Comparative effectiveness of combined antiplatelet treatments in acute minor ischaemic stroke

BackgroundNo study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel–aspirin) versus clopidogrel–aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke.MethodsWe identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel–aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months.ResultsAmong 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel–aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel–aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel–aspirin group than in the other combination group (weighted HR: 0.82 (0.59–1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76–1.44)) or other combination group and the 3-month primary outcome.ConclusionOther combined antiplatelet treatment, compared with aspirin alone or clopidogrel–aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel–aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed.

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Abstract 104: Disability After Minor Stroke and TIA in the POINT Trial

Stroke ◽

10.1161/str.51.suppl_1.104 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Brett L Cucchiara ◽

Jordan Elm ◽

J Donald Easton ◽

Shelagh Coutts ◽

Joshua Willey ◽

...

Keyword(s):

Ischemic Stroke ◽

Adverse Events ◽

Antiplatelet Therapy ◽

Primary Outcome ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Primary Outcome Measure ◽

Minor Stroke ◽

Serious Adverse Events ◽

Index Event

Background and Purpose: To assess the effect of combination antiplatelet therapy with aspirin and clopidogrel versus aspirin alone on disability following TIA or minor stroke and to identify factors associated with disability. Methods: The POINT trial randomized patients with TIA or minor stroke (NIHSS≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, MI, or vascular death. We performed a post-hoc exploratory analysis to examine the effect of treatment on overall disability (defined as mRS>1) at 90 days as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results: At 90 days, 188/1964 (9.6%) of patients enrolled with TIA and 471/2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% vs. 14.3%, OR 0.97, 95%CI 0.82-1.14, p=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% vs. 4.0%, OR 0.73, 95%CI 0.53-1.01, p=0.06), and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% vs. 7.4%, OR 0.78, 95% CI 0.62-0.99, p=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% vs. 6.0%, OR 0.74 95% CI 0.57-0.96, p=0.02). In multivariate analysis of patients enrolled with TIA, disability was significantly associated with age, subsequent ischemic stroke, serious adverse events, and major bleeding. In patients enrolled with stroke, disability was associated with female sex, hypertension, diabetes, NIHSS score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events. Conclusions: In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, dual antiplatelet therapy might reduce stroke-related disability.

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237 Systematic Review of Fibrinogen and Risk of Recurrent Stroke and Vascular Events after Ischaemic Stroke or Transient Ischaemic Attack (TIA)

Age and Ageing ◽

10.1093/ageing/afz102.56 ◽

2019 ◽

Vol 48 (Supplement_3) ◽

pp. iii1-iii16

Author(s):

John J McCabe ◽

Eimear O'Reilly ◽

Sarah Coveney ◽

Ronan Collins ◽

Simon Cronin ◽

...

Keyword(s):

Risk Factors ◽

Ischaemic Stroke ◽

Transient Ischaemic Attack ◽

Prognostic Value ◽

Recurrent Stroke ◽

Multivariable Analysis ◽

Positive Association ◽

Case Control Studies ◽

Vascular Events ◽

Ischaemic Attack

Abstract Background Inflammation is thought to play an important role in atherosclerotic stroke mechanisms. There is growing interest in the prognostic role of inflammatory biomarkers as risk factors for recurrent vascular events, after ischaemic stroke or transient ischaemic attack (TIA). Elevated fibrinogen levels are independently-associated with the risk of first-ever stroke. However, the prognostic value of fibrinogen, after ischaemic cerebrovascular events is uncertain. Methods We searched EMBASE and Ovid Medline, from 1970-January 2019, for any study that measured Fibrinogen after stroke or TIA, and related it to the risk of recurrent stroke or recurrent vascular events. All records were assessed by 2 independent reviewers. Any disagreements between authors regarding eligibility were resolved by consensus. Results We identified 2,520 publications, of which, 15 articles from 16 individual studies were eligible (11 observational cohorts, 3 cohort studies within randomized control trials, 2 case-control studies). The sample size for recurrent stroke and recurrent vascular events was 9,963 and 7,381 patients, in 11 and 10 studies, respectively. The time from event to phlebotomy was <7 days in 5, 7-90 days in 6, and >90 days in 5 studies, respectively. There was marked heterogeneity in statistical methodologies employed to examine the relationship between fibrinogen and outcomes, which did not allow valid meta-analysis (above/below specified threshold (n=4), differences in means/medians (n=5), risk per unit increase (n=1), per standard deviation (n=3), per quartile (n=1), per decile (n=1) or not specified (n=1)). 4 studies adjusted for all conventional vascular risk factors (age, smoking, diabetes, hypercholesterolaemia/statin use, and hypertension). 2 of 11 studies found a positive association with recurrent stroke. 5 of 10 studies found a positive association with recurrent vascular events. Conclusion The prognostic value of Fibrinogen after stroke or TIA remains unclear. Standardised methods and fully-adjusted multivariable analysis are needed in future prognostic studies.

