Baseline D-Dimer Levels as a Risk Assessment Biomarker for Recurrent Stroke in Patients with Combined Atrial Fibrillation and Atherosclerosis

Background: We investigated the effect of D-dimer levels and efficacy of different antithrombotic therapies according to the baseline D-dimer levels on recurrent stroke in patients with atrial fibrillation (AF)-related stroke and atherosclerosis. Methods: We enrolled 1441 patients with AF-related stroke and atherosclerosis in this nationwide multicenter study. The primary outcome measure was the occurrence of recurrent ischemic stroke over a 3-year period. Results: High D-dimer levels (≥2 μg/mL) were significantly associated with higher risk of recurrent ischemic stroke (adjusted hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.13–2.84; p = 0.012). The risk of recurrent stroke was similar between the anticoagulant and the antiplatelet groups in all subjects (adjusted HR, 0.78; 95% CI, 0.46–1.32; p = 0.369). However, in patients with high D-dimer levels (≥2 μg/mL), risk of recurrent stroke was significantly lower in the anticoagulant group than in the antiplatelet group (adjusted HR, 0.40; 95% CI, 0.18–0.87; p = 0.022). Conclusion: Our findings suggested that baseline D-dimer levels could be used as a risk assessment biomarker of recurrent stroke in patients with AF-related stroke and atherosclerosis. High D-dimer levels would facilitate the identification of patients who are more likely to benefit from anticoagulants to ensure secondary prevention of stroke.

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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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Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy?

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2018-013784 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1132-1136 ◽

Cited By ~ 5

Author(s):

Dylan N Wolman ◽

Michael Iv ◽

Max Wintermark ◽

Gregory Zaharchuk ◽

Michael P Marks ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure ◽

Large Vessel Occlusion ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Endovascular Thrombectomy ◽

Perfusion Weighted Imaging

Background and purposeAcute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).Materials and methodsThis retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.ResultsTwo hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529).ConclusionAIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

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Increasing trends in hospitalisations due to atrial fibrillation in Australia from 1993 to 2013

Heart ◽

10.1136/heartjnl-2018-314471 ◽

2019 ◽

Vol 105 (17) ◽

pp. 1358-1363 ◽

Cited By ~ 18

Author(s):

Celine Gallagher ◽

Jeroen ML Hendriks ◽

Lynne Giles ◽

Jonathan Karnon ◽

Clarabelle Pham ◽

...

Keyword(s):

Atrial Fibrillation ◽

Primary Outcome ◽

Outcome Measure ◽

Incidence Rate Ratio ◽

Healthcare Delivery ◽

Primary Outcome Measure ◽

Annual Change ◽

Population Changes ◽

Rate Of Increase ◽

Increasing Trends

ObjectiveThe aim of this study is to characterise hospitalisations due to atrial fibrillation (AF) compared with two other common cardiovascular conditions, myocardial infarction (MI) and heart failure (HF), in addition to the associated economic burden of these hospitalisations and contribution of AF-related procedures.MethodsThe primary outcome measure was the rate of increase of AF, MI and HF hospitalisations from 1993 to 2013. The rate of increase of AF-related procedures including cardioversion and ablation were also collected, in addition to direct costs associated with hospitalisations for each of these three conditions.ResultsAF hospitalisations increased 295% over the 21-year period to a total of 61 424 in 2013. In comparison, MI and HF hospitalisations increased by only 73% and 39%, respectively, over the same period. Considering population changes, there was an annual increase in AF hospitalisations of 5.2% (incidence rate ratio [IRR] 1.052; 95% CI 1.046 to 1.059; p<0.001). In contrast, there was a 2.2% increase per annum for MI (IRR 1.022; 95% CI 1.017 to 1.027; p<0.001) and negligible annual change for HF hospitalisations (IRR 1.000; 95% CI 0.997 to 1.002; p=0.78). Cardioversion and AF ablation increased by 10% and 26% annually, respectively. AF hospitalisation costs rose by 479% over the 21-year period, an increase that was more than double that of MI and HF.ConclusionsThe burden of AF hospitalisations continues to rise unabated. AF has now surpassed both MI and HF hospitalisations and represents a growing cost burden. New models of healthcare delivery are required to stem this growing healthcare burden.

