Oral Anticoagulation Timing in Patients with Acute Ischaemic Stroke and Atrial Fibrillation

Background and Purpose: Oral anticoagulants (OACs) prevent stroke recurrence and vascular embolism in patients with acute ischaemic stroke (AIS) and atrial fibrillation (AF). Current guidance recommends a “1-3-6-12 day”’ rule to resume OACs after AIS, based mainly on empirical consensus. This study investigated the suitability of guideline-recommended timing for OAC initiation. Methods: To overcome immortal time bias, we emulated a sequence of randomized placebo-controlled trials and constructed 90 propensity score-matched cohorts of 12,307 patients with AF and AIS from 2012 to 2016. We compared the risk of composite effectiveness and safety outcome in the early vs no OAC use group and in the delayed vs no OAC use. Indirect comparison between early and delayed use was conducted using a network meta-analysis. Results: Across the groups of AIS severity, the risks of composite outcome or effectiveness outcome were lower in the OAC use group than the no use group and the risks were similar between the early and delayed use groups. In patients with severe AIS, those receiving early OACs use had an increased risk of safety outcome, with HR of 2.10 (CI: 1.13-3.92) compared with those without OAC use, and HR of 1·44 (CI: 0·99-2·09) compared with those receiving delayed use. Conclusions: In AF patients with severe AIS, early OAC use before the guideline-recommended days appeared to increase the risk of bleeding events, although the OAC initiation time seemed not to affect the risk of serious vascular events. The optimal severity-specific timing for OAC initiation after AIS requires further evaluation

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Abstract 16732: Urinary 11-Dehydro-Thromboxane B2 is Associated With Vascular and Non-Vascular Events in Atrial Fibrillation Patients

Circulation ◽

10.1161/circ.130.suppl_2.16732 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Daniele Pastori ◽

Pasquale Pignatelli ◽

Roberto Cangemi ◽

William Hiatt ◽

Alessio Farcomeni ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiovascular Events ◽

Oral Anticoagulants ◽

Cardiovascular Death ◽

Cox Proportional Hazards ◽

Thromboxane B2 ◽

Vascular Events ◽

Residual Cardiovascular Risk ◽

Increased Risk ◽

Anticoagulated Patients

Introduction: Non-Valvular Atrial Fibrillation (AF) patients show high residual cardiovascular risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of cardiovascular events, but its predictive value in anticoagulated AF patients is unknown. Hypothesis: Aim of this was to assess whether urinary 11-dehydro-TxB2 is a predictor of cardiovascular events in anticoagulated patients with AF. Methods: Prospective single-center cohort study, including 864 consecutive AF patients. Mean time of follow-up was 30.0 months yielding 2062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end-point was the composite of myocardial infarction, ischemic stroke, cardiac revascularization, cardiovascular death and deaths from any cause. Results: Cardiovascular events occurred in 98 (11.3%), whilst 81 patients died (9.4%), including 55 from cardiovascular and 26 from non-cardiovascular causes. At baseline, urinary 11-dehydro-TxB2 levels were higher in patients who experienced a cardiovascular event (p<0.001). An increased rate of cardiovascular events, cardiovascular death and all-cause death was observed across tertiles of 11-dehydro-TxB2 (p<0.001). On Cox proportional hazards analysis, CHA2DS2-VASc score, second and third tertile of 11-dehydro-TxB2, compared to the first tertile, were significant predictors of vascular and non-vascular events. On a logistic regression analysis, 11-dehydro-TxB2 levels progressively increase with increasing CHA2DS2-VASc scores. Conclusions: Urinary 11-dehydro-TxB2 predicts residual risk of cardiovascular events in anticoagulated atrial fibrillation patients. Urinary 11-dehydro-TxB2 progressively increases with increasing CHA2DS2-VASc score suggesting that anticoagulated patients with high CHA2DS2-VASc score may need additional antithrombotic strategies.