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Concurrent intracranial and extracranial artery stenosis and the prognosis of transient ischaemic symptoms or imaging-negative ischaemic stroke

Stroke and Vascular Neurology ◽

10.1136/svn-2020-000377 ◽

2020 ◽

pp. svn-2020-000377

Author(s):

Yue Suo ◽

Jing Jing ◽

Yuesong Pan ◽

Weiqi Chen ◽

Hongyu Zhou ◽

...

Keyword(s):

Ischaemic Stroke ◽

Cox Regression ◽

Recurrent Stroke ◽

Time Interval ◽

Symptom Duration ◽

Large Artery ◽

Imaging Data ◽

Vascular Events ◽

Acute Infarction ◽

Atherosclerotic Stenosis

Background and purposeTransient ischaemic attack (TIA), transient symptoms with infarction (TSI) and diffusion-weighted imaging (DWI)-negative acute ischaemic stroke (AIS) share similar aetiologies but are considered to have a rather benign prognosis. We intended to investigate the association between intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and the prognosis of patients with TIA, TSI and DWI-negative AIS.MethodsClinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study, according to symptom duration, acute infarction on DWI and discharge diagnosis. Based on the severity and location of arterial atherosclerosis, we categorised the study population into four groups: no or <50% ICAS and no ECAS; ≥50% ICAS but no ECAS; no or <50% ICAS with ECAS; and concurrent ≥50% ICAS and ECAS. Using multivariable Cox regression models, we analysed the relationship between the severity and distribution of large artery atherosclerosis and the prognosis of TIA, TSI and DWI-negative AIS.ResultsA total of 806 patients were included, 67.3% of whom were male. The median age of the study participants was 63 years. Patients in the concurrent ≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate (adjusted HR 3.4 (95% CI 1.15 to 10.04), p=0.027) and a higher risk of composite vascular events (adjusted HR 3.82 (95% CI 1.50 to 9.72), p=0.005).ConclusionsConcurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events. Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS. Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.

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Association between annual household income and adverse outcomes in patients who had ischaemic stroke

Journal of Epidemiology & Community Health ◽

10.1136/jech-2021-216481 ◽

2021 ◽

pp. jech-2021-216481

Author(s):

Yuhan Zang ◽

Zhengbao Zhu ◽

Mengyao Shi ◽

Aili Wang ◽

Xuewei Xie ◽

...

Keyword(s):

Ischaemic Stroke ◽

Household Income ◽

Primary Outcome ◽

Meta Analysis ◽

Income Level ◽

Annual Household Income ◽

Vascular Events ◽

Income Per Capita ◽

Link Type ◽

Per Capita

Background and purposeThe association between annual household income and prognosis of ischaemic stroke remains debatable. We aimed to prospectively investigate the relationship between annual household income and prognosis at 3 months after ischaemic stroke.MethodsWe included 3975 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. All participants were categorised into three groups according to annual household income per capita: <¥10 000 (Chinese Yuan Renminbi (RMB)), ¥10 000–19 999 and ≥¥20 000. The primary outcome was a composite outcome of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset, and secondary outcomes included major disability, death, and vascular events. A meta-analysis was conducted to incorporate the results of the current study and previous studies on the association of income level with outcomes after stroke.ResultsWithin 3 months after ischaemic stroke, 1002 participants (25.20%) experienced primary outcome (880 major disabilities and 122 deaths). After multivariate adjustment, low annual household income level was associated with increased risk of the primary outcome (OR 1.60; 95% CI: 1.12 to 2.31; Ptrend=0.034) when two extreme groups were compared. The meta-analysis confirmed the significant association between income level and death or major disability after stroke (pooled relative risk for lowest vs highest income level, 1.31 (95% CI: 1.18 to 1.45)).ConclusionsLow annual household income per capita was significantly associated with increased risks of adverse clinical outcomes at 3 months after ischaemic stroke, independently of established risk factors. Further studies from other samples are needed to replicate our findings due to a reason for excluding some patients who had a severe stroke in this study.Trial registration numberClinicalTrials.gov (http://wwwclinicaltrialsgov) Registry (NCT01840072).