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Clinical outcome with NOACs vs VKAs in patients with atrial fibrillation and severe chronic kidney disease: results of a retrospective, multicenter, real-world study

European Heart Journal ◽

10.1093/ehjci/ehaa946.3365 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

V Lio ◽

V Pasceri ◽

L Di Lullo ◽

V Russo ◽

F Fimiani ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Real World ◽

Primary Outcome ◽

Outcome Measure ◽

Composite Endpoint ◽

Primary Outcome Measure ◽

Vitamin K Antagonist ◽

Minor Bleeding ◽

Severe Chronic Kidney Disease

Abstract Background Patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD) are at higher risk of both bleeding and thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) are licensed to be used in these patients, although they were excluded from phase III controlled randomized trials comparing NOACs vs warfarin in AF. Thus, current evidence on NOACs use in such setting of patients is not definitive. Purpose Aim of our multicenter study was to perform a real-world comparison of clinical outcome with NOACs vs vitamin K antagonist anticoagulants (VKAs) also in AF patients having an estimated glomerular filtration rate (eGFR) 15–29 mL/min. Methods We retrospectively included a total of 266 patients receiving NOACs (N=159) or VKAs (N=107). Primary outcome measure was the cumulative incidence of the net composite endpoint including ischemic stroke, systemic thromboembolism or any bleeding. Mean follow-up was 2.6 years. Results CHA2DS2-VASc and HAS-BLED scores at baseline were similar in the two groups (3.4±1.3 with NOACs vs 3.4±0.9 with VKAs and 3.1±1.0 vs 3.0±0.7, respectively); eGFR and hemoglobin values were also comparable (31.8±12.3 vs 32±11.9 mL/min and 10.2±2.1 vs 11.0±2.3 g/dL, respectively). NOACs were not inferior to VKAs for the primary net composite endpoint: incidence 20.7% vs 29.9%, p<0.01 for non-inferiority, p=0.11 for superiority. In proportional Cox regression model, hazard ratio for the primary outcome measure with NOACs use was 0.74 (95% CI 0.45–1.21, p=0.22). In the NOAC group there was a trend towards reduction in minor bleeding complications (p=0.08). Conclusions Our real-world data indicate that in patients with AF and severe renal failure NOACs are not inferior to VKAs for both safety and efficacy. The use of NOACs was associated with a numerically lower incidence of minor bleeding. Funding Acknowledgement Type of funding source: None

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CHA2DS2-VASc score in acute ischemic stroke with atrial fibrillation: results from the Clinical Research Collaboration for Stroke in Korea

Scientific Reports ◽

10.1038/s41598-020-80874-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hak-Loh Lee ◽

Joon-Tae Kim ◽

Ji Sung Lee ◽

Beom Joon Kim ◽

Jong-Moo Park ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Primary Outcome ◽

Research Collaboration ◽

Recurrent Stroke ◽

Oral Anticoagulants ◽

Vascular Events ◽

Stroke Registry ◽

One Year

AbstractWe investigated a multicenter registry to identify estimated event rates according to CHA2DS2-VASc scores in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). The additional effectiveness of antiplatelets (APs) plus oral anticoagulants (OACs) compared with OACs alone considering the CHA2DS2-VASc scores was also explored. This study retrospectively analyzed a multicenter stroke registry between Jan 2011 and Nov 2017, identifying patients with acute ischemic stroke with AF. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 1 year. A total of 7395 patients (age, 73 ± 10 years; men, 54.2%) were analyzed. The primary outcome events at one year ranged from 5.99% (95% CI 3.21–8.77) for a CHA2DS2-VASc score of 0 points to 30.45% (95% CI 24.93–35.97) for 7 or more points. After adjustments for covariates, 1-point increases in the CHA2DS2-VASc score consistently increased the risk of primary outcome events (aHR 1.10 [1.06–1.15]) at 1-year. Among OAC-treated patients at discharge (n = 5500), those treated with OAC + AP (vs. OAC alone) were more likely to experience vascular events, though among patients with a CHA2DS2-VASc score of 5 or higher, the risk of primary outcome in the OAC + AP group was comparable to that in the OAC alone group (Pint = 0.01). Our study found that there were significant associations of increasing CHA2DS2-VASc scores with the increasing risk of vascular events at 1-year in AIS with AF. Further study would be warranted.

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The Addition of MRI to CT Based Stroke and TIA Evaluation Does Not Impact One year Outcomes

The Open Neurology Journal ◽

10.2174/1874205x01307010017 ◽

2013 ◽

Vol 7 (1) ◽

pp. 17-22 ◽

Cited By ~ 3

Author(s):

Hebah Hefzy ◽

Elizabeth Neil ◽

Patricia Penstone ◽

Meredith Mahan ◽

Panayiotis Mitsias ◽

...

