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MindMap Gallery Major clinical trials of antithrombotic therapy for ischemic stroke
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Major clinical trials of antithrombotic therapy for ischemic stroke
There are mainly antithrombotic clinical studies in ischemic stroke. We hope that through the review and analysis of these clinical trials, we can further deepen our understanding of antithrombotic treatment in ischemic stroke and provide useful references for future clinical practice.
Edited at 2024-12-01 00:03:27
- 把時間當作朋友
這是一篇關於把時間當作朋友的心智圖，《把時間當作朋友》是一本關於時間管理和個人成長的實用指南。作者李笑來透過豐富的故事和生動的例子，教導讀者如何克服拖延、提高效率、規劃未來等實用技巧。這本書不僅適合正在為未來奮鬥的年輕人，也適合所有希望更好地管理時間、實現個人成長的人。
- Treat time as a friend
This is a mind map about treating time as a friend. "Treating Time as a Friend" is a practical guide on time management and personal growth. Author Li Xiaolai teaches readers practical skills on how to overcome procrastination, improve efficiency, and plan for the future through rich stories and vivid examples. This book is not only suitable for young people who are struggling for the future, but also for everyone who wants to better manage time and achieve personal growth.
- 高效能人士的七個習慣
這七個習慣相輔相成，共同構成了高效能人士的核心特質。透過培養這些習慣，人們可以提升自己的領導力、溝通能力、團隊協作能力和自我管理能力，從而在工作和生活中取得更大的成功。
Major clinical trials of antithrombotic therapy for ischemic stroke
- 把時間當作朋友
這是一篇關於把時間當作朋友的心智圖，《把時間當作朋友》是一本關於時間管理和個人成長的實用指南。作者李笑來透過豐富的故事和生動的例子，教導讀者如何克服拖延、提高效率、規劃未來等實用技巧。這本書不僅適合正在為未來奮鬥的年輕人，也適合所有希望更好地管理時間、實現個人成長的人。
- Treat time as a friend
This is a mind map about treating time as a friend. "Treating Time as a Friend" is a practical guide on time management and personal growth. Author Li Xiaolai teaches readers practical skills on how to overcome procrastination, improve efficiency, and plan for the future through rich stories and vivid examples. This book is not only suitable for young people who are struggling for the future, but also for everyone who wants to better manage time and achieve personal growth.
- 高效能人士的七個習慣
這七個習慣相輔相成，共同構成了高效能人士的核心特質。透過培養這些習慣，人們可以提升自己的領導力、溝通能力、團隊協作能力和自我管理能力，從而在工作和生活中取得更大的成功。
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Major clinical trials of antithrombotic therapy for ischemic stroke
CAPRIE
1996 LANCET
Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events
19,185 patients from 16 countries (Europe and the United States) involving 384 clinical centers, including recent ischemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease
Group
Clopidogrel group: 75 mg clopidogrel tablets and aspirin placebo tablets
Aspirin group: 325 mg aspirin tablets, clopidogrel placebo tablets
Average follow-up was 1.91 years
end event
Ischemic stroke: includes all types of ischemic stroke. Myocardial infarction: includes all types of myocardial infarction. Vascular death: refers to death caused by vascular causes, including ischemic stroke, myocardial infarction or other vascular causes.
Long-term use of clopidogrel is more effective than aspirin in patients with atherosclerotic vascular disease (for stroke alone, the difference is not statistically significant), and the overall safety profile is at least equivalent to that of moderate-dose aspirin.
IST
1997 LANCET
International Stroke Trial
19,435 AIS patients from 467 hospitals in 36 countries Randomized within 48 hours of symptom onset
Group
Unfractionated heparin 5000/12500IU bid
Aspirin 300mg qd Unfractionated heparin 5000IU bid
Aspirin 300mg qd Unfractionated heparin 12500IU bid
Aspirin 300mg qd
Unfractionated heparin 5000IU bid
Unfractionated heparin 12500IU bid
Do not use aspirin or heparin
14 days
end event
14d mortality rate 6-month mortality and disability rate
There were no significant fewer deaths within 14 days in the heparin-treated group, but the same proportion were dead or dependent at 6 months as in the group not receiving heparin. Fewer patients in the heparin group had recurrent ischemic strokes within 14 days, but this effect was offset by an increase in hemorrhagic strokes. There was no significant reduction in the number of deaths within 14 days in the aspirin treatment group, but there was a trend towards a reduction in the proportion of deaths or dependence within 6 months. Fewer patients in the aspirin group had a recurrence of ischemic stroke within 14 days, and there was no significant increase in the risk of hemorrhagic stroke. There is no interaction between aspirin and heparin.
