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In a trial in China, patients with a minor stroke or transient ischemic attack with CYP2C19 loss-of-function alleles as determined by point-of-care testing had modestly fewer second strokes with ticagrelor than with clopidogrel but also had more total bleeding events.

In this trial, patients with stroke or TIA and atherosclerosis who received a statin with or without ezetimibe were randomly assigned to an LDL cholesterol target of less than 70 mg per deciliter or to a target range of 90 to 110 mg per deciliter. At a median follow-up of 3.5 years, the incidence of a composite cardiovascular end point was 12% lower in the lower-target group than in the higher-target group. The incidence of cerebral hemorrhage did not differ significantly between the two groups.

A trial involving 11,016 patients showed that the combination of ticagrelor and aspirin after a stroke or high-risk transient ischemic attack was better than aspirin alone in preventing a stroke or death within 30 days. Severe bleeding was rare but occurred more frequently in the dual antiplatelet group.

New stroke occurred in 7% of patients who received clopidogrel–aspirin and in 9% who received only aspirin up to 72 hours after atherothrombotic stroke. Bleeding incidence was low but higher with dual antiplatelet treatment.

AbstractObjectiveTo assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA).DesignSystematic review and meta-analysis of randomised, placebo controlled trials.Data sourcesMedline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018.Eligibility criteria for selecting studies and methodsTwo reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology.ResultsThree eligible trials involving 10 447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I2=0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I2=0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I2=32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely.ConclusionsDual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.

In this international, randomized trial, patients with minor stroke or TIA who received clopidogrel plus aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone.

Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69–0·77) with a calibration slope of 0·94 (0·81–1·06) for the intracranial haemorrhage model and 0·63 (0·62–0·65) with a calibration slope of 0·97 (0·87–1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. British Heart Foundation and Stroke Association.

In this trial in nondiabetic patients with insulin resistance and a recent ischemic stroke or transient ischemic attack, pioglitazone was associated with a lower risk of stroke and MI than was placebo but with a higher risk of weight gain, edema, and bone fracture. Ischemic stroke and transient ischemic attack (TIA) affect more than 14 million persons worldwide annually. 1 , 2 Affected patients are at increased risk for future cardiovascular events, 3 , 4 and prevention of these adverse outcomes is a major goal in their care. Treatment of insulin resistance represents a potential new preventive strategy that could be added to standard care after ischemic stroke or TIA. 5 Insulin resistance is nearly universal in patients with type 2 diabetes but is also present in more than 50% of patients without diabetes who have had an ischemic stroke or a TIA. 6 The presence of insulin resistance increases . . .

People with factor XI deficiency have lower rates of ischaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose–response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA). AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose–response relationship with Multiple Comparison Procedure–Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19). Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62–77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 16·8 (90·2% CI 14·5–19·1) for placebo, 16·7 (14·8–18·6) for 25 mg milvexian once daily, 16·6 (14·8–18·3) for 25 mg twice daily, 15·6 (13·9–17·5) for 50 mg twice daily, 15·4 (13·4–17·6) for 100 mg twice daily, and 15·3 (12·8–19·7) for 200 mg twice daily. No significant dose–response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 0·99 (90·2% CI 0·91–1·05) for 25 mg once daily, 0·99 (0·87–1·11) for 25 mg twice daily, 0·93 (0·78–1·11) for 50 mg twice daily, 0·92 (0·75–1·13) for 100 mg twice daily, and 0·91 (0·72–1·26) for 200 mg twice daily. No apparent dose–response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator. Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA. Bristol Myers Squibb and Janssen Research & Development.

In this study, patients with cryptogenic stroke who were randomly assigned to undergo intensive ECG monitoring for 30 days had a higher incidence of detected atrial fibrillation (16%) than those assigned to receive standard 24-hour monitoring (3%). The prevention of stroke related to atrial fibrillation is a global public health priority. Strokes due to atrial fibrillation are common and frequently devastating (70 to 80% of patients die or become disabled 1 , 2 ), yet they are largely preventable with anticoagulant therapy (64% reduction in the risk of stroke and 25% reduction in mortality). 3 However, because atrial fibrillation is often intermittent and asymptomatic, it can be a silent risk factor that easily evades detection. 4 , 5 Since patients who have had a stroke or transient ischemic attack (TIA) due to atrial fibrillation face a high annual risk of stroke recurrence, . . .