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*Only for medical professionals to read and refer to Front Cardiovasc Med.
Published a review, and the Chinese expert team gave advice on safe medication! Rheumatoid arthritis (RA) can affect multiple organs/systems, and cardiovascular disease (CVD) is one of the most common comorbidities of RA
.
Compared with the general population, RA patients have a 48% increased risk of CVD and a 68% increased risk of myocardial infarction (MI).
Coincidentally, some RA treatment drugs also increase the risk of CVD
.
The team of Prof.
Zhang Liyun from Shanxi Bethune Hospital published a review on Front Cardiovasc Med.
, discussing the beneficial/harmful effects of various RA treatment drugs on cardiovascular, and gave recommendations for monitoring/risk avoidance, hoping to provide guidance for the majority of rheumatology and immunology colleagues or Learn from [1]
.
Figure 1 Screenshot of the official website Disease itself + drug effect, double CVD risk in RA patients At present, it is believed that the chronic inflammatory response of RA itself and the enhancement of systemic/local inflammation mediated by autoantibodies are related to the occurrence of CVD.
In addition, the two share a common tradition Risk factors, such as smoking, diabetes, hypertension, and RA-related mechanisms exacerbate the pathogenicity of traditional CVD risk factors [2]
.
Figure 2: Influence mechanism of inflammation on cardiovascular disease in RA patients (cited in the literature [3]) In clinical practice, the drugs used to treat RA mainly include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GC), traditional Synthetic disease-modifying antirheumatic drugs (csDMARDs), biological agents (bDMARDs), targeted synthetic DMARDs (tsDMARDs) and botanicals (commonly used in China)
.
Therefore, the drugs used in the treatment of RA patients are also one of the factors that affect their CVD risk
.
In the case of RA-induced CVD, RA therapy is a double-edged sword
.
Some drugs may reduce the incidence of cardiovascular disease in RA patients by inhibiting inflammation, improving endothelial function and insulin resistance, while some drugs may impair vascular repair mechanisms, have deleterious effects on the cardiovascular system, and increase the risk of CVD
.
Different therapeutic drugs have different cardiovascular risks.
In the treatment of RA, the risk of CVD should be considered, and the treatment drugs should be selected carefully and reasonably
.
What are the differences in cardiovascular safety among 6 types of RA drugs? 1.
NSAIDs NSAIDs are classified into non-selective NSAIDs according to their selectivity to cyclooxygenase-1 (COX-1) and COX-2 (ie, simultaneous inhibition of COX-1 and COX-2, such as ibuprofen, aspirin, etc.
) and selective COX-2 inhibitors (eg, rofecoxib and celecoxib)
.
Nonselective NSAIDs have traditionally been considered to have cardiovascular protective effects, but recent studies have found that these drugs also have potential cardiovascular risks, the CVD risk of which depends on the degree of inhibition of COX-1 and COX-2
.
The smaller the degree of inhibition of COX-1 and the greater the degree of inhibition of COX-2, the greater the risk of CVD may be
.
A network meta-analysis of seven NSAIDs (naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, and lumiracoxib) showed that rofecoxib compared with placebo The highest risk of MI was associated with the highest risk of MI, etoricoxib was associated with the highest risk of cardiovascular death, ibuprofen was associated with the highest risk of stroke, and naproxen was associated with a lower risk of CVD events
.
Therefore, NSAIDs should be used with caution in people with high cardiovascular risk, and drugs with low COX-2 inhibitory effect, such as naproxen and ibuprofen, should be used when necessary
.
Table 1: Effects of NSAIDs on cardiovascular risk and recommendations common in RA patients receiving ≥7.
5 mg prednisone for ≥6 months), dyslipidemia, insulin resistance, and type 2 diabetes
.
The multivariate analysis study showed that the risk of MI increased by 68% in RA patients receiving GC treatment.
Univariate analysis showed that the daily dose, cumulative course of treatment, and total cumulative dose were significantly associated with the increased risk of MI
.
Therefore, for patients in need of GC therapy, it is recommended to use the smallest effective dose possible and consider the duration of treatment
.
In addition, the patient's blood pressure, lipid levels, and blood sugar levels should be closely monitored, and other drugs should be given if necessary to counteract their side effects
.
Table 2: Effects of
GC on cardiovascular risk and recommendations At present, csDMRADs in the treatment of RA mainly include MTX, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine, and azathioprine.
The use of csDMARDs has been proved to be related to reducing the risk of CVD in patients .
Table 3: Effects of csDMRADs on cardiovascular risk and recommendations ), IL-1 receptor antagonists, and biologics targeting B cells and activated T cells .
The application of biological agents with different mechanisms has made the treatment methods of RA increasingly diversified and enriched the treatment options for patients .
Table 4: Effects and recommendations of bDMRADs on cardiovascular risk 5.
tsDMARDsJAK inhibitors target cytokine signaling pathways involved in the pathogenesis of RA and provide alternative treatment options for RA
.