Compared with placebo, aspirin reduced 14-day all-cause mortality in patients with acute cerebral infarction by 0.4% (9.0% vs 9.4%, non-significant), and reduced the 14-day death and non-fatal ischemic stroke recurrence rate by 1.1% ( 11·3% vs 12·4%, significant)
CAST
1997 LANCET
Chinese Acute Stroke Trial
21,106 AIS patients from 413 hospitals in China Get treatment within 48 hours of symptom onset
Group
Aspirin 160mg qd
placebo
4 weeks
end event
Death: Death from any cause during the 4-week treatment period. Recurrent stroke: includes fatal and non-fatal recurrent stroke, further subdivided into ischemic stroke and hemorrhagic stroke. Death or Dependence: The patient's functional status was assessed at discharge and included death, dependence (requiring assistance), and independence (fully recovered or not fully recovered but independent). Other major clinical events: such as blood transfusion or fatal extracranial hemorrhage and pulmonary embolism (clinical diagnosis).
Aspirin reduced all-cause mortality over 4 weeks by 0.6%, Reduces the risk of recurrent ischemic stroke by 0.5%
MATCH
2004 Lancet
Management of ATherothrombosis with Clopidogrel in High-risk patients
7599 patients with recent (3 months) ischemic stroke or TIA and at least one additional vascular risk factor, including previous (3 years) ischemic stroke, myocardial infarction, angina, diabetes mellitus, or symptomatic peripheral Arterial disease.
Group
Double-antibody group: Aspirin 75mg qd Clopidogrel 75mg qd
Monoclonal antibody group: aspirin 75mg qd placebo
Treatment and follow-up last 18 months
Key events
The primary endpoint was the composite of ischemic stroke, myocardial infarction, vascular death, or readmission for acute ischemic events
596 (15.7%) patients in the aspirin and clopidogrel group met the primary endpoint, compared with 636 (16.7%) patients in the clopidogrel alone group, for a relative risk reduction of 6.4%, but this difference was not significant. The risk of life-threatening bleeding events was higher in the aspirin and clopidogrel group (2.6% vs 1.3%), with an absolute risk increase of 1.3%
PROFESS
2008NEJM
The Prevention Regimen for Effectively Avoiding Second Strokes
20,332 patients with recent (3 months) ischemic stroke, Chinese participants
Group
25mg aspirin bid 200mg extended-release dipyridamole bid
75mg clopidogrel qd
Average follow-up was 2.5 years
end event
The primary endpoint was first stroke recurrence, The secondary endpoint was the composite of stroke, myocardial infarction, or vascular death
The trial did not meet predefined non-inferiority criteria but showed that ASA-ERDP and clopidogrel had similar rates of preventing recurrent stroke. There is no evidence that one of these two treatment options is better than the other.
SPS3
2012NEJM
Secondary Prevention of Small Subcortical Strokes
3020 patients with recent (6 months) symptomatic lacunar infarction confirmed by magnetic resonance imaging (MRI)
Group
Double-antibody group: 325 mg aspirin enteric-coated tablets qd, clopidogrel 75 mg qd
Monoclonal antibody group: 325 mg aspirin enteric-coated tablets qd placebo
Average follow-up was 3.4 years
end event
Primary endpoint: Recurrent stroke of any type, including ischemic stroke and intracranial hemorrhage (including subdural hematoma)
Aspirin and clopidogrel (dual antiplatelet therapy) did not significantly reduce the risk of recurrent stroke (125 strokes, 2.5% per year) compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio 0.92; 95 % confidence interval [CI], 0.72 to 1.16). Dual antiplatelet therapy did not significantly reduce the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). Dual antiplatelet therapy nearly doubled the risk of major bleeding (105 bleeds, 2.1% per year) compared with aspirin alone (56 bleeds, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P <0.001). All-cause mortality was increased in the dual antiplatelet therapy group (77 deaths in the aspirin group versus 113 deaths in the dual antiplatelet therapy group) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004) .