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Should the Presence or Extent of Coronary Artery Disease be Quantified in the CHA2DS2-VASc Score in Atrial Fibrillation? A Report from the Western Denmark Heart Registry

Thrombosis and Haemostasis ◽

10.1055/s-0038-1675401 ◽

2018 ◽

Vol 118 (12) ◽

pp. 2162-2170 ◽

Cited By ~ 11

Author(s):

Kamilla Steensig ◽

Kevin Olesen ◽

Troels Thim ◽

Jens Nielsen ◽

Svend Jensen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Coronary Artery Disease ◽

Risk Factor ◽

Coronary Artery ◽

Coronary Angiography ◽

Ischaemic Stroke ◽

Independent Risk Factor ◽

Oral Anticoagulants ◽

Increased Risk ◽

Artery Disease

Background Patients with atrial fibrillation (AF) have an increased risk of ischaemic stroke. The risk can be predicted by the CHA2DS2-VASc score, in which the vascular component refers to previous myocardial infarction, peripheral artery disease and aortic plaque, whereas coronary artery disease (CAD) is not included. Objectives This article explores whether CAD per se or extent provides independent prognostic information of future stroke among patients with AF. Materials and Methods Consecutive patients with AF and coronary angiography performed between 2004 and 2012 were included. The endpoint was a composite of ischaemic stroke, transient ischaemic attack and systemic embolism. The risk of ischaemic events was estimated according to the presence and extent of CAD. Incidence rate ratios (IRR) were calculated in reference to patients without CAD and adjusted for parameters included in the CHA2DS2-VASc score and treatment with anti-platelet agents and/or oral anticoagulants. Results Of 96,430 patients undergoing coronary angiography, 12,690 had AF. Among patients with AF, 7,533 (59.4%) had CAD. Mean follow-up was 3 years. While presence of CAD was an independent risk factor for the composite endpoint (adjusted IRR, 1.25; 1.06–1.47), extent of CAD defined as 1-, 2-, 3- or diffuse vessel disease did not add additional independent risk information. Conclusion Presence, but not extent, of CAD was an independent risk factor of the composite thromboembolic endpoint beyond the components already included in the CHA2DS2-VASc score. Consequently, we suggest that significant angiographically proven CAD should be included in the vascular disease criterion in the CHA2DS2-VASc score.

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Gastrointestinal bleeding during acute ischaemic stroke hospitalisation increases the risk of stroke recurrence

Stroke and Vascular Neurology ◽

10.1136/svn-2019-000314 ◽

2020 ◽

Vol 5 (2) ◽

pp. 116-120

Author(s):

Wanliang Du ◽

Xingquan Zhao ◽

Yilong Wang ◽

Yuesong Pan ◽

Gaifen Liu ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Patient Characteristics ◽

Recurrence Risk ◽

Stroke Recurrence ◽

Gi Bleeding ◽

Stroke Registry ◽

Risk Of Death ◽

Increased Risk ◽

Death And Loss

ObjectiveGastrointestinal (GI) bleeding in patients who had a stroke is strongly associated with a higher risk of death and loss of independence. However, it is unknown whether GI bleeding increases risk for recurrence of stroke. In this study, we assess the potential relationship between GI bleeding and stroke recurrence in patients within 12 months of an acute ischaemic stroke (AIS), using the China National Stroke Registry (CNSR).MethodsThis study included 22 216 patients who had an ischaemic stroke included in the CNSR from 2007 to 2008. We analysed baseline patient characteristics, GI bleeding and outcomes of patients who had an AIS, specifically stroke recurrence at 3, 6 and 12 months. We used multivariable logistic regression to evaluate a possible association between GI bleeding and stroke recurrence.ResultsOf the 12 415 patients included in our study, 12.3%, 15.5% and 17.7% had a stroke recurrence at 3, 6 and 12 months, respectively. GI bleeding was an independent stroke recurrence risk factor in patients after ischaemic stroke at 3 months (adjusted OR 1.481, 95% CI 1.118 to 1.962), 6 months (adjusted OR 1.448, 95% CI 1.106 to 1.896) and 12 months (adjusted OR 1.350; 95% CI 1.034 to 1.763).ConclusionGI bleeding was associated with the increased risk of stroke recurrence after an AIS.

