scholarly journals Antithrombotic Treatment of Embolic Stroke of Undetermined Source

Stroke ◽  
2020 ◽  
Vol 51 (6) ◽  
pp. 1758-1765 ◽  
Author(s):  
Hans-Christoph Diener ◽  
Ralph L. Sacco ◽  
J. Donald Easton ◽  
Christopher B. Granger ◽  
Michal Bar ◽  
...  
Keyword(s):  
Renal Function ◽  
Major Bleeding ◽  
Recurrent Stroke ◽  
Dabigatran Etexilate ◽  
Hazard Ratio ◽  
Embolic Stroke ◽  
Thrombin Inhibitor ◽  
Antithrombotic Treatment ◽  
Double Blind ◽  
The Impact

Background and Purpose— The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods— RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results— The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39–0.82]; interaction P =0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43–0.94]; interaction P =0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions— In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02239120.

scholarly journals Dabigatran or Aspirin in East Asian Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2021 ◽  
Vol 52 (3) ◽  
pp. 1069-1073
Author(s):  
Shinichiro Uchiyama ◽  
Kazunori Toyoda ◽  
Byung-Chul Lee ◽  
Chia-Wei Liou ◽  
Lawrence Ka Sing Wong ◽  
...  
Keyword(s):  
East Asia ◽  
Major Bleeding ◽  
Recurrent Stroke ◽  
East Asian ◽  
Hazard Ratio ◽  
Embolic Stroke ◽  
Thrombin Inhibitor ◽  
Asian Patients ◽  
Significant Difference ◽  
East Asian Patients

Background and Purpose: We assessed the outcomes of dabigatran versus aspirin in a prespecified subgroup analysis of East Asian patients with embolic stroke of undetermined source in the RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source). Methods: Patients with a recent embolic stroke of undetermined source were randomized to dabigatran (150 or 110 mg BID) or aspirin (100 mg QD). The primary efficacy outcome was recurrent stroke; the primary safety outcome was major bleeding. The East Asia cohort was compared with patients from all other countries (non-East Asia cohort). Results: Overall, 988 of 5390 patients (18%) were randomized in East Asia. During a median follow-up of 18.8 months, there was no statistically significant difference in recurrent stroke (hazard ratio, 0.65 [95% CI, 0.41–1.03]) or major bleeding (hazard ratio, 1.04 [95% CI, 0.57–1.91]) in East Asian patients receiving dabigatran versus aspirin. Death from any cause occurred more often in the dabigatran versus the aspirin group (hazard ratio, 3.98 [95% CI, 1.32–12.01]). Conclusions: The treatment effect of dabigatran versus aspirin was consistent between cohorts, with no apparent superiority for dabigatran over aspirin in preventing recurrent stroke in patients with embolic stroke of undetermined source. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.

Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale

Stroke ◽  
2021 ◽  
Author(s):  
Hans-Christoph Diener ◽  
Aurauma Chutinet ◽  
J. Donald Easton ◽  
Christopher B. Granger ◽  
Eva Kleine ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Antiplatelet Therapy ◽  
Patent Foramen Ovale ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Dabigatran Etexilate ◽  
Embolic Stroke ◽  
Thrombin Inhibitor ◽  
Foramen Ovale ◽  
Significant Difference

Background and Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43–1.14]) for ischemic stroke. Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.

scholarly journals Rivaroxaban dosing in patients with atrial fibrillation: results from the RIVER registry – is dosing according to renal function appropriate?