Different cytokines transmit activation signals through the JAK signaling pathway and exhibit anticoagulant and procoagulant effects; therefore, patients with risk factors associated with thromboembolic events, such as advanced age, smoking, and history of thromboembolism, should be used with caution or withholding the use of JAK inhibitor
.
6.
Botanicals In China, in addition to NSAIDs, GCs and DMARDs, some botanicals are also used to treat RA, including Tripterygium wilfordii and total glucosides of paeony
.
Tripterygium wilfordii can improve ischemia-reperfusion injury and can be used for the treatment of RA in patients with angina pectoris and MI
.
However, patients should be warned about the side effects of Tripterygium wilfordii, including chest tightness, palpitations, and arrhythmias, and in severe cases, life-threatening events such as insufficient blood supply to the heart, a sudden drop in blood pressure, shock, or heart failure
.
Total glucosides of paeony can effectively reduce the levels of plasma total cholesterol, low-density lipoprotein cholesterol, triglyceride and very low-density lipoprotein cholesterol, and increase the concentration of high-density lipoprotein cholesterol, thereby inhibiting atherosclerosis to a certain extent
.
Overall, total glucosides of paeony have a protective effect against CVD, especially in patients with MI or insulin resistance
.
Table 5: Effects and recommendations of tsDMRADs and botanicals on cardiovascular risk In summary, different antirheumatic drugs have different effects on cardiovascular risk in RA patients, and their pros and cons are also different
.
When choosing an appropriate anti-rheumatic treatment plan, an individualized treatment plan suitable for the patient should be formulated according to the specific situation of the patient, weighing the advantages and disadvantages of different drugs, and according to the principle of optimal treatment
.
Reference [1] Baoqi Y, Dan M, Xingxing Z, Xueqing Z, Yajing W, Ke X, Liyun Z.
Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis[J].
Front Cardiovasc Med.
2022 Feb 3 ;8:812631.
doi: 10.
3389/fcvm.
2021.
812631.
PMID: 35187113; PMCID: PMC8850698.
[2]England BR, Thiele GM, Anderson DR, et al.
Increased cardiovascular risk in rheumatoid arthritis:mechanisms and implications[J].
BMJ, 2018, 361:k1036.
[3]Atzeni, Fabiola et al.
“Cardiovascular effects of approved drugs for rheumatoid arthritis.
” Nature reviews.
Rheumatology vol.
17,5 (2021): 270-290.
doi:10.
1038/s41584 -021-00593-3.
Published a review, and the Chinese expert team gave advice on safe medication! Rheumatoid arthritis (RA) can affect multiple organs/systems, and cardiovascular disease (CVD) is one of the most common comorbidities of RA
.
Compared with the general population, RA patients have a 48% increased risk of CVD and a 68% increased risk of myocardial infarction (MI).
Coincidentally, some RA treatment drugs also increase the risk of CVD
.
The team of Prof.
Zhang Liyun from Shanxi Bethune Hospital published a review on Front Cardiovasc Med.
, discussing the beneficial/harmful effects of various RA treatment drugs on cardiovascular, and gave recommendations for monitoring/risk avoidance, hoping to provide guidance for the majority of rheumatology and immunology colleagues or Learn from [1]
.
Figure 1 Screenshot of the official website Disease itself + drug effect, double CVD risk in RA patients At present, it is believed that the chronic inflammatory response of RA itself and the enhancement of systemic/local inflammation mediated by autoantibodies are related to the occurrence of CVD.
In addition, the two share a common tradition Risk factors, such as smoking, diabetes, hypertension, and RA-related mechanisms exacerbate the pathogenicity of traditional CVD risk factors [2]
.
Figure 2: Influence mechanism of inflammation on cardiovascular disease in RA patients (cited in the literature [3]) In clinical practice, the drugs used to treat RA mainly include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GC), traditional Synthetic disease-modifying antirheumatic drugs (csDMARDs), biological agents (bDMARDs), targeted synthetic DMARDs (tsDMARDs) and botanicals (commonly used in China)
.
Therefore, the drugs used in the treatment of RA patients are also one of the factors that affect their CVD risk
.
In the case of RA-induced CVD, RA therapy is a double-edged sword
.
Some drugs may reduce the incidence of cardiovascular disease in RA patients by inhibiting inflammation, improving endothelial function and insulin resistance, while some drugs may impair vascular repair mechanisms, have deleterious effects on the cardiovascular system, and increase the risk of CVD
.
Different therapeutic drugs have different cardiovascular risks.
In the treatment of RA, the risk of CVD should be considered, and the treatment drugs should be selected carefully and reasonably
.
What are the differences in cardiovascular safety among 6 types of RA drugs? 1.
NSAIDs NSAIDs are classified into non-selective NSAIDs according to their selectivity to cyclooxygenase-1 (COX-1) and COX-2 (ie, simultaneous inhibition of COX-1 and COX-2, such as ibuprofen, aspirin, etc.