Among patients with recent lacunar stroke, adding clopidogrel did not significantly reduce the risk of recurrent stroke and significantly increased the risk of bleeding and death compared with aspirin alone.
CHANCE
2013NEJM
Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events
A total of 5170 patients were randomized within 24 hours of the onset of minor ischemic stroke (NIHSS ≤ 3) or high-risk TIA (ABCD2 ≥ 4) in the 114-center trial.
Group
Double antibacterial (clopidogrel-aspirin) group: received clopidogrel (300 mg loading dose, 75 mg/d maintenance dose × 90 days) aspirin (first dose 75-300 mg, decided by the attending physician; thereafter 75 mg/d, 21 Queen of Heaven deactivated)
Monoclonal antibody (aspirin monotherapy) group: only received aspirin (first dose 75-300 mg, decided by the attending physician; thereafter 75 mg/d × 90 days)
end event
Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group compared with 11.7% in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe bleeding events occurred in 7 (0.3%) in the clopidogrel-aspirin group and in 8 (0.3%) in the aspirin group (P=0.73); the incidence of hemorrhagic stroke was similar in both groups. is 0.3%.
In patients with TIA or minor stroke who can be treated within 24 hours of symptom onset, the combination of clopidogrel and aspirin reduces the risk of stroke in the first 90 days more than aspirin alone without increasing the risk of bleeding.
SOCRATES
2016NEJM
Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes
A total of 13,199 AIS or TIA patients over 40 years old came from 674 centers in 33 countries and regions around the world, including 1,175 patients from 35 hospitals in China, the country with the largest number of enrolled cases. Patients were enrolled with non-severe ischemic stroke (NIHSS ≤ 5) or high-risk TIA (ABCD ≥ 4 or symptomatic moderate to severe cerebral artery stenosis) within 24 hours of onset, and who did not receive intravenous or arterial thrombolysis. , and is not considered a cardiogenic stroke.
Group
Ticagrelor (180 mg loading dose on day 1, then 90 mg twice daily) Placebo
Aspirin (300 mg on day 1, then 100 mg qd) Placebo
90 days
end event
Time of stroke, myocardial infarction, or death within 90 days
During the 90-day treatment period, 442 of 6589 patients (6.7%) in the ticagrelor group experienced the primary endpoint event, compared with 497 of 6610 patients (7.5%) in the aspirin group (risk ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P = 0.07). Ischemic stroke occurred in 385 patients (5.8%) in the ticagrelor group and 441 patients (6.7%) in the aspirin group (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding events occurred in 0.5% of patients in the ticagrelor group and 0.6% of patients in the aspirin group, with intracranial bleeding occurring in 0.2% and 0.3% of patients, respectively, and fatal bleeding in both cases.
In trials involving patients with acute ischemic stroke or TIA, ticagrelor was not shown to be superior to aspirin in reducing the incidence of stroke, myocardial infarction, or death within 90 days.
POINT
2018NEJM
Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke
4881 patients from 269 international sites (Europe and the United States) with minor ischemic stroke (NIHSS≤3) or high-risk TIA (ABCD2≥4) within 12 hours of onset
Group
Clopidogrel group: Clopidogrel (600 mg loading dose, then 75 mg qd) Aspirin (50-325 mg qd)
Control group: aspirin placebo
90 days
end event
The primary endpoint is the risk of a major ischemic event within 90 days, defined as the composite of ischemic stroke, myocardial infarction, or death from an ischemic vascular event.
