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*Only for medical professionals to read and refer to the NCN 2021 exciting content express, not to be missed! Antiplatelet is an important strategy for the treatment of ischemic stroke.
Looking back on the past 30 years, from the initial antiplatelet therapy with aspirin alone to the major breakthroughs made in dual antiplatelet therapy, important clinical practices at home and abroad are inseparable
.
At the 24th National Neurology Conference of the Chinese Medical Association, Professor Wang Yongjun from Beijing Tiantan Hospital, Capital Medical University, gave a wonderful report on the topic of "Research Progress in Antiplatelet Therapy for Ischemic Stroke"! Figure 1: Professor Wang Yongjun's report on the era of single antiplatelet therapy (1997-2012) Professor Wang Yongjun introduced that in 1971, the British scientist Professor John Wen was the first to discover that aspirin can prevent platelet clotting and reduce the risk of blood clots.
This discovery made Professor John Wen obtain Won the Nobel Prize in 1982
.
Subsequently, aspirin was used in research on the treatment of myocardial infarction.
Until 1997, experts and scholars in the neurological field started the study of aspirin in ischemic stroke
.
Figure 2: Professor John Wen▌ CAST study (1997): the first clinical trial of aspirin in the treatment of stroke In 1997, Oxford University in the United Kingdom initiated a randomized controlled trial CAST (Chinese acute stroke trial) study of aspirin for ischemic stroke.
20655 stroke patients from more than 100 hospitals were included, and the results showed the early treatment effect of aspirin in acute ischemic stroke
.
The results of the study were published in Lacent magazine in 1997
.
▌ IST study: Parallel study of CAST Another early large-scale clinical trial IST study of aspirin, as a parallel study of CAST, included 19435 stroke patients from 34 countries other than China, further confirming that oral aspirin can be administered within 48 hours after stroke.
Significantly reduce the mortality or disability rate of stroke at the end of the follow-up period, and reduce the recurrence of stroke.
The study was also published in the Lacent journal at the same time
.
Figure 3: Comparison of CAST and IST research Professor Wang Yongjun introduced that based on these two famous clinical studies, aspirin has been written into the guidelines of various countries since 1998, opening a new era of aspirin treatment of ischemic stroke
.
Although the effect of aspirin antiplatelet therapy is significant, there is still a clinical recurrence rate of 11%-18%.
How to further reduce the recurrence of stroke is a very important problem faced by antiplatelet therapy
.
Professor Wang Yongjun said that since 2000, a series of important double antibody studies have been done internationally, including the MATCH study in 2004, the PRoFESS study in 2008 and the SPS3 study in 2012, but unfortunately, there are three studies.
All ended in failure
.
MATCH study (2004): A total of 7,599 patients with cerebral infarction or TIA within 3 months (63% of arteriolar occlusion type + unexplained type) were enrolled in the study.
They were treated with aspirin + clopidogrel or clopidogrel alone.
Followed up for 1.
5 years
.
The results showed that the composite end point was not statistically different, and the bleeding risk of the double antibody was increased
.
PRoFESS Study (2008): The study included 1360 patients with ischemic stroke within 72 hours (59% of which were lacunar strokes) who were given aspirin + extended-release diclopyr (25 mg bid/200 mg bid) or clopirox alone Gray (75mg/day) treatment
.
Observe the 90-day functional good prognosis (mRS) and stroke recurrence rate (hemorrhagic and ischemic).
The results show that there is no significant difference in mRS and stroke recurrence (bleeding and ischemia) between the two groups, suggesting that double antibodies cannot be carried Come more anti-platelet benefits
.
SPS3 Study (2012): The study included 3020 patients with acute lacunar stroke (within 2 weeks to 6 months) and were treated with aspirin (375 mg/day) or aspirin + clopidogrel (75 mg/day), with an average follow-up of 3.
4 years
.
It was found that the double antibodies did not reduce the risk of stroke recurrence, and increased the risk of bleeding and all-cause death
.
Professor Wang Yongjun analyzed that the most important reason for the failure of the three studies is that the classification of stroke has not been carried out.
The failure of these three clinical trials has brought the international antiplatelet therapy into a long lingering period
.
The era of dual antiplatelet (2013-present) ▌ CHANCE study (2013): The Chinese study rewrites the international guidelines.
The CHANCE study included a total of 5170 patients with mild stroke or TIA.
The onset time of patients was required to be within 24 hours, and they were 40 years old and 40 years old.
Above
.