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Selecting an optimal antiplatelet agent for secondary stroke prevention

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000842 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000842

Author(s):

Karen C. Albright ◽

Virginia J. Howard ◽

George Howard

Keyword(s):

Stroke Prevention ◽

Extended Release ◽

Primary Outcome ◽

Recurrent Stroke ◽

Antiplatelet Agent ◽

Secondary Stroke Prevention ◽

Vascular Events ◽

Randomized Controlled ◽

Participant Selection ◽

Selection Of

Four seminal randomized controlled trials (RCTs) have investigated aspirin, aspirin plus extended release dipyridamole, and clopidogrel for the prevention of recurrent vascular events. Despite studying over 32,000 stroke patients in these trials, the decision which antiplatelet agent to select for secondary stroke prevention remains controversial. Attempts to translate the results of these RCTs into clinical practice are complicated by each trial’s selection of participants and choice of primary outcome. Herein, we argue that by examining RCT results with participant selection limited to patients with ischemic stroke or TIA and by focusing on recurrent stroke as our outcome, we can use the standard epidemiology two-by-two table to assist in selecting an antiplatelet agent for secondary stroke prevention.

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Long-term risk of vascular events after peripheral bypass surgery

Thrombosis and Haemostasis ◽

10.1160/th11-12-0844 ◽

2012 ◽

Vol 108 (09) ◽

pp. 543-553 ◽

Cited By ~ 5

Author(s):

Marco J. D. Tangelder ◽

James A. Lawson ◽

Frans L. Moll ◽

Ale Algra ◽

Eline S. Van Hattum

Keyword(s):

Bypass Surgery ◽

Primary Outcome ◽

Oral Anticoagulants ◽

Critical Limb Ischaemia ◽

Individual Risk ◽

Vascular Events ◽

Peripheral Bypass ◽

Vascular Death ◽

Outcome Event

SummaryPatients with peripheral arterial disease (PAD) are at high risk of major ischaemic events. Long-term data of all major ischaemic events in PAD patients are scarce and outdated, especially for patients with severe PAD requiring bypass surgery. Our objective was to define their longterm prognosis and develop a prediction model which quantifies this risk up to a decade after surgery. We conducted a retrospective cohort study in patients from the Dutch Bypass Oral anticoagulants or Aspirin (BOA) Study; a multicentre randomised trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery. The primary outcome was the composite event of nonfatal myocardial infarction, non-fatal ischaemic stroke, major amputation, and vascular death. Cumulative risks were assessed by Kaplan-Meier analysis and independent determinants by multivariable Cox regression models. From 1995 until 2009, 482 patients were followed for a median period of 7.8 years. Follow-up was complete in 94%. Overall 60% of patients experienced a primary outcome event, of which the majority was a vascular death (30%), followed by major amputations (12%). The primary cause of vascular death was a cardiovascular event (29%), whereas the minority was due to complications directly related to PAD (6%). Within five years after bypass surgery vascular death occurred in about a quarter of patients and within 10 years in nearly half of patients. This was double the rate as for non-vascular death. The primary outcome event occurred in over a third and over half of patients in 5 and 10 years after bypass surgery, respectively. From four independent determinants for the primary outcome event: age, diabetes, critical limb ischaemia, and prior vascular interventions, we developed a risk chart, which systematically classifies the 10-year risks of the primary outcome event, ranging from 25% to 85%. This study provided a detailed insight in the course of PAD long after peripheral bypass surgery and enables individual risk assessment of major fatal and non-fatal ischaemic events by means of cumulative incidences and a risk chart.