Major ischemic events occurred in 121 of 2432 patients (5.0%) who received clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) who received aspirin plus placebo (hazard ratio 0.75 ; 95% confidence interval [CI], 0.59 to 0.95; P = 0.02), with most events occurring within the first week after the initial event. Major bleeding occurred in 23 patients (0.9%) who received clopidogrel plus aspirin and in 10 patients (0.4%) who received aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02)
Among patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events at 90 days but a higher risk than those who received aspirin alone. risk of major bleeding.
THALES
NEJM 2020
Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA
11,016 patients with mild to moderate acute noncardiogenic ischemic stroke (NIHSS ≤ 5) or TIA (ABCD ≥ 6 or symptomatic moderate to severe arterial stenosis) within 24 hours of onset, and these patients did not receive thrombolysis or thrombectomy treatment. China participates
Group
Ticagrelor-aspirin group: 180 mg of ticagrelor on the first day, 90 mg twice a day from the next day; the recommended dose of aspirin on the first day is 300-325 mg (if the patient has received aspirin treatment before randomization, The recommended dose can be smaller, after that, the recommended daily dose is 75-100mg)
Placebo-Aspirin Group: Aspirin Placebo
30 days
end event
The primary outcome was the composite of stroke or death within 30 days; Secondary outcomes included the incidence of first subsequent ischemic stroke and 30-day disability. The primary safety outcome was severe bleeding
The primary outcome event occurred in 303 patients (5.5%) in the ticagrelor-aspirin group and in 362 patients (6.6%) in the aspirin group (hazard ratio, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.02). Ischemic stroke occurred in 276 patients (5.0%) in the ticagrelor-aspirin group and in 345 patients (6.3%) in the aspirin group (hazard ratio, 0.79; 95% CI, 0.68 to 0.93; P=0.004). There were no significant differences in the incidence of disability between the two groups. Serious bleeding occurred in 28 patients (0.5%) in the ticagrelor-aspirin group and in 7 patients (0.1%) in the aspirin group (P=0.001).
Ticagrelor-aspirin versus aspirin alone in patients with mild-to-moderate acute noncardiogenic ischemic stroke (NIHSS score ≤5) or TIA not receiving intravenous or endovascular thrombolysis , reduced the risk of stroke or death within 30 days, but there was no significant difference in the incidence of disability between the two groups. Ticagrelor use is associated with a higher incidence of serious bleeding.
CHANCE2
NEJM 2021
Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA
202 centers in China, involving 6412 patients with minor ischemic stroke or TIA (within 24 hours of onset) carrying CYP2C19 loss-of-function alleles
In this study, CYP2C19 loss-of-function was defined by detecting specific single nucleotide polymorphisms (SNPs) that affect the metabolic activity of the CYP2C19 enzyme. Specifically, the following three variants of the CYP2C19 gene were examined in the study: CYP2C19*2 (681G→A, rs4244285): This variant results in reduced enzyme activity. CYP2C19*3 (636G→A, rs4986893): This variant also results in reduced enzyme activity. CYP2C19*17 (−806C→T, rs12248560): This variant is associated with normal enzyme activity. Based on these genotypes, patients are classified as: “Poor metabolizers”: Patients who carry at least two 2 or 3 alleles (eg, *2/*2, *2/3, or 3/*3). “Intermediate metabolizers”: patients who carry a 2 or 3 allele (for example, *1/2 or 1/*3). Only patients carrying at least one loss-of-function allele (2 or 3) were considered CYP2C19 loss-of-function carriers and included in this study. These loss-of-function alleles will affect the metabolism of clopidogrel because clopidogrel is a prodrug and needs to be converted to its active metabolite by the CYP2C19 enzyme to exert its anti-platelet aggregation effect.
Group
Ticagrelor group: 180 mg on the first day, 90 mg each time from the next day, twice a day for 90 days
Clopidogrel group: 300 mg on the first day, 75 mg each time from the next day, for 90 days
All subjects received an initial loading dose of 75-300 mg, followed by 75 mg daily for a total of 21 days of combination therapy.
end event
The primary outcome was new stroke within 3 months and the primary safety outcome was severe or moderate bleeding within 3 months
Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and in 243 (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P= 0.008). Secondary results are in the same direction as the primary results. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 170 patients (5.3%) in the clopidogrel group, respectively. in 80 patients (2.5%).
