https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)30468-8.pdf

Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials

Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background
Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease.

Objectives
To quantify the benefit and harm of adding clopidogrel to standard long-term aspirin therapy for preventing cardiovascular events in people at high risk of cardiovascular disease and those with established cardiovascular disease.

Search methods
The searches have been updated: CENTRAL (Issue 3 2009), MEDLINE (2002 to September 2009) and EMBASE (2002 to September 2009).

Selection criteria
All randomized controlled trials comparing long term use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in patients with coronary disease, ischemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease were included.

Data collection and analysis
Data on mortality, non-fatal myocardial infarction, non-fatal stroke, unstable angina, heart failure, revascularizations, major and minor bleeding, and all adverse events were collected. The overall treatment effect was estimated by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel).

Main results
No new studies were identified from the updated searches. A total of two RCTs were found: the CHARISMA and the CURE study. The CURE study enrolled only patients with a recent non-ST segment elevation acute coronary syndrome. The use of clopidogrel plus aspirin, compared with placebo plus aspirin, was associated with a lower risk of cardiovascular events (OR: 0.87, 95% CI 0.81 to 0.94; P<0.01) and a higher risk of major bleeding (OR 1.34, 95% CI 1.14 to 1.57; P<0.01). Overall, we would expect 13 cardiovascular events to be prevented for every 1000 patients treated with the combination, but 6 major bleeds would be caused. In the CURE trial, for every 1000 people treated, 23 events would be avoided and 10 major bleeds would be caused. In the CHARISMA trial, for every 1000 people treated, 5 cardiovascular events would be avoided and 3 major bleeds would be caused.

Authors' conclusions
The available evidence demonstrates that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events and an increased risk of bleeding compared with aspirin alone. Only in patients with acute non-ST coronary syndrome benefits outweigh harms.

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events

Designing and scaling up integrated youth mental health care

Importance
Prior randomized trials have generally shown harm or no benefit of stenting added to medical therapy for patients with symptomatic severe intracranial atherosclerotic stenosis, but it remains uncertain as to whether refined patient selection and more experienced surgeons might result in improved outcomes.


Objective
To compare stenting plus medical therapy vs medical therapy alone in patients with symptomatic severe intracranial atherosclerotic stenosis.


Design, Setting, and Participants
Multicenter, open-label, randomized, outcome assessor-blinded trial conducted at 8 centers in China. A total of 380 patients with transient ischemic attack or nondisabling, nonperforator (defined as nonbrainstem or non-basal ganglia end artery) territory ischemic stroke attributed to severe intracranial stenosis (70%-99%) and beyond a duration of 3 weeks from the latest ischemic symptom onset were recruited between March 5, 2014, and November 10, 2016, and followed up for 3 years (final follow-up: November 10, 2019).


Interventions
Medical therapy plus stenting (n = 176) or medical therapy alone (n = 182). Medical therapy included dual-antiplatelet therapy for 90 days (single antiplatelet therapy thereafter) and stroke risk factor control.


Main Outcomes and Measures
The primary outcome was a composite of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. There were 5 secondary outcomes, including stroke in the qualifying artery territory at 2 years and 3 years as well as mortality at 3 years.


Results
Among 380 patients who were randomized, 358 were confirmed eligible (mean age, 56.3 years; 263 male [73.5%]) and 343 (95.8%) completed the trial. For the stenting plus medical therapy group vs medical therapy alone, no significant difference was found for the primary outcome of risk of stroke or death (8.0% [14/176] vs 7.2% [13/181]; difference, 0.4% [95% CI, -5.0% to 5.9%]; hazard ratio, 1.10 [95% CI, 0.52-2.35]; P = .82). Of the 5 prespecified secondary end points, none showed a significant difference including stroke in the qualifying artery territory at 2 years (9.9% [17/171] vs 9.0% [16/178]; difference, 0.7% [95% CI, -5.4% to 6.7%]; hazard ratio, 1.10 [95% CI, 0.56-2.16]; P = .80) and 3 years (11.3% [19/168] vs 11.2% [19/170]; difference, -0.2% [95% CI, -7.0% to 6.5%]; hazard ratio, 1.00 [95% CI, 0.53-1.90]; P > .99). Mortality at 3 years was 4.4% (7/160) in the stenting plus medical therapy group vs 1.3% (2/159) in the medical therapy alone group (difference, 3.2% [95% CI, -0.5% to 6.9%]; hazard ratio, 3.75 [95% CI, 0.77-18.13]; P = .08).


Conclusions and Relevance
Among patients with transient ischemic attack or ischemic stroke due to symptomatic severe intracranial atherosclerotic stenosis, the addition of percutaneous transluminal angioplasty and stenting to medical therapy, compared with medical therapy alone, resulted in no significant difference in the risk of stroke or death within 30 days or stroke in the qualifying artery territory beyond 30 days through 1 year. The findings do not support the addition of percutaneous transluminal angioplasty and stenting to medical therapy for the treatment of patients with symptomatic severe intracranial atherosclerotic stenosis.


Trial Registration
ClinicalTrials.gov Identifier: NCT01763320.

Effect of Stenting Plus Medical Therapy vs Medical Therapy Alone on Risk of Stroke and Death in Patients With Symptomatic Intracranial Stenosis: The CASSISS Randomized Clinical Trial.

Background: Antiplatelet agents are the mainstay for secondary prevention of non-cardioembolic stroke. This systematic review examined the safety and efficacy of

/pdf/aspirin-plus-clopidogrel-as-secondary-prevention-after-1lwk28c5lr.pdf

Chao Wang

Papers

Aspirin plus Clopidogrel as Secondary Prevention after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis