a high-risk aPL profile with or without traditional risk factors.
  • In patients with SLE without a history of thrombosis or pregnancy complications, prophylactic treatment with low-dose aspirin is recommended in patients with a high-risk aPL profile, and prophylactic treatment with low-dose aspirin may be considered in patients with a low-risk aPL profile.

• The task force noted that low disease activity be maintained to reduce CV risk in patients with SLE.
• Treatment with the lowest possible corticosteroid dose is recommended for patients with SLE to reduce any potential CV adverse events.
• No specific immunosuppressive medications are recommended for patients with SLE to lower the risk for CV adverse events.
• Treatment with hydroxychloroquine (recommended for all patients unless contraindicated) should be considered to reduce the risk for CV events in patients with SLE.

The main limitation of the current recommendations is the low level of evidence due to limited available studies on many research questions. Several statements relied on expert opinion due to confounding by indication and lack of propensity adjustment in the included studies.

The task force noted, “…these recommendations will enable healthcare providers and patients to mutually engage in a long-term care pathway tailored to patients’ needs and expectations for improving [CV] health in RMDs.” They also added, “As new data accumulate, this first set of ‘best available’ evidence on cardiovascular prevention in gout, vasculitis, SSc, myositis, MCTD, SS, SLE and APS will be timely updated.”

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Drosos GC, Vedder D, Houben E, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. Published online February 2, 2022. doi:10.1136/annrheumdis-2021-221733