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A.J Camm ◽  
S Virdone ◽  
K.A.A Fox ◽  
K.S Pieper ◽  
J Beyer-Westendorf ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Renal Impairment ◽  
Major Bleeding ◽  
Cardiovascular Mortality ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Real Life ◽  
High Dose ◽  
The Impact

Abstract Introduction Rivaroxaban is recommended as an option for anticoagulation in patients with nonvalvular atrial fibrillation (AF) with one or more risk factors for stroke. The approved/recommended rivaroxaban dose for stroke prevention in patients with atrial fibrillation (AF) is solely based on renal function: 20 mg once daily (od) for patients with a creatinine clearance [CrCl] ≥50 ml/min and 15 mg od in patients with CrCl 15–49 mL/min). Purpose To assess the patterns of rivaroxaban prescription as per the creatinine clearances levels and to assess the impact of the rivaroxaban dosing on the rate of events at 2-year follow-up in patients with AF. Methods RIVaroxaban Evaluation in Real Life setting (RIVER) is a prospective international registry of patients with newly diagnosed non-valvular AF treated with rivaroxaban for the prevention of thromboembolic stroke and at least one investigator-determined risk factor for stroke. Adjusted hazard ratios (HRs) were obtained through Cox proportional-hazard model. Results Among 3402 patients with normal renal function (CrCl ≥50 mL/min), 82.1% were prescribed the recommended rivaroxaban dose of 20 mg (od) at baseline. Among 524 patients with moderate or severe renal impairment (CrCl 15–50 mL/min), 55.3% patients received rivaroxaban 15 mg (od), 39.9% received 20 mg (od) and 4.2% 10 mg (od). Non-recommended dosing was rare in patients younger than 70 (13.5%) but more frequent in older patients (28.8%). Non-recommended low dosing was more frequent in Asians (38.9%), compared to non-Asian patients (13.8%). Regarding clinical outcomes, adjusted hazards ratios (HR, presented with 95% confidence intervals) showed that the non-recommended low dosing (&lt;20 mg od) was associated with higher risk of non-cardiovascular mortality (HR 2.09 (1.16–3.77)) in patients with normal renal function. The non-recommended high dosing (&gt;15 mg od) was associated with lower risk of all-cause mortality (HR 0.63 (0.42–0.93)) and cardiovascular mortality (HR 0.32 (0.13–0.77)) and higher risk of major bleeding (HR 2.86 (1.49–5.50)) in patients with moderate to severe renal impairment (figure 1 and 2). Conclusion In patients with normal renal function, non-recommended low dose rivaroxaban was associated with increased cardiovascular mortality without reducing the risk of major bleeding compared to recommended dosing. In patients with CrCl &lt;50 ml/min, non-recommended high dose rivaroxaban was associated with reduced cardiovascular mortality but at the cost of increased major bleeding. These observational data largely support the reduction of rivaroxaban dosing according to renal function but educational strategies are needed to ensure that rivaroxaban is used appropriately. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the RIVER registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

scholarly journals Obesity and Recurrent Vascular Risk After a Recent Ischemic Stroke

Stroke ◽  
2011 ◽  
Vol 42 (12) ◽  
pp. 3397-3402 ◽  
Author(s):  
Bruce Ovbiagele ◽  
Philip M. Bath ◽  
Daniel Cotton ◽  
Richard Vinisko ◽  
Hans-Christoph Diener
Keyword(s):  
Ischemic Stroke ◽  
Stroke Risk ◽  
Recurrent Stroke ◽  
Obesity Paradox ◽  
Multicenter Trial ◽  
Hazard Ratio ◽  
Secondary Outcome ◽  
Vascular Risk ◽  
Established Risk Factor ◽  
The Impact