Among Chinese patients with minor ischemic stroke or TIA who carry CYP2C19 loss-of-function alleles, the 90-day risk was slightly lower with ticagrelor than with clopidogrel. There was no difference in the risk of severe or moderate bleeding between the two treatment groups, but ticagrelor was associated with more total bleeding events.
RESCUE BT2
NEJM 2023
Efficacy and Safety of Tirofiban Compared with Aspirin in the Treatment of Acute Ischemic Stroke
This multicenter trial, conducted in China, included patients with ischemic stroke without large or medium vessel occlusion, an NIHSS score of ≥5 or above, and moderate to severe weakness in at least one limb. Eligible patients have four clinical presentations: not eligible for thrombolysis or thrombectomy and within 24 hours of the patient's last known good condition; progression of stroke symptoms after 24 to 96 hours; early neurologic deterioration after thrombolysis; or There is no improvement within 4 to 24 hours after thrombolysis.
Group
Intravenous tirofiban (initial 30 min: 0.4 μg/kg/min, then 0.1 μg/kg/min) followed by placebo for 2 days
Oral aspirin (100 mg qd) IV placebo for 2 days
All patients subsequently (44 hours after intravenous tirofiban or placebo) received oral aspirin (100 mg qd) until day 90
end event
Functional independence and quality of life scores at 90 days The primary safety endpoints were death and symptomatic intracerebral hemorrhage
A total of 606 patients were assigned to the tirofiban group and 571 patients were assigned to the aspirin group. Most patients had small infarcts, presumed to be atherosclerotic. 29.1% of patients in the tirofiban group and 22.2% of patients in the aspirin group had an mRS score of 0 or 1 at 90 days (adjusted hazard ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P=0.02). Results for secondary endpoints were often inconsistent with the results of the primary analysis. Mortality rates were similar in both groups. The incidence of symptomatic intracerebral hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group.
Intravenous tirofiban was associated with a higher likelihood of a favorable outcome compared with low-dose aspirin. The incidence of intracerebral hemorrhage was low but slightly higher with tirofiban.
TREND
2024 JAMA Neurology
The Safety and Efficacy of Tirofiban for the Prevention of NeurologicalDeterioration inAcute Ischemic Stroke
Clinical trial conducted at 10 comprehensive stroke centers in China. A total of 425 patients with acute noncardiac stroke, with NIHSS scores ranging from 4 to 20, participated. Within 24 hours of onset of illness.
Group
Tirofiban group: intravenous tirofiban (0.4 μg/kg/min for initial 30 min, then 0.1 μg/kg/min for 71.5 hours) followed by placebo. 3 days in total. Overlap aspirin in the last 4 hours (150-300 mg qd within 2 weeks of onset, then 100-300 mg qd for secondary prevention)
Aspirin group: take aspirin directly, the dosage is the same as above
Follow-up evaluation at 30 and 90 days after onset of illness
end event
The primary endpoint was early neurological deterioration (NIHSS score increase of ≥4 points) within 72 hours after randomization. The primary safety endpoint was symptomatic intracerebral hemorrhage within 72 hours of randomization.
Nine patients (4.2%) in the tirofiban group and 28 patients (13.2%) in the aspirin group experienced early neurological deterioration within 72 hours of randomization (adjusted relative risk, 0.32; 95% CI, 0.16-0.65; P=.002). No patients in the tirofiban group experienced intracerebral hemorrhage. At 90 days of follow-up, three patients (1.3%) in the tirofiban group and three patients (1.5%) in the aspirin group had died (adjusted RR, 1.15; 95% CI, 0.27-8.54; P=.63), the median (interquartile range) of modified Rankin scale scores were 1.0 (0-1.25) and 1.0 (0-2), respectively (adjusted OR, 1.28 ;95% CI, 0.90-1.83; P=.17).
Among patients with noncardiac stroke who presented within 24 hours of symptom onset, tirofiban reduced the risk of early neurological deterioration but did not increase the risk of symptomatic intracerebral hemorrhage or systemic hemorrhage.
Antithrombotic drugs can reduce mortality and recurrence rates, but not disability rates