Based on available evidence and expert consensus, a working group put together by the European Society of Cardiology (ESC) on Cardiovascular Pharmacotherapy released a position paper on lipid management in rheumatoid arthritis (RA). This report was published in European Heart Journal – Cardiovascular Pharmacotherapy.
Investigators performed a systematic review of studies focused on strategies for lipid management based on the estimation of cardiovascular risk for RA. In addition, the working group proposed a new algorithm to stratify patient risk. Opinion-based recommendations were developed to facilitate lipid-modifying therapies in RA until further evidence becomes available.
Recommendations for Lipid Assessment
The panel recommends annual lipid assessment in patients with RA with high-risk cardiovascular factors (high-risk RA), regardless of age. Reassessment of risk should be considered if patients make substantial lifestyle changes that influence lipid levels and cardiovascular risk or if they initiate treatment with disease-modifying antirheumatic drugs (DMARDs) or high-dose glucocorticoid therapy. Examination of lipid status is also recommended among patients with “low-risk RA” or whose disease activity has been reduced, regardless of age. The panel suggests lipid assessment 1 to 4 months after initiation of DMARDs and 4 to 8 weeks after initiation of treatment with interleukin-6 inhibitors, and subsequently at 6-month intervals.
Lipid monitoring should be adjusted according to the severity and treatment response. Individuals predisposed to adverse effects or with a short life expectancy may not benefit from stringent lipid management. On the other hand, patients with severe lipid abnormalities or those who experience a poor response to treatment may be screened more frequently.
In patients with RA, routine lipid monitoring should include total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total glucose concentrations, in which fasting assessment is ideal but may be performed under nonfasting conditions. If nonfasting total glucose levels are ≥2.3 mmol/L (200 mg/dL), fasting levels should be assessed.
To guide lipid-modifying therapies in RA, non-HDL-C (calculated by subtracting HDL-C from total cholesterol) is recommended as a superior marker to LDL-C as it is not influenced by food intake and high total cholesterol levels. The panel suggests that non-HDL-C is more accurate especially in patients with high total glucose and low HDL-C.
To refine risk estimation, lipoprotein(a) screening may be considered in individuals with moderate or high cardiovascular risk or with a family history of early cardiovascular disease.
Recommendations for Stratification According to Cardiovascular Risk
Investigators propose an algorithm that may be feasible for clinical practice to estimate RA-specific cardiovascular risk and guide lipid management strategies in patients with RA. The algorithm uses LDL-C as the primary treatment target but can be adapted to a non-HDL-C target. Using Systematic Coronary Risk Evaluation (age, sex, cholesterol levels, blood pressure, smoking status, and geographic region), the algorithm can be further adapted to the appropriate national risk prediction tool in which the preferred version should preferably include HDL-C.
According to the panel, low-risk RA can be defined as patients with seronegative, nonerosive RA who present without extra-articular manifestations, in long-term remission (>1 year), with well-preserved physical function, without active arthritis or high cumulative disease activity, and not receiving glucocorticoids or have a high cumulative glucocorticoid dose. Patients who do not fall under this definition can be classified as high-risk RA.
Patients with low-risk RA can be recommended to follow lipid management guidelines for the general population, but goal LDL-C levels of <3 mmol/L (115 mg/dL) should be considered in all individuals with low/moderate cardiovascular risk. Patients with high-risk RA are classified into a higher ESC risk category and therefore can be recommended to follow lower LDL-C targets than for the general population.
Because of the high occurrence of unrecognized cardiovascular disease in patients with RA, a proactive approach to diagnosing cardiovascular disease is recommended. Carotid ultrasonography to detect subclinical plaques is recommended in patients with RA as this method can be clinically meaningful across all ESC cardiovascular risk categories, particularly in moderate or high-risk RA.
Among patients with diabetes aged >40 years, the investigators recommend the use of statins; younger patients with pronounced cardiovascular risk may also benefit from receiving statins.
Although risk calculators are intended to facilitate clinical decision making, the investigators emphasize that cardiovascular risk estimation should ultimately be individualized to the patient’s overall situation, including comorbidities, laboratory results, treatment status, psychosocial factors, lifestyle, and clinical characteristics.
Recommendations for Therapeutic Interventions
Many patients with RA, especially high-risk RA, can benefit from intensified lipid management with lower LDL-C targets and an emphasis on a healthy lifestyle.
Investigators recommend that all patients with RA receive adequate lifestyle counseling and support. Lifestyle modifications may include adopting a healthy diet, increasing physical activity, achieving optimal weight, abstaining from smoking, and introducing psychosocial interventions such as stress management.
In patients with RA, aerobic exercise and resistance training can improve their lipid profiles, lower cardiovascular risk, disease activity, and functional status. Adults with RA should perform at least 150 minutes of moderate physical activity or 75 minutes of vigorous physical activity per week. Diet should be based on general population guidelines, using supplements to make up for deficiencies that cannot be corrected by diet.
If lipids cannot be managed through lifestyle, the investigators suggest pharmacologic treatment with statins. Although the optimal statin regimen for patients with RA requires further research, these drugs with profound cardioprotective and anti-inflammatory effects may be beneficial (eg, atorvastatin or rosuvastatin).
Among patients who experience an insufficient response to statins, the addition of other lipid-modifying therapies should be considered, including the LDL-C reducing drugs ezetimibe, proprotein convertase subtilisin/kexin Type 9 (PCSK9) inhibitors, and fibrates.
Other lipid abnormalities may be treated with drugs indicated to reduce total glucose and lipoprotein(a) levels and should follow general population guidelines. These drugs include statins, fibrates, ezetimibe, omega-3 fatty acids, icosapent ethyl, niacin, apheresis, novel lipid therapies such as PCSK9 inhibitors, and DMARDs.
Hollan I, Ronda N, Dessein P, et al. Lipid management in rheumatoid arthritis: a position paper of the Working Group on Cardiovascular Pharmacotherapy of the European Society of Cardiology. Eur Heart J Cardiovasc Pharmacother. 2020;6(2):104-114.