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Long-term mortality and recurrent vascular events in lacunar versus non-lacunar ischaemic stroke: A cohort study

European Stroke Journal ◽

10.1177/23969873211062019 ◽

2021 ◽

pp. 239698732110620

Author(s):

Suzanne Portegijs ◽

Ariel Y Ong ◽

Nynke Halbesma ◽

Aidan Hutchison ◽

Cathie LM Sudlow ◽

...

Keyword(s):

Cohort Study ◽

Ischaemic Stroke ◽

Cox Regression ◽

Small Vessel Disease ◽

Recurrent Stroke ◽

Vascular Events ◽

All Cause Mortality ◽

One Year ◽

Long Term Mortality

Introduction Studies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings, with limited data on myocardial infarction (MI). We investigated whether long-term mortality, recurrent stroke and MI risks differ in people with versus without lacunar/SVD ischaemic stroke. Patients and methods We included first-ever strokes from a hospital-based stroke cohort study recruited in 2002–2005. We compared risks of death, recurrent stroke and MI during follow-up among lacunar/SVD versus other ischaemic stroke subtypes using Cox regression, adjusting for confounding factors. Results We included 812 participants, 283 with lacunar/SVD ischaemic stroke and 529 with other stroke. During a median of 9.2 years (interquartile range 3.1–11.8), there were 519 deaths, 181 recurrent strokes and 79 MIs. Lacunar/SVD stroke was associated with lower mortality (adjusted HR 0.79, 95% CI 0.65 to 0.95), largely due to markedly lower all-cause mortality in the first year. From one year onwards this difference attenuated, with all-cause mortality only slightly and not statistically significantly lower in the lacunar/SVD group (0.86, 95% CI 0.70 to 1.05). There was no clear difference in risk of recurrent stroke (HR 0.84, 95% CI 0.61–1.15) or MI (HR 0.83, 95% CI 0.52–1.34). Conclusion Long-term risks of all-cause mortality, recurrent stroke and MI are similar, or only slightly lower, in patients with lacunar/SVD as compared to other ischaemic stroke. Patients and physicians should be as vigilant in optimising short- and long-term secondary prevention of vascular events in lacunar/SVD as for other stroke types.

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Elevated Neutrophil to Lymphocyte Ratio Associated With Increased Risk of Recurrent Vascular Events in Older Minor Stroke or TIA Patients

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.646961 ◽

2021 ◽

Vol 13 ◽

Author(s):

Ka Lung Chan ◽

Xueyan Feng ◽

Bonaventure Ip ◽

Shangmeng Huang ◽

Sze Ho Ma ◽

...

Keyword(s):

Cardiovascular Events ◽

Older Patients ◽

Recurrent Stroke ◽

Neutrophil To Lymphocyte Ratio ◽

Minor Stroke ◽

Composite Outcome ◽

Vascular Events ◽

Lymphocyte Ratio ◽

Coronary Syndrome ◽

Increased Risk

BackgroundThe risk of recurrent stroke following a minor stroke or transient ischemic attack (TIA) is high, when inflammation might play an important role. We aimed to evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting composite cardiovascular events in patients with minor stroke and TIA.MethodsConsecutive patients with acute minor stroke or TIA admitted within 24 h of symptoms onset during a 5-year period in a prospective stroke registry were analyzed. We calculated the NLR dividing absolute neutrophil count by absolute lymphocyte count tested within 24 h of admission. NLR ≥4th quartile was defined as high NLR. A composite outcome was defined as stroke, acute coronary syndrome or vascular death within 1 year. We investigated associations between NLR and the composite outcome in univariate and multivariate analyses, among all patients and in those aged over 60 years (i.e., older patients).ResultsOverall, 841 patients (median age 68 years; 60.4% males) were recruited. No significant independent association was found between NLR and the composite outcome in multivariate analysis in the overall cohort. Among the 612 older patients (median age 73 years; 59.2% males), the median NLR was 2.76 (interquartile range 1.96−4.00) and 148 (24.2%) patients had high NLR. The composite outcome occurred in 77 (12.6%) older patients, who were more likely to have a high NLR (39.0% versus 22.1%; p = 0.001) than those without a composite outcome. In multivariate logistic regression, high NLR (adjusted odds ratio 2.00; 95% confidence interval 1.07−3.75; p = 0.031) was independently associated with the composite outcome in older patients.ConclusionIn older (aged ≥60 years) patients with acute minor stroke or TIA, a higher NLR, a marker of systemic inflammation that can be easily obtained in routine blood tests, is an independent predictor of subsequent cardiovascular events.

