Professor Dai Shengming: What are the differences in the cardiovascular safety of different RA treatment drugs?

*It is only for medical professionals to read for reference.
How can RA patients reduce the occurrence of cardiovascular events? The choice of medication is critical
.

Although rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and joint destruction, in addition to joint manifestations, RA patients are often accompanied by extra-articular diseases, such as interstitial lung disease
.

In addition, RA patients are also more prone to cardiovascular disease (CVD), which not only brings a huge disease burden to patients, but also affects the quality of life and even survival rate of patients
.

According to reports, CVD is the main cause of death in RA patients [1]
.

Compared with the general population, the risk of CVD in RA patients is increased by 48% [2]
.

Why is the risk of CVD in RA patients increased? How does the use of therapeutic drugs affect the risk of CVD in RA patients? In this issue, we invite Professor Dai Shengming from Shanghai Sixth People's Hospital to answer our confusion and talk about the impact of drug management for RA patients on their CVD risk
.

What is the intrinsic relationship between RA and CVD? Why is the high incidence of CVD in RA patients? Professor Dai Shengming pointed out that CVD and RA have inherently related mechanisms, and these mechanisms interact to increase the risk of CVD in RA patients
.

Improving the understanding of the mechanism between RA and CVD will help us avoid related risk factors and reduce the risk of CVD in RA patients
.

Current research suggests that the chronic inflammation of RA itself and the enhancement of systemic/local inflammation mediated by autoantibodies are related to the occurrence of CVD.
In addition, the two have common traditional risk factors, such as smoking, diabetes, hypertension, and RA-related mechanisms Exacerbated the pathogenicity of traditional CVD risk factors [3]
.

"In patients with RA, due to the high level of inflammation in the body, it may cause abnormalities in oxidative stress, lipid metabolism, and vascular endothelial function, and may cause certain damage to the vascular structure, myocardial cells, valves, and cardiac conduction system, which may lead to RA.
increased CVD risk patients
.

"Professor Dai Shengming introduced the Road," CVD RA patients may occur including coronary heart disease, myocardial infarction, heart failure, congestive heart failure, arrhythmia and other
.

"RA treatment can not be ignored CVD risk in clinical practice The drugs used to treat RA mainly include glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), traditional synthetic anti-rheumatic drugs (csDMARDs), biological agents (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)
.

Professor Dai Shengming mentioned that the drugs used in the treatment of RA patients are also one of the factors that affect their CVD risk
.

Different therapeutic drugs have very different cardiovascular risks.
In the treatment of RA, the risk of CVD in patients should be considered, and therapeutic drugs should be selected carefully and rationally
.

"Glucocorticoids have a good effect in reducing inflammation and improving symptoms
.

However, long-term use may lead to femoral head necrosis, osteoporosis, peptic ulcers, etc
.
.

The use of hormones and NSAIDs may be related to the increased risk of CVD in RA patients
.

"Professor Dai Shengming when it comes to cardiovascular risk of NSAIDs, with reference to the early years of" Vioxx incident "- because of rofecoxib (COX-2 inhibitors) increase in long-term, large doses of heart cases The incidence of vascular events has been urgently recalled globally, which gives the majority of rheumatologists an inspiration to pay attention to their cardiovascular risks during the use of NSAIDs
.

csDMRADs is a class of drugs represented by methotrexate (MTX), which has anti-inflammatory and immunomodulatory effects
.

The use of csDMARDs has been shown to be associated with reducing the risk of CVD in patients
.

This may be related to the lower continuous exposure to NSAIDs and hormones and relatively better inflammation control when the patients are treated with csDMARDs [3]
.

bDMARDs and tsDMARDs are new drugs that have attracted much attention in the field of rheumatic immune diseases in recent years, including tumor necrosis factor-α (TNF-α) inhibitors, interleukin-6 (IL-6) receptor inhibitors, and T cell costimulation Factor modulators and JAK inhibitors
.

Its efficacy in the treatment of RA is significantly better than csDMARDs, but the cardiovascular risks are different: "TNF-α inhibitors can effectively control inflammation in RA patients, while reducing the incidence of cardiovascular events and improving atherosclerosis.
The occurrence of such cardiovascular events may aggravate the condition of patients with cardiac insufficiency
.