Patients were randomly assigned to aspirin + placebo treatment group, or aspirin dose + clopidogrel treatment group, and the duration of double antibody treatment was 21 days
.
The results of the study showed that patients treated with dual antibodies had a lower stroke recurrence rate, and the risk of bleeding was basically the same
.
The CHANCE study opened the door to the era of dual antibodies.
So far, international guidelines have made dual antiplatelet the first recommendation for patients with ischemic stroke.
The study was also published in the NEJM journal in 2013
.
▌ POINT study (2018): Consistent with the results of the CHANCE study The POINT study and the CHANCE study in my country have the same purpose, aiming to evaluate whether the dual antibody treatment (aspirin + clopidogrel) can be compared with monoclonal antibody for patients with new-onset mild stroke or TIA ( Aspirin) is more effective in reducing the risk of early stroke recurrence
.
The study included 4881 stroke patients from 263 centers in the world, and they were randomly assigned to the aspirin group or the aspirin+clopidogrel group, and the duration of double-antibody treatment was 90 days
.
The results showed that the double antibody significantly reduced the risk of stroke recurrence, but compared to the CHANCE study, the POINT study showed that the double antibody treatment increased the risk of severe bleeding
.
The results of the POINT study further confirmed the advantages of aspirin + clopidogrel dual antibody therapy, and the study was also published in the journal NEJM in 2018
.
▌ THALES study (2020): Ticagrelor double antibody treatment can also benefit.
The THALES study included 11016 patients with non-cardiogenic, non-severe ischemic stroke or high-risk TIA
.
The patients were randomly divided into groups within 24 hours of the onset of symptoms.
They were ticagrelor (first dose 180 mg, 90 mg bid maintenance) + aspirin (first dose 300-325 mg, 75-100 mg/d maintenance), double antibodies The treatment time is 30 days
.
The results showed that compared with aspirin alone, ticagrelor combined with aspirin can significantly reduce the 30-day risk of stroke or death in patients with TIA or mild ischemic stroke
.
The results of the THALES study provide strong evidence for ticagrelor combined with aspirin dual antiplatelet therapy.
The study will also be published in the NEJM journal in 2020
.
Figure 4: Comparison of CHANCE, POINT, and THALES studies.
Based on the results of CHANCE, POINT, and THALES, the latest European Stroke Guidelines recommends: 1.
For non-cardiac embolic light ischemic stroke in the past 24 hours (NIHSS score) For patients with a score of 3 or less) or high-risk TIA (ABCD2 score of 4 or more), we recommend the use of aspirin + clopidogrel for 21 days of dual antiplatelet therapy, followed by antiplatelet monotherapy
.
(Quality of Evidence: High, Strength of Recommendation: Strong) 2.
For non-cardiogenic mild to moderate ischemic stroke (NIHSS score 5 or less) or high TIA (ABCD2 score of 6 or more or other) in the past 24 hours For people with high-risk characteristics), we recommend a 30-day dual antiplatelet therapy with aspirin and ticagrelor, followed by antiplatelet monotherapy
.
(Quality of Evidence: Medium, Strength of Recommendation: Weak) Figure 5: European stroke guidelines focus on differences in Chinese genotypes-Professor Yongjun Wang from the CHANCE-2 study introduced that the results of the CHANCE subgroup study showed that 58.
8% of the Chinese population is a carrier of CYP2C19 alleles A retrospective analysis of the CHANCE study population using pharmacogenomics methods found that the risk of recurrence in patients with the CYP2C19 functional defect gene was significantly higher than that in non-carriers
.
Therefore, the individualized antiplatelet therapy of CYP2C19 gene mutation is of great significance for patients with mild stroke
.
The CHANCE-2 study uses the GMEX system to quickly detect CYP2C19 gene polymorphisms to ensure the smooth progress of the study
.
At present, the CHANCE-2 study has been successfully completed, and the results will be published in the New England Journal shortly.
We look forward to it together! Figure 6: Residual risk of CHANCE-2 study protocol: based on multiomics of stroke Figure 7: Analysis of residual risk of stroke Professor Wang Yongjun introduced that the main purpose of treatment of ischemic stroke is to reduce the disability rate, reduce the mortality rate, and reduce the recurrence rate However, as far as current methods are concerned, there is still a certain risk of death and recurrence.
We call this part of the risk the residual risk of stroke
.
Multi-omics assays include genome, epigenetics, transcriptome, proteome, metabolome, intestinal microbiome, imaging panel, etc.