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The NOACs in special situations: the elderly, renal impairment, combination with antiplatelet agents and thrombolytics

ESC CardioMed ◽

10.1093/med/9780198784906.003.0057 ◽

2018 ◽

pp. 273-278

Author(s):

Felicita Andreotti ◽

Eliano Pio Navarese ◽

Filippo Crea

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Oral Anticoagulants ◽

Factor Xa ◽

Antiplatelet Agents ◽

Clinical History ◽

The Elderly ◽

Arterial Disease ◽

Baseline Risk

Phase III randomised trials indicate that the non-vitamin K antagonist oral anticoagulants (NOACs) are preferable to warfarin in elderly, non-valvular atrial fibrillation patients, given a lower incidence of intracranial haemorrhage, a favourable overall efficacy and safety profile, and the lack of routine monitoring, although care is needed to dose-adjust for kidney function and to prevent gastrointestinal bleeds, depending on the NOAC. Advanced age should not exclude the use of any NOAC. Overall, NOACs perform well, relative to warfarin or aspirin, irrespective of renal function. However, all NOACs undergo variable renal clearance, and in Europe a creatinine clearance of less than 30 mL/min contraindicates dabigatran and less than 15 mL/min the factor Xa inhibitors. Trial outcomes stratified by antiplatelet therapy, after adjustment for baseline risk, show that concomitant antiplatelet use does not significantly alter the overall treatment effects of NOACs versus warfarin. Whether adding an antiplatelet to a NOAC in atrial fibrillation patients with arterial disease is beneficial requires randomized controlled testing. Current guidelines recommend that patients effectively anticoagulated with a NOAC who develop an acute ischaemic stroke should not be considered for thrombolysis unless clinical history or laboratory tests indicate low or no anticoagulation or at least two half-lives have elapsed from the last NOAC dose. Retrospective data suggest no prohibitive adverse events among selected NOAC-treated patients with acute ischaemic stroke receiving thrombolysis. Further investigation in this setting is warranted.

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Rationale and design of the Registry of Acute Stroke Under Novel Oral Anticoagulants-prime (RASUNOA-prime)

European Stroke Journal ◽

10.1177/2396987318812644 ◽

2018 ◽

Vol 4 (2) ◽

pp. 181-188 ◽

Cited By ~ 2

Author(s):

Kirsten Haas ◽

Jan C Purrucker ◽

Timolaos Rizos ◽

Peter U Heuschmann ◽

Roland Veltkamp

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Vitamin K ◽

Intracerebral Haemorrhage ◽

Acute Ischaemic Stroke ◽

Emergency Treatment ◽

Clinical Course ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Stroke Patients

Background Anticoagulation with vitamin K antagonists and non-vitamin K antagonists oral anticoagulants (NOAC) is effective in stroke prevention in patients with atrial fibrillation. However, anticoagulation also poses a major challenge for emergency treatment of patients suffering ischaemic stroke or intracerebral haemorrhage. Aim The registry RASUNOA-prime is designed to describe current patterns of emergency management, clinical course and outcome of patients with atrial fibrillation experiencing an acute ischaemic stroke or intracerebral haemorrhage under different anticoagulation schemes prior to stroke (NOAC, vitamin K antagonists or no anticoagulation). Methods and design RASUNOA-prime (ClinicalTrials.gov, NCT02533960) is a prospective, investigator-initiated, multicentre, observational cohort study aiming to recruit 3000 patients with acute ischaemic stroke and atrial fibrillation, and 1000 patients with acute intracerebral haemorrhage and atrial fibrillation with different anticoagulation schemes pre-stroke. It is a non-interventional triple-armed study aiming at a balanced inclusion of ischaemic stroke and intracerebral haemorrhage patients according to the different anticoagulation schemes. Patients will be followed up for clinical course, management and outcome up to three months after the event. Findings in ischaemic stroke and intracerebral haemorrhage patients on NOAC will be compared with patients taking vitamin K antagonists or no anticoagulant pre-stroke. Study outcomes Primary endpoint for ischaemic stroke patients: occurrence of symptomatic intracerebral haemorrhage, for intracerebral haemorrhage patients: occurrence of secondary haematoma expansion. Secondary endpoints include assessment of coagulation, use of thrombolysis and/or mechanical thrombectomy, occurrence of complications, implementation of secondary prevention. Summary Describing the current patterns of early management as well as outcome of stroke patients with atrial fibrillation will help guide physicians to develop recommendations for emergency treatment of stroke patients under different anticoagulation schemes.