" Professor Dai Shengming pointed out
.

There are individual reports showing that the use of TNF-α inhibitors is associated with an increased risk of hospitalization for heart failure and increased mortality in elderly RA patients [3-4]
.

"IL-6 receptor inhibitors can also effectively control inflammation and relieve symptoms during the treatment of RA
.

" Professor Dai Shengming said, "but it may affect the synthesis of liver cells and interfere with the homeostasis of lipids and cholesterol.
This may It causes an increase in the risk of CVD and offsets its anti-inflammatory benefits to a certain extent
.

” However, related studies have shown that the effect of the IL-6 receptor inhibitor tocilizumab on lipid changes in RA patients does not necessarily translate into a major adverse cardiovascular event The increase in CVD, its impact on the risk of CVD in RA patients has not yet been determined [3]
.

JAK inhibitor is an oral small molecule targeted drug
.

JAK inhibitors can exert cardiovascular protection in RA patients by inhibiting various inflammatory pathways, down-regulating the expression of adhesion molecules, and reducing the production of oxidative substances
.

"But similar to IL-6 receptor inhibitors, JAK inhibitors can also cause changes in blood lipid metabolism, although this does not necessarily translate into an increase in major adverse cardiovascular events
.

" Professor Dai Shengming said
.

In recent years, the risk of venous thromboembolism caused by JAK inhibitors has received widespread attention.
The RA management recommendations updated in 2019 suggest that patients at high risk of thromboembolic events should use JAK inhibitors with caution [5]
.

As mentioned above, among the biological preparations for the treatment of RA, there is another type of biological preparations that target T cells.
What about its cardiovascular safety? Research evidence is coming that this biological agent can significantly reduce the risk of CVD in RA patients.
Abatacept is a T cell costimulatory signal regulator that inhibits T cell activation, and then inhibits B cell activation and antibody production, and comprehensively inhibits inflammation.
Factor release
.

Speaking of the cardiovascular safety of abatacept, Professor Dai Shengming said, "Relatively speaking, abatacept has a lower risk of cardiovascular events in patients with RA
.

" There have been a number of clinical research evidences that the heart of abatacept Vascular safety is good and can significantly reduce the risk of CVD in RA patients
.

A retrospective cohort study compared the risk of coronary heart disease when using different bDMARDs in RA patients
.

The results found that after multivariate adjustment, compared with abatacept, the risk of acute myocardial infarction (AMI) in patients who were initially treated with TNF-α inhibitors increased by 28% (Figure 1) [6].
It shows that the risk of AMI in RA patients using abatacept is lower than that of patients using TNF-α inhibitors; Figure 1: A comparison of the risk of acute myocardial infarction in RA patients using different biological agents (using abatacept as a reference value) and another One study compared the cardiovascular safety of abatacept or TNF-α inhibitors in RA patients with or without CVD
.

The results showed that compared with TNF-α inhibitors, abatacept significantly reduced the risk of CVD in RA patients, especially in RA patients with CVD at baseline [7]
.

In addition, for RA patients with diabetes, studies have also shown that abatacept has better cardiovascular safety than TNF-α inhibitors [8]
.

At the 2020 European Union Against Rheumatism (EULAR) Annual Meeting, a population-based case-control study presented by the Taiwanese research team showed that the use of abatacept is associated with a reduction in the risk of major adverse cardiovascular events (MACE) [9]
.

Regarding the management of therapeutic drugs for RA patients, Professor Dai Shengming emphasized that we must not only select drugs based on the patients' joint symptoms, but also consider the patient's comorbidity, combination medications, etc.
, and then formulate appropriate individualized treatment strategies after comprehensive evaluation
.

"If the patient responds poorly to conventional traditional treatment drugs, biological agents or targeted drugs should be added in time
.

Considering the risk of CVD in RA patients, if the patient has cardiac insufficiency, we will try to avoid using TNF-α inhibitors; if Patients who are at risk of thromboembolism or hyperlipidemia, try to avoid the use of IL-6 receptor inhibitors and JAK inhibitors
.

In short, it is necessary to consider the patient’s own comorbidities.
In terms of CVD risk, from the current clinical evidence, Abatacept is relatively safe
.

"Professor Dai Shengming pointed out
.

Finally, Professor Dai Shengming also emphasized the standardization of RA treatment
.