Keyword(s):

Outcome Measures ◽

Primary Outcome ◽

Outcome Measure ◽

Recurrent Stroke ◽

Multiple Logistic Regression Analysis ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Ct Angiogram ◽

Primary Stroke Center ◽

One Year

Background: The 2010 American Academy of Neurology guideline for the diagnosis of acute ischemic stroke recommends MRI with diffusion weighted imaging (DWI) over noncontrast head CT. No studies have evaluated the influence of imaging choice on patient outcome. We sought to evaluate the variables that influenced one-year outcomes of stroke and TIA patients, including the type of imaging utilized. Methods: Patients were identified from a prospectively collected stroke and TIA database at a single primary stroke center during a one-year period. Data were abstracted from patient electronic medical records. The primary outcome measure was death, myocardial infarction, or recurrent stroke within the following year. Secondary outcome measures included predictors of getting an MRI study. Results: 727 consecutive patients with a discharge diagnosis of stroke or TIA were identified (616 and 111 respectively); 536 had CT and MRI, 161 had CT alone, 29 had MRI alone, and one had no neuroimaging. On multiple logistic regression analysis, there were no differences in primary or secondary outcome measures among different imaging strategies. Predictors of the primary outcome measure included age and NIHSS, while performance of a CT angiogram (CTA) predicted a decreased odds of death, stroke, or MI. The strongest predictor of having an MRI was admission to a stroke unit. Conclusions: These results suggest that long-term (one-year) patient outcomes may not be influenced by imaging strategy. Performance of a CTA was protective in this cohort. A randomized trial of different imaging modalities should be considered.

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Abstract TMP6: NIH Stroke Scale as the Primary Outcome Measure for Trials of Acute Treatment of Ischemic Stroke

Stroke ◽

10.1161/str.50.suppl_1.tmp6 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Vicky Chalos ◽

Nadinda van der Ende ◽

Hester F Lingsma ◽

Maxim J Mulder ◽

Esmee Venema ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Treatment ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure

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National Institutes of Health Stroke Scale

Stroke ◽

10.1161/strokeaha.119.026791 ◽

2020 ◽

Vol 51 (1) ◽

pp. 282-290 ◽

Cited By ~ 3

Author(s):

Vicky Chalos ◽

Nadinda A.M. van der Ende ◽

Hester F. Lingsma ◽

Maxim J.H.L. Mulder ◽

Esmee Venema ◽

...

Keyword(s):

Ischemic Stroke ◽

Endovascular Treatment ◽

Treatment Effect ◽

Acute Treatment ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure ◽

National Institutes Of Health ◽

Unique Identifier ◽

Mr Clean

Background and Purpose— The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods— We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results— In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22–2.32) to respectively 1.36 (95% CI, 0.97–1.91) and 1.24 (95% CI, 0.87–1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions— The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties. Clinical Trial Registration— URL: http://www.isrctn.com . Unique identifier: ISRCTN10888758; https://www.clinicaltrials.gov . Unique identifier: NCT00359424.

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Stroke Prevention: Managing Modifiable Risk Factors

Stroke Research and Treatment ◽

10.1155/2012/391538 ◽

2012 ◽

Vol 2012 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Silvia Di Legge ◽

Giacomo Koch ◽

Marina Diomedi ◽

Paolo Stanzione ◽

Fabrizio Sallustio

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Secondary Prevention ◽

Stroke Prevention ◽

Recurrent Stroke ◽

Lifestyle Changes ◽

Thrombin Inhibitors ◽

Modifiable Risk Factors ◽

Vascular Events

Prevention plays a crucial role in counteracting morbidity and mortality related to ischemic stroke. It has been estimated that 50% of stroke are preventable through control of modifiable risk factors and lifestyle changes. Antihypertensive treatment is recommended for both prevention of recurrent stroke and other vascular events. The use of antiplatelets and statins has been shown to reduce the risk of recurrent stroke and other vascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are indicated in stroke prevention because they also promote vascular health. Effective secondary-prevention strategies for selected patients include carotid revascularization for high-grade carotid stenosis and vitamin K antagonist treatment for atrial fibrillation. The results of recent clinical trials investigating new anticoagulants (factor Xa inhibitors and direct thrombin inhibitors) clearly indicate alternative strategies in stroke prevention for patients with atrial fibrillation. This paper describes the current landscape and developments in stroke prevention with special reference to medical treatment in secondary prevention of ischemic stroke.

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Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation

European Heart Journal ◽

10.1093/ehjci/ehaa946.2431 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Giustozzi

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Primary Outcome ◽

Oral Anticoagulants ◽

Early Recurrence ◽

Optimal Timing ◽

Hemorrhagic Event

Abstract Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None

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