) and selective COX-2 inhibitors (eg, rofecoxib and celecoxib)
.
Nonselective NSAIDs have traditionally been considered to have cardiovascular protective effects, but recent studies have found that these drugs also have potential cardiovascular risks, the CVD risk of which depends on the degree of inhibition of COX-1 and COX-2
.
The smaller the degree of inhibition of COX-1 and the greater the degree of inhibition of COX-2, the greater the risk of CVD may be
.
A network meta-analysis of seven NSAIDs (naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, and lumiracoxib) showed that rofecoxib compared with placebo The highest risk of MI was associated with the highest risk of MI, etoricoxib was associated with the highest risk of cardiovascular death, ibuprofen was associated with the highest risk of stroke, and naproxen was associated with a lower risk of CVD events
.
Therefore, NSAIDs should be used with caution in people with high cardiovascular risk, and drugs with low COX-2 inhibitory effect, such as naproxen and ibuprofen, should be used when necessary
.
Table 1: Effects of NSAIDs on cardiovascular risk and recommendations common in RA patients receiving ≥7.
5 mg prednisone for ≥6 months), dyslipidemia, insulin resistance, and type 2 diabetes
.
The multivariate analysis study showed that the risk of MI increased by 68% in RA patients receiving GC treatment.
Univariate analysis showed that the daily dose, cumulative course of treatment, and total cumulative dose were significantly associated with the increased risk of MI
.
Therefore, for patients in need of GC therapy, it is recommended to use the smallest effective dose possible and consider the duration of treatment
.
In addition, the patient's blood pressure, lipid levels, and blood sugar levels should be closely monitored, and other drugs should be given if necessary to counteract their side effects
.
Table 2: Effects of
GC on cardiovascular risk and recommendations At present, csDMRADs in the treatment of RA mainly include MTX, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine, and azathioprine.
The use of csDMARDs has been proved to be related to reducing the risk of CVD in patients .
Table 3: Effects of csDMRADs on cardiovascular risk and recommendations ), IL-1 receptor antagonists, and biologics targeting B cells and activated T cells .
The application of biological agents with different mechanisms has made the treatment methods of RA increasingly diversified and enriched the treatment options for patients .
Table 4: Effects and recommendations of bDMRADs on cardiovascular risk 5.
tsDMARDsJAK inhibitors target cytokine signaling pathways involved in the pathogenesis of RA and provide alternative treatment options for RA
.
Different cytokines transmit activation signals through the JAK signaling pathway and exhibit anticoagulant and procoagulant effects; therefore, patients with risk factors associated with thromboembolic events, such as advanced age, smoking, and history of thromboembolism, should be used with caution or withholding the use of JAK inhibitor
.
6.
Botanicals In China, in addition to NSAIDs, GCs and DMARDs, some botanicals are also used to treat RA, including Tripterygium wilfordii and total glucosides of paeony
.
Tripterygium wilfordii can improve ischemia-reperfusion injury and can be used for the treatment of RA in patients with angina pectoris and MI
.
However, patients should be warned about the side effects of Tripterygium wilfordii, including chest tightness, palpitations, and arrhythmias, and in severe cases, life-threatening events such as insufficient blood supply to the heart, a sudden drop in blood pressure, shock, or heart failure
.
Total glucosides of paeony can effectively reduce the levels of plasma total cholesterol, low-density lipoprotein cholesterol, triglyceride and very low-density lipoprotein cholesterol, and increase the concentration of high-density lipoprotein cholesterol, thereby inhibiting atherosclerosis to a certain extent
.
Overall, total glucosides of paeony have a protective effect against CVD, especially in patients with MI or insulin resistance
.
Table 5: Effects and recommendations of tsDMRADs and botanicals on cardiovascular risk In summary, different antirheumatic drugs have different effects on cardiovascular risk in RA patients, and their pros and cons are also different
.
When choosing an appropriate anti-rheumatic treatment plan, an individualized treatment plan suitable for the patient should be formulated according to the specific situation of the patient, weighing the advantages and disadvantages of different drugs, and according to the principle of optimal treatment
.
Reference [1] Baoqi Y, Dan M, Xingxing Z, Xueqing Z, Yajing W, Ke X, Liyun Z.
Effect of Anti-Rheumatic Drugs on Cardiovascular Disease Events in Rheumatoid Arthritis[J].
Front Cardiovasc Med.
2022 Feb 3 ;8:812631.
doi: 10.
3389/fcvm.
2021.
812631.
PMID: 35187113; PMCID: PMC8850698.
[2]England BR, Thiele GM, Anderson DR, et al.
Increased cardiovascular risk in rheumatoid arthritis:mechanisms and implications[J].
BMJ, 2018, 361:k1036.
[3]Atzeni, Fabiola et al.
“Cardiovascular effects of approved drugs for rheumatoid arthritis.
” Nature reviews.
Rheumatology vol.
17,5 (2021): 270-290.
doi:10.
1038/s41584 -021-00593-3.