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Oxidized low-density lipoprotein predicts recurrent stroke in patients with minor stroke or TIA

Neurology ◽

10.1212/wnl.0000000000006118 ◽

2018 ◽

Vol 91 (10) ◽

pp. e947-e955 ◽

Cited By ~ 4

Author(s):

Anxin Wang ◽

Jie Xu ◽

Guojuan Chen ◽

David Wang ◽

S. Claiborne Johnston ◽

...

Keyword(s):

Proportional Hazards ◽

Recurrent Stroke ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cox Proportional Hazards ◽

Minor Stroke ◽

Low Density ◽

Oxidized Low Density Lipoprotein ◽

Vascular Events ◽

Secondary Outcomes

ObjectiveTo investigate the association between oxidized low-density lipoprotein (oxLDL) and recurrent stroke in patients with minor stroke or TIA.MethodsIn the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, baseline oxLDL levels were blindly measured in plasma with the 4E6 antibody in the core laboratory. The primary outcome was any stroke within 90 days. The secondary outcomes included any stroke within 1 year and ischemic stroke and combined vascular events within 90 days and 1 year. The associations of oxLDL with recurrent stroke were analyzed by Cox proportional hazards.ResultsAmong 3,019 patients included in this study, the median (interquartile range) of oxLDL was 13.96 (6.65–28.81) μg/dL. After adjustment for conventional confounding factors, patients in the highest oxLDL quartile (≥28.81 μg/dL) had a higher risk of recurrent stroke within 90 days (hazard ratio 1.43, 95% confidence interval 1.03–1.98) compared to those in the lowest oxLDL quartile (<6.65 μg/dL). Similar results were found for secondary outcomes. We also found a J-shaped association between oxLDL and risk of each outcome. There were no significant interactions between oxLDL and low-density lipoprotein and use of dual antiplatelet, antihypertensive, antidiabetic, and statins agents.ConclusionsElevated oxLDL levels can independently predict recurrent stroke in patients with minor stroke or TIA.ClinicalTrials.gov identifier:NCT00979589.

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High-sensitive C-reactive protein and dual antiplatelet in intracranial arterial stenosis

Neurology ◽

10.1212/wnl.0000000000004928 ◽

2018 ◽

Vol 90 (6) ◽

pp. e447-e454 ◽

Cited By ~ 5

Author(s):

Jiejie Li ◽

Anxin Wang ◽

Xingquan Zhao ◽

Liping Liu ◽

Xia Meng ◽

...

Keyword(s):

High Risk ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Recurrent Stroke ◽

Arterial Stenosis ◽

Minor Stroke ◽

Intracranial Arterial Stenosis ◽

C Reactive Protein ◽

Vascular Events ◽

Reactive Protein

ObjectiveTo determine the relationship of high-sensitive C-reactive protein (hsCRP) and the efficacy and safety of dual antiplatelet therapy in patients with and without intracranial arterial stenosis (ICAS) in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial.MethodsA subgroup of 807 patients with both magnetic resonance angiography images and hsCRP measurement was analyzed. Cox proportional hazards models were used to assess the interaction of hsCRP levels with the effects of dual and single antiplatelet therapy.ResultsA total of 358 (44.4%) patients had ICAS and 449 (55.6%) did not. The proportion of patients with elevated hsCRP levels was higher in the ICAS group than in the non-ICAS group (40.2% vs 30.1%, p = 0.003). There was significant interaction between hsCRP and the 2 antiplatelet therapy groups in their effects on recurrent stroke after adjustment for confounding factors in the patients with ICAS (p = 0.012), but not in those without (p = 0.256). Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the risk of recurrent stroke only in the patients with ICAS and nonelevated hsCRP levels (adjusted hazard ratio 0.27; 95% confidence interval 0.11 to 0.69; p = 0.006). Similar results were observed for composite vascular events. No significant difference in bleeding was found.ConclusionsPresence of both ICAS and nonelevated hsCRP levels may predict better response to dual antiplatelet therapy in reducing new stroke and composite vascular events in minor stroke or high-risk TIA patients. Further large-scale randomized and controlled clinical trials are needed to confirm this finding.

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