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Transient atrial fibrillation and risk of stroke after acute myocardial infarction

Thrombosis and Haemostasis ◽

10.1160/th11-05-0343 ◽

2011 ◽

Vol 106 (11) ◽

pp. 877-884 ◽

Cited By ~ 16

Author(s):

Rema Bishara ◽

Gregory Telman ◽

Fadel Bahouth ◽

Jonathan Lessick ◽

Doron Aronson

Keyword(s):

Myocardial Infarction ◽

Atrial Fibrillation ◽

Acute Myocardial Infarction ◽

Ischaemic Stroke ◽

Hospital Discharge ◽

Oral Anticoagulants ◽

Antiplatelet Agents ◽

Increased Risk ◽

One Year ◽

The Impact

SummaryAtrial fibrillation (AF) is a frequent complication of acute myocardial infarction (AMI). In the AMI setting, AF is frequently brief and attributed to acute haemodynamic changes, inflammation or ischaemia. However, it remains uncertain whether transient AF episodes are associated with a subsequent increased risk of ischaemic stroke. We studied the impact of transient new-onset AF on the one-year risk of ischaemic stroke or transient ischaemic attack (TIA) in a retrospective cohort of 2,402 patients with AMI. Patients with previous AF or AF at hospital discharge were excluded. Transient AF occurred in 174 patients (7.2%) during the initial hospitalisation. During one year follow-up after hospital discharge, stroke or TIA occurred in 16 (9.2%) and 58 (2.6%) patients with and without transient AF, respectively (p< 0.0001). Compared with patients without transient AF, the adjusted hazard ratio for stroke or TIA in patients with transient AF was 3.03 (95% CI 1.73–5.32; p< 0.0001). Stroke or TIA occurred in 2.6% of patients without AF, 6.3% of patients with transient AF treated with oral anticoagulants, and 9.9% of patients with transient AF treated with antiplatelet agents. The incidence of recurrent AF after hospital discharge was markedly higher in patients with transient AF during the index hospitalisation (22.8% vs. 2.0%, p< 0.0001). In conclusion, transient AF complicating AMI is associated with an increased future risk of ischaemic stroke and TIA, particularly in patients treated with antiplatelet agents alone. High AF recurrence rates in these patients also suggest that oral anticoagulants should be strongly considered.

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Early versus late start of direct oral anticoagulants after acute ischaemic stroke linked to atrial fibrillation: an observational study and individual patient data pooled analysis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-327236 ◽

2021 ◽

pp. jnnp-2021-327236

Author(s):

Gian Marco De Marchis ◽

David J. Seiffge ◽

Sabine Schaedelin ◽

Duncan Wilson ◽

Valeria Caso ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Individual Patient Data ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Pooled Analysis ◽

Patient Data ◽

Optimal Timing ◽

Significant Difference

ObjectiveThe optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) versus late (>5 days of AIS) DOAC-start.MethodsThis is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH.ResultsA total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke.ConclusionsOur results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.

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Effects of Early Hypertension Control after Ischaemic Stroke on the Outcome: A Meta-Analysis

Cerebrovascular Diseases ◽

10.1159/000441097 ◽

2015 ◽

Vol 40 (5-6) ◽

pp. 270-278 ◽

Cited By ~ 10

Author(s):

Shuping Liu ◽

Chengyan Li ◽

Tao Li ◽

Jing Xiong ◽

Xueqing Zhao

Keyword(s):