Based on multi-omics data analysis to explore the targets of stroke intervention, and provide for the reduction of residual risk Possibly, it is also a new direction for stroke treatment in the future
.
Looking back on the past 30 years, from the initial antiplatelet therapy with aspirin alone to the major breakthroughs made in dual antiplatelet therapy, important clinical practices at home and abroad are inseparable
.
At the 24th National Neurology Conference of the Chinese Medical Association, Professor Wang Yongjun from Beijing Tiantan Hospital, Capital Medical University, gave a wonderful report on the topic of "Research Progress in Antiplatelet Therapy for Ischemic Stroke"! Figure 1: Professor Wang Yongjun's report on the era of single antiplatelet therapy (1997-2012) Professor Wang Yongjun introduced that in 1971, the British scientist Professor John Wen was the first to discover that aspirin can prevent platelet clotting and reduce the risk of blood clots.
This discovery made Professor John Wen obtain Won the Nobel Prize in 1982
.
Subsequently, aspirin was used in research on the treatment of myocardial infarction.
Until 1997, experts and scholars in the neurological field started the study of aspirin in ischemic stroke
.
Figure 2: Professor John Wen▌ CAST study (1997): the first clinical trial of aspirin in the treatment of stroke In 1997, Oxford University in the United Kingdom initiated a randomized controlled trial CAST (Chinese acute stroke trial) study of aspirin for ischemic stroke.
20655 stroke patients from more than 100 hospitals were included, and the results showed the early treatment effect of aspirin in acute ischemic stroke
.
The results of the study were published in Lacent magazine in 1997
.
▌ IST study: Parallel study of CAST Another early large-scale clinical trial IST study of aspirin, as a parallel study of CAST, included 19435 stroke patients from 34 countries other than China, further confirming that oral aspirin can be administered within 48 hours after stroke.
Significantly reduce the mortality or disability rate of stroke at the end of the follow-up period, and reduce the recurrence of stroke.
The study was also published in the Lacent journal at the same time
.
Figure 3: Comparison of CAST and IST research Professor Wang Yongjun introduced that based on these two famous clinical studies, aspirin has been written into the guidelines of various countries since 1998, opening a new era of aspirin treatment of ischemic stroke
.
Although the effect of aspirin antiplatelet therapy is significant, there is still a clinical recurrence rate of 11%-18%.
How to further reduce the recurrence of stroke is a very important problem faced by antiplatelet therapy
.
Professor Wang Yongjun said that since 2000, a series of important double antibody studies have been done internationally, including the MATCH study in 2004, the PRoFESS study in 2008 and the SPS3 study in 2012, but unfortunately, there are three studies.
All ended in failure
.
MATCH study (2004): A total of 7,599 patients with cerebral infarction or TIA within 3 months (63% of arteriolar occlusion type + unexplained type) were enrolled in the study.
They were treated with aspirin + clopidogrel or clopidogrel alone.
Followed up for 1.
5 years
.
The results showed that the composite end point was not statistically different, and the bleeding risk of the double antibody was increased
.
PRoFESS Study (2008): The study included 1360 patients with ischemic stroke within 72 hours (59% of which were lacunar strokes) who were given aspirin + extended-release diclopyr (25 mg bid/200 mg bid) or clopirox alone Gray (75mg/day) treatment
.
Observe the 90-day functional good prognosis (mRS) and stroke recurrence rate (hemorrhagic and ischemic).
The results show that there is no significant difference in mRS and stroke recurrence (bleeding and ischemia) between the two groups, suggesting that double antibodies cannot be carried Come more anti-platelet benefits
.
SPS3 Study (2012): The study included 3020 patients with acute lacunar stroke (within 2 weeks to 6 months) and were treated with aspirin (375 mg/day) or aspirin + clopidogrel (75 mg/day), with an average follow-up of 3.
4 years
.
It was found that the double antibodies did not reduce the risk of stroke recurrence, and increased the risk of bleeding and all-cause death
.
Professor Wang Yongjun analyzed that the most important reason for the failure of the three studies is that the classification of stroke has not been carried out.
The failure of these three clinical trials has brought the international antiplatelet therapy into a long lingering period
.
The era of dual antiplatelet (2013-present) ▌ CHANCE study (2013): The Chinese study rewrites the international guidelines.
The CHANCE study included a total of 5170 patients with mild stroke or TIA.
The onset time of patients was required to be within 24 hours, and they were 40 years old and 40 years old.
Above
.
Patients were randomly assigned to aspirin + placebo treatment group, or aspirin dose + clopidogrel treatment group, and the duration of double antibody treatment was 21 days
.