Background and Purpose— Although obesity is an established risk factor for the occurrence of a primary stroke, little is known about the impact of baseline obesity on recurrent vascular risk among patients with recently symptomatic cerebrovascular disease. We evaluated the association of obesity with future vascular risk in patients with a recent history of stroke. Methods— We analyzed the database of a multicenter trial involving 20 332 patients with recent ischemic stroke followed for 2.5 years. Subjects were divided into 3 groups according to recognized body mass index categories representing lean, overweight, and obese. Primary outcome was time to first recurrent stroke and secondary outcome time to stroke, myocardial infarction, or vascular death. The independent association of obesity with outcome was assessed by controlling for other known risk factors. Results— Of 20 246 eligible subjects, 4805 (24%) were obese. After adjusting for confounders, compared with the lean group, being overweight (hazard ratio, 0.95; 95% CI, 0.85–1.06) or obese (hazard ratio, 0.95; 95% CI, 0.83–1.08) was not associated with increased recurrent stroke risk, but being overweight (hazard ratio, 0.84; 95% CI, 0.77–0.92) or obese (hazard ratio, 0.86; 95% CI, 0.77–0.96) was associated with lower risk of a major vascular event. Conclusions— Obesity is not related to recurrent stroke risk, but obese patients with stroke are at lower overall vascular risk than their leaner counterparts, supporting the widely held notion of the existence of a cardiovascular “obesity paradox.”

Adherence to Antithrombotic Treatment and Ischemic Stroke Recurrence in Egypt and Germany: A Comparative Analysis

2021 ◽  
pp. 1-8
Author(s):  
Hazem Kamal ◽  
Mohamed Khodery ◽  
Hassan Elnady ◽  
Ahmed Borai ◽  
Jan Hendrik Schaefer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Recurrent Stroke ◽  
Developed Countries ◽  
Stroke Recurrence ◽  
Antithrombotic Treatment ◽  
Stroke Subtype ◽  
Recurrence Rates ◽  
Vessel Occlusion ◽  
The Impact ◽  
Time Point

<b><i>Background:</i></b> The burden of stroke weighs heavily in developing countries where recurrence rates clearly exceed that of developed countries. The impact of nonadherence to antithrombotic treatment within this context has been poorly investigated. <b><i>Objective:</i></b> The objective of this study was to evaluate patients with recurrent ischemic stroke in Egypt and Germany with focus on stroke subtype distribution and adherence to antithrombotic therapy. <b><i>Methods:</i></b> We conducted a comparative cross-sectional retrospective cohort study enrolling consecutive patients hospitalized for recurrent ischemic stroke in 2017 in 2 academic centers. Data were collected on demographics, risk factors, stroke subtypes, and medication adherence. Nonadherence to antithrombotic agents was analyzed at the time point of index stroke (recurrent stroke). Predictors of nonadherence were analyzed using logistic regression. <b><i>Results:</i></b> A total of 373 Egyptian and 468 German patients with ischemic stroke were included. The proportion of recurrent ischemic stroke among all patients was higher in the Egyptian cohort compared to the German cohort (33 vs. 10%, <i>p</i> &#x3c; 0.05). Small-vessel occlusion stroke was the most frequent subtype in Egyptians, with a significantly greater proportion than in Germans (45 vs. 26%, <i>p</i> &#x3c; 0.05). Nonadherence to antiplatelets at the time point of the recurrent stroke was higher in Egyptians than in Germans (82 vs. 19%, <i>p</i> &#x3c; 0.001). Low educational attainment among Egyptians (OR 0.14, 95% CI [0.00–0.19], <i>p</i> &#x3c; 0.01) and high comorbidity scores among Germans (OR 2.45, 95% CI [1.06–5.66], <i>p</i> &#x3c; 0.05) were found to be predictors of nonadherence to antithrombotic treatment. <b><i>Conclusions:</i></b> The large stroke recurrence burden in Egypt may be partly explained by differing adherence to secondary preventative antithrombotic pharmacotherapy. Predictors of medication nonadherence have to be addressed to reduce stroke recurrence disparities.

scholarly journals d -dimer Level as a Predictor of Recurrent Stroke in Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2021 ◽  
Author(s):  
Kang-Ho Choi ◽  
Ja-Hae Kim ◽  
Jae-Myung Kim ◽  
Kyung-Wook Kang ◽  
Changho Lee ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Recurrent Stroke ◽  
Primary Outcome Measure ◽  
Hazard Ratio ◽  
Embolic Stroke ◽  
Normal Range ◽  
Stroke Event ◽  
Increased Risk ◽  
Underlying Causes ◽  
Recurrent Strokes