Ischaemic Stroke ◽

Meta Analysis ◽

Cochrane Collaboration ◽

Good Choice ◽

Stroke Recurrence ◽

Hypertension Control ◽

Vascular Events ◽

Haemorrhagic Transformation ◽

Review Manager

Background: Accumulating evidence suggests that high blood pressure (BP) increases the risk of cerebral oedema and haemorrhagic transformation of the ischaemic stroke (IS), and that low BP in acute ischaemic stroke (AIS) is associated with a poor prognosis. The best possible management of hypertension after AIS is still uncertain. Materials and Methods: English databases were searched to identify relevant randomized controlled trials assessing the effects of early BP lowering (started within the first 48 h) after IS on outcome from January 1990 to August 2015. We set strict inclusion criteria and used the Review Manager 5.2 software from Cochrane Collaboration to calculate the combined risk ratio (RR). Result: Eight studies met our criteria. Early BP lowering after AIS did not significantly affect the risk of early and long-term death (RR 1.22; 95% CI 0.69-2.16 and RR 1.03; 95% CI 0.62-1.71), early and long-term dependency (RR 1.02; 95% CI 0.94-1.10 and RR 1.07; 95% CI 0.84-1.36), early and long-term death or dependency (RR 1.04; 95% CI 0.94-1.19 and RR 1.00; 95% CI 0.95-1.05), long-term stroke recurrence (RR 0.74; 95% CI 0.49-1.11), long-term myocardial infarction (RR 0.99; 95% CI 0.27-3.61), and long-term vascular events (RR 0.97; 95% CI 0.72-1.31). Conclusion: Our results revealed neither support nor opposition to early BP lowering (started within 48 h) after AIS; individualized BP management based on the patients' condition may be a good choice.

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Prognostic significance of international normalised ratio and prothrombin time in Chinese acute ischaemic stroke patients

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2021-141204 ◽

2022 ◽

pp. postgradmedj-2021-141204

Author(s):

Shoujiang You ◽

Qiao Han ◽

Xiaofeng Dong ◽

Chongke Zhong ◽

Huaping Du ◽

...

Keyword(s):

Logistic Regression ◽

Ischaemic Stroke ◽

Prothrombin Time ◽

Hospital Discharge ◽

Acute Ischaemic Stroke ◽

Regression Models ◽

Logistic Regression Models ◽

Risk Of Death ◽

Increased Risk ◽

International Normalised Ratio

BackgroundWe investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients.MethodsA total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92–0.98), Q3 (0.98–1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4–5) separately on discharge in AIS patients.ResultsHaving an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend=0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend=0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend=0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend=0.006) but not death or major disability (P-trend=0.240), major disability (P-trend=0.606) on discharge.ConclusionsHigh INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.

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Successful thrombolysis in essential thrombocythemia-related acute ischaemic stroke

BMJ Case Reports ◽

10.1136/bcr-2021-242925 ◽

2021 ◽

Vol 14 (5) ◽

pp. e242925

Author(s):

Ishita Desai ◽

Ashutosh Tiwari ◽

Mritunjai Kumar Singh ◽

Niraj Kumar

Keyword(s):

Ischaemic Stroke ◽

Essential Thrombocythemia ◽

Acute Ischaemic Stroke ◽

Jak2 V617f ◽

Preliminary Evidence ◽

Sudden Onset ◽

Left Ventricular ◽

Interesting Case ◽

Increased Risk ◽

Successful Thrombolysis

Essential thrombocythemia (ET)-related acute ischaemic stroke (AIS) may account for approximately 0.25%–0.5% of all ischaemic strokes. If left undiagnosed and untreated, patients with ET carry an increased risk of recurrent thrombosis involving major organs including the brain. We report an interesting case of a 67-year-old man, who was successfully thrombolysed for AIS resulting from ET. He presented with sudden onset of left-sided hemiparesis with a left-ventricular clot. His subsequent investigations including positive JAK2 V617F mutation confirmed the diagnosis of ET. He made a significant recovery with thrombolysis, anticoagulation, antiplatelet and hydroxyurea. A fear of post-thrombolytic haemorrhagic complications appears the major reason for the lack of reports of thrombolysis in ET-related AIS. Although the diagnosis of ET was confirmed on subsequent investigations, successful thrombolysis in our case provides preliminary evidence that ET-related AIS cases can undergo successful thrombolysis using tenecteplase. To date, ours is only the second case of ET-related AIS being thrombolysed.

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