The results of the study showed that patients treated with dual antibodies had a lower stroke recurrence rate, and the risk of bleeding was basically the same
.
The CHANCE study opened the door to the era of dual antibodies.
So far, international guidelines have made dual antiplatelet the first recommendation for patients with ischemic stroke.
The study was also published in the NEJM journal in 2013
.
▌ POINT study (2018): Consistent with the results of the CHANCE study The POINT study and the CHANCE study in my country have the same purpose, aiming to evaluate whether the dual antibody treatment (aspirin + clopidogrel) can be compared with monoclonal antibody for patients with new-onset mild stroke or TIA ( Aspirin) is more effective in reducing the risk of early stroke recurrence
.
The study included 4881 stroke patients from 263 centers in the world, and they were randomly assigned to the aspirin group or the aspirin+clopidogrel group, and the duration of double-antibody treatment was 90 days
.
The results showed that the double antibody significantly reduced the risk of stroke recurrence, but compared to the CHANCE study, the POINT study showed that the double antibody treatment increased the risk of severe bleeding
.
The results of the POINT study further confirmed the advantages of aspirin + clopidogrel dual antibody therapy, and the study was also published in the journal NEJM in 2018
.
▌ THALES study (2020): Ticagrelor double antibody treatment can also benefit.
The THALES study included 11016 patients with non-cardiogenic, non-severe ischemic stroke or high-risk TIA
.
The patients were randomly divided into groups within 24 hours of the onset of symptoms.
They were ticagrelor (first dose 180 mg, 90 mg bid maintenance) + aspirin (first dose 300-325 mg, 75-100 mg/d maintenance), double antibodies The treatment time is 30 days
.
The results showed that compared with aspirin alone, ticagrelor combined with aspirin can significantly reduce the 30-day risk of stroke or death in patients with TIA or mild ischemic stroke
.
The results of the THALES study provide strong evidence for ticagrelor combined with aspirin dual antiplatelet therapy.
The study will also be published in the NEJM journal in 2020
.
Figure 4: Comparison of CHANCE, POINT, and THALES studies.
Based on the results of CHANCE, POINT, and THALES, the latest European Stroke Guidelines recommends: 1.
For non-cardiac embolic light ischemic stroke in the past 24 hours (NIHSS score) For patients with a score of 3 or less) or high-risk TIA (ABCD2 score of 4 or more), we recommend the use of aspirin + clopidogrel for 21 days of dual antiplatelet therapy, followed by antiplatelet monotherapy
.
(Quality of Evidence: High, Strength of Recommendation: Strong) 2.
For non-cardiogenic mild to moderate ischemic stroke (NIHSS score 5 or less) or high TIA (ABCD2 score of 6 or more or other) in the past 24 hours For people with high-risk characteristics), we recommend a 30-day dual antiplatelet therapy with aspirin and ticagrelor, followed by antiplatelet monotherapy
.
(Quality of Evidence: Medium, Strength of Recommendation: Weak) Figure 5: European stroke guidelines focus on differences in Chinese genotypes-Professor Yongjun Wang from the CHANCE-2 study introduced that the results of the CHANCE subgroup study showed that 58.
8% of the Chinese population is a carrier of CYP2C19 alleles A retrospective analysis of the CHANCE study population using pharmacogenomics methods found that the risk of recurrence in patients with the CYP2C19 functional defect gene was significantly higher than that in non-carriers
.
Therefore, the individualized antiplatelet therapy of CYP2C19 gene mutation is of great significance for patients with mild stroke
.
The CHANCE-2 study uses the GMEX system to quickly detect CYP2C19 gene polymorphisms to ensure the smooth progress of the study
.
At present, the CHANCE-2 study has been successfully completed, and the results will be published in the New England Journal shortly.
We look forward to it together! Figure 6: Residual risk of CHANCE-2 study protocol: based on multiomics of stroke Figure 7: Analysis of residual risk of stroke Professor Wang Yongjun introduced that the main purpose of treatment of ischemic stroke is to reduce the disability rate, reduce the mortality rate, and reduce the recurrence rate However, as far as current methods are concerned, there is still a certain risk of death and recurrence.
We call this part of the risk the residual risk of stroke
.
Multi-omics assays include genome, epigenetics, transcriptome, proteome, metabolome, intestinal microbiome, imaging panel, etc.
Based on multi-omics data analysis to explore the targets of stroke intervention, and provide for the reduction of residual risk Possibly, it is also a new direction for stroke treatment in the future
.