RA is a chronic disease, and its treatment is a systematic process
.
When
doctors formulate treatment strategies for patients, they need to fully understand the patient’s condition.
At the same time, do a good job in patient education, emphasize the continuity of medication and the standards of drug reduction and withdrawal during the treatment process
.

Only with the cooperation of doctors and patients can the disease control be better and longer
.

Summary Because of the complexity between RA and CVD The internal connection of RA patients has significantly increased the risk of cardiovascular events
.

Among them, therapeutic drugs are one of the key factors affecting the CVD risk of RA patients
.

For patients with different types of CVD risks, the applicability and safety of various therapeutic drugs Different
.

From the existing research evidence, the use of biological agents in RA patients has greater cardiovascular benefits.
Among them, abatacept can significantly reduce the risk of CVD in RA patients
.

For patients with potential cardiovascular risk factors, clinical The above choice of Abatacept is a safer choice
.

 Expert profile Professor Dai Shengming, Director of the Department of Rheumatology and Immunology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Chief Physician, and Ph.
D.
Supervisor, Deputy Chairman of the Shanghai Rheumatology Branch Member of the Chinese Association of Rheumatology, Member of the Chinese Association of Rheumatology and Immunology Members of the Rheumatology and Immunology Physician Branch of the Association of Physicians have presided over 1 National 973 Program project and 6 National Natural Science Foundation projects as the first author/corresponding author, and published more than 20 SCI papers, with a cumulative impact factor of more than 110 points as the first The completion person or the main completion person won 1 National Science and Technology Progress Award, 1 Shanghai Science and Technology Progress Award, 2 Military Medical Achievement Awards, 1 Shanghai Medical Science and Technology Award, and Shanghai City or the Army Three of the third prizes of achievement have won the military "Science and Technology Rising Star", the first prize of the "Silver Snake Award", the highest honor in Shanghai's medical and health system, the "Excellent Doctor" of Shanghai, and the "Pujiang Talent" of Shanghai.
References: [1] Rempenault C, Combe B, Barnetche T,et al.
Metabolic and cardiovascular benefits of hydroxychloroquine in patients with rheumatoid arthritis: a systematic review and meta-analysis[J].
Ann Rheum Dis,2018,77(1):98-103.
[2]Avina-Zubieta JA,Thomas J,Sadatsafavi M,et al.
Risk of incident cardiovascular events in patients with rheumatoid arthritis:a meta-analysis of observational studies[J].
Ann Rheum Dis, 2012,71(9): 1524-1529.
[3]England BR, Thiele GM, Anderson DR, et al.
Increased cardiovascular risk in rheumatoid arthritis:mechanisms and implications[J].
BMJ,2018, 361:k1036.
[4]Wang Q, Zhang M,Wang M,et al.
Triggers of Cardiovascular Diseases in Rheumatoid Arthritis[J].
Curr Probl Cardiol, 2021,100853.
[ 5]Atzeni F, Rodríguez-Carrio J,Popa CD,et al.
Cardiovascular effects of approved drugs for rheumatoid arthritis[J].
Nat Rev Rheumatol, 2021,17(5): 270-290.
[6]Zhang J,Xie F,Yun H,et al.
Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis[J].
Ann Rheum Dis,2016,75(10):1813-1818.
[7]Jin Y,Kang EH,Brill G,et al.
Cardiovascular(CV)Risk after Initiation of Abatacept versus TNF Inhibitors in Rheumatoid Arthritis Patients with and without Baseline CV Disease[J].
J Rheumatol,2018,45(9): 1240-1248.
[8]Kang EH ,Jin Y,Brill G,et al.
Comparative Cardiovascular Risk of Abatacept and Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis With and Without Diabetes Mellitus:A Multidatabase Cohort Study[J].
J Am Heart Assoc,2018,7(3):e007393.
[9]Chen HH, Liu SC, Chang YM,et al.
FACTORS ASSOCIATED WITH THE RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENT IN PATIENTS WITH RHEUMATOID ARTHRITIS: A NATIONWIDE, POPULATION-BASED,CASE-CONTROL STUDY.
Ann Rheum Dis,2020, 79 (supplement 1):273.
#THU0124 This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position#THU0124 This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position#THU0124 This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position
.