Background and Purpose: This study aimed to investigate the value of d -dimer levels in predicting recurrent stroke in patients with embolic stroke of undetermined source. We also evaluated the underlying causes of recurrent stroke according to d -dimer levels. Methods: A total of 1431 patients with undetermined source were enrolled in this study and divided into quartiles according to their baseline plasma d -dimer levels. The primary outcome measure was the occurrence of recurrent stroke (ischemic or hemorrhagic) in the year following the stroke event. Results: The risk of recurrent stroke increased significantly with the increasing d -dimer quartile (log-rank P =0.001). Patients in the higher d -dimer quartiles had a higher probability of recurrent embolic stroke because of covert atrial fibrillation, hidden malignancy, or undetermined sources. Most recurrent strokes in Q3 and Q4 were embolic but not in Q1 or Q2. Multivariate analysis revealed that patients in Q3 and Q4 had a significantly increased risk of recurrent stroke compared with those in Q1 (hazard ratio, 3.12 [95% CI, 1.07−9.07], P =0.036; hazard ratio, 7.29 [95% CI, 2.59−20.52], P <0.001, respectively; P trend <0.001). Binary analyses showed a significant association between a high d -dimer level above normal range and the risk of recurrent stroke (hazard ratio, 2.48 [95% CI, 1.31−4.70], P =0.005). In subgroup analyses, a high d -dimer level was associated with a significantly higher risk of recurrent stroke in men than in women ( P =0.039). Conclusions: Our findings suggest that d -dimer levels can be a useful risk assessment biomarker for predicting recurrent stroke, especially embolic ischemic stroke, in patients with undetermined source.

scholarly journals Novel Oral Anticoagulants

2010 ◽  
Vol 113 (3) ◽  
pp. 726-745 ◽  
Author(s):  
Jerrold H. Levy ◽  
Nigel S. Key ◽  
Marc S. Azran
Keyword(s):  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Clinical Development ◽  
Thrombin Inhibitor ◽  
Potential Cost ◽  
Replacement Surgery ◽  
Postoperative Setting ◽  
Newer Anticoagulants ◽  
The Impact

Patients undergoing surgery receive anticoagulation for perioperative thromboprophylaxis or ischemic cardiovascular disease. Because anticoagulants may also potentiate bleeding, clinicians need to understand the implications of anticoagulation in perioperative and postoperative patient management. Many newer anticoagulants that are now available or are in clinical development do not require routine coagulation monitoring, have more predictable dose responses, and have fewer interactions with other drugs and food. The most advanced oral anticoagulants in clinical development are the direct factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran etexilate. These agents have been evaluated in the postoperative setting in patients undergoing total hip- or knee-replacement surgery with promising results, and it remains to be seen whether these results will translate into other surgical settings. The impact of the new agents will be influenced by the balance between efficacy and safety, improved convenience, and potential cost-effectiveness benefits.

scholarly journals Reevaluation of risk factors for time to subsequent events after first stroke occurrence using a new weighted all-cause effect measure

2020 ◽  
Author(s):  
Ann-Kathrin Ozga ◽  
Bernhard Rauch ◽  
Frederick Palm ◽  
Christian Urbanek ◽  
Armin Grau ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Recurrent Stroke ◽  
Treatment Options ◽  
Composite Endpoint ◽  
Hazard Ratio ◽  
Variable Degree ◽  
One Year ◽  
The Impact

Abstract Background: Risk diseases and risk factors for stroke include atrial fibrillation, hypertension, diabetes mellitus, smoking, and elevated LDL-cholesterol. Due to modern treatment options, the impact of these risk diseases on subsequent cardiovascular events or death after a first stroke is less clear and needs to be elucidated. We therefore aimed to get insights into the persistence of adverse prognostic effects of these risk diseases and risk factors on subsequent stroke or death events one year after the first stroke by using the new weighted all-cause hazard ratio.Methods: This study evaluates the one year follow-up of 470 first ever stroke cases identified in the area of Ludwigshafen, Germany, with 23 deaths and 34 subsequent stroke events. For this purpose, the recently introduced “weighted all-cause hazard ratio” was used, which allows a weighting of the competing endpoints within a composite endpoint. Moreover, we extended this approach to allow an adjustment for covariates. Results: None of these risk factors and risk diseases, most probably being treated after the first stroke, remained to be associated with a subsequent death or stroke [weighted hazard ratios (95% confidence interval) for diabetes mellitus, atrial fibrillation, high cholesterol, hypertension, and smoking are 0.4 (0.2 - 0.9), 0.8 (0.4 - 2.2), 1.3 (0.5 - 2.5), 1.2 (0.3 - 2.7), 1.6 (0.8 - 3.6), respectively]. However, when analyzed separately in terms of death and stroke, the risk factors and risk diseases under investigation affect the subsequent event rate to a variable degree.Conclusions: Using the new weighted hazard ratio, established risk factors and risk diseases for the occurrence of a first stroke do not remain to be significant predictors for subsequent events like death or recurrent stroke. It has been demonstrated that the new weighted hazard ratio can be used for a more adequate analysis of cardiovascular risk and disease progress. The results have to be confirmed within a larger study with more events.

Aspirin After Oral Anticoagulants for Prevention of Recurrence in Patients with Unprovoked Venous Thromboembolism. the Warfasa STUDY

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 543-543 ◽  
Author(s):  
Cecilia Becattini ◽  
Giancarlo Agnelli ◽  
Renzo Poggio ◽  
Sabine Eichinger ◽  
Eugenio Bucherini ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Conflicts Of Interest ◽  
Low Cost ◽  
Oral Anticoagulants ◽  
Hazard Ratio ◽  
Anticoagulant Treatment ◽  
Double Blind ◽  
Oral Anticoagulant Treatment

Abstract Abstract 543 Background A recurrence occurs in 15–20% of patients with unprovoked venous thromboembolism (VTE) in the two years after the withdrawal of oral anticoagulant treatment. Extending anticoagulant treatment is effective but associated with increased bleeding risk. We assessed the efficacy and safety of aspirin for the prevention of VTE recurrence after a conventional course of oral anticoagulation. Methods Warfasa was an investigator-initiated double-blind randomized placebo-controlled event-driven study. Patients with a first-ever unprovoked VTE who had completed 6–12 months of oral anticoagulant treatment were randomized to receive aspirin, 100 mg daily, or placebo for at least two years. The primary efficacy outcome was objectively confirmed recurrent symptomatic VTE and VTE-related death. Clinically relevant (major and non-major) bleeding were the main safety outcome. All outcome events were blindly adjudicated by an independent committee. Results A VTE recurrence occurred in 27 of the 205 patients who received aspirin and 42 of the 197 patients who received placebo (6.3% versus 11.0% patient-years; hazard ratio, 0.57, 95% CI 0.35 to 0.93) during the study period (mean 24 months) (Figure A). While on study treatment, 22 and 38 patients who received aspirin or placebo, respectively had a recurrence (5.7% versus 10.7% patient-years; hazard ratio, 0.54, 95% CI 0.32 to 0.91) (mean on-treatment period 22 months) (Figure B). One patient in each treatment group had a major bleeding, with a similar incidence of clinically relevant non-major bleeding. Conclusions Aspirin reduces by about 40% the risk of recurrence in patients with unprovoked VTE without increasing bleeding, when given after a 6–12 month anticoagulant treatment. For its safety, practicality and low cost, aspirin is a valid alternative to oral anticoagulants in the extended treatment of VTE. Disclosures: No relevant conflicts of interest to declare.

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