Design of Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate vs. Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (Re-Spect Esus)

2015 ◽  
Vol 10 (8) ◽  
pp. 1309-1312 ◽  
Author(s):  
Hans-Christoph Diener ◽  
J. Donald Easton ◽  
Christopher B. Granger ◽  
Lisa Cronin ◽  
Christine Duffy ◽  
...  
Keyword(s):  
Acetylsalicylic Acid ◽  
Stroke Prevention ◽  
Dabigatran Etexilate ◽  
Embolic Stroke ◽  
Thrombin Inhibitor ◽  
Secondary Stroke Prevention ◽  
Efficacy And Safety ◽  
Double Blind

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.

A single centre experience of the efficacy and safety of dabigatran etexilate used for stroke prevention in atrial fibrillation

2013 ◽  
Vol 38 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Lok Bin Yap ◽  
Beni Isman Rusani ◽  
Dhanan Umadevan ◽  
Zulkeflee Muhammad ◽  
Azlan Hussin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Dabigatran Etexilate ◽  
Efficacy And Safety ◽  
Single Centre ◽  
Single Centre Experience

Efficacy and Safety of Metamizol vs. Acetylsalicylic Acid in Patients With Moderate Episodic Tension-Type Headache: A Randomized, Double-Blind, Placebo- and Active-Controlled, Multicentre Study

Cephalalgia ◽  
2001 ◽  
Vol 21 (5) ◽  
pp. 604-610 ◽  
Author(s):  
P Martínez-Martín ◽  
E Raffaelli ◽  
F Titus ◽  
J Despuig ◽  
YD Fragoso ◽  
...  
Keyword(s):  
Pain Relief ◽  
Acetylsalicylic Acid ◽  
Pain Intensity ◽  
Pain Reduction ◽  
Tension Type Headache ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Maximum Pain ◽  
Type Headache

We assessed the efficacy and safety of oral single doses of 0.5 and 1 g metamizol vs. 1 g acetylsalicylic acid (ASA) in 417 patients with moderate episodic tension-type headache included in a randomized, double-blind, placebo- and active-controlled, parallel, multicentre trial. Eligibility criteria included 18–65 years of age, history of at least two episodes of tension-type headache per month in the 3 months prior to enrolment, and successful previous pain relief with a non-opioid analgesic. Treatment arms were metamizol 0.5 g ( n = 102), metamizol 1 g ( n = 108), ASA 1 g ( n = 102) and placebo ( n = 105). The analgesic efficacy of 0.5 and 1 g metamizol vs. placebo was highly statistically significant (α: 0.025; one-sided) for sum of pain intensity differences, maximum pain intensity difference, number of patients with at least 50% pain reduction, time to 50% pain reduction, maximum pain relief and total pain relief. A trend towards an earlier onset of a more profound pain relief of 0.5 and 1 g metamizol over 1 g ASA was noticed. All medications including placebo were almost equally safe and well tolerated.

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.

Abstract 13293: Detection of Atrial Fibrillation by Implantable Loop Recorders Following Cryptogenic Stroke: A Retrospective Study of Predictive Factors and Outcomes

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sara Samaan ◽  
Beshoy Nazeer ◽  
Heidi Stoute ◽  
Wei Zhao ◽  
Susanna Szpunar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Multivariable Analysis ◽  
Cryptogenic Stroke ◽  
Embolic Stroke ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Recurrence Rates ◽  
Implantable Loop Recorders

Introduction: Cryptogenic strokes account for up to 40% of ischemic strokes. Atrial fibrillation (AF) is a known cause of ischemic stroke. Current data shows that occult AF can be detected by implantable devices at higher rates than conventional cardiac rhythm monitoring. There are, however, limited data available on risk factors and outcomes associated with AF detection by implantable loop recorders (ILRs). Objective: To investigate the risk factors and outcomes associated with occult AF detected by ILR in patients with cryptogenic stroke. Methods: We conducted a retrospective chart review of patients admitted with cryptogenic stroke at Ascension St John Hospital and Ascension Macomb-Oakland Hospital in Michigan who had ILRs placed from 1/1/2016 to 1/31/2020. Data were collected on demographics, comorbidities, treatment and outcomes. AF detection was defined as continuous AF for 30 seconds. Data were analyzed using Student’s t-test, the χ2 test and logistic regression. Results: We reviewed 172 patients, 52.3% male, 56.4% white, mean age 62.7 ± 13.6 years. The incidence of AF detection by ILR was 14% (24/172) over a mean follow-up of 12.75 ± 10.71 months. The mean duration of monitoring prior to AF detection was 4.5 months (range:1 day to 14 months). The median duration of AF was 6 minutes (range: 37.2 seconds to 11.3 hours). From univariable analysis, older age (p=0.03), male sex (p=0.09), embolic stroke pattern on imaging (p=0.06), and lack of AF symptoms (p=0.001) were associated with AF detection by ILR. From multivariable analysis, patients with detected AF were more likely to be older (OR=1.04, p=0.04), male (OR=3.6, p=0.03), asymptomatic (OR=6.3, p=0.01), and have an embolic stroke pattern on imaging (OR=3.3, p=0.04). 95.7% of patients with confirmed AF were started on anticoagulation for secondary stroke prevention. There was no difference in the incidence of stroke post-hospitalization between those with AF detection and those without (16% vs. 16.4%, p=0.96). Conclusions: In patients with cryptogenic stroke, age, gender, stroke pattern, and lack of AF symptoms are independent predictors of occult AF detection by ILR. Most patients with confirmed AF were started on anticoagulation for secondary stroke prevention and had low stroke recurrence rates.

Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation

2014 ◽  
Vol 111 (05) ◽  
pp. 981-988 ◽  
Author(s):  
Torben Larsen ◽  
Lars Rasmussen ◽  
Gregory Y. H. Lip ◽  
Flemming Skjøth
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Ischaemic Stroke ◽  
Major Bleeding ◽  
Stroke Prevention ◽  
Dabigatran Etexilate ◽  
Indirect Comparison ◽  
High Dose ◽  
Efficacy And Safety ◽  
Comparison Analysis

SummaryLarge Phase 3 clinical trials for stroke prevention in atrial fibrillation (AF) have compared non-vitamin K antagonist oral anticoagulants (NOACs) against warfarin, with the edoxaban trial only recently reported. In the absence of head to head trials directly comparing these NOACs against each other, we compared the efficacy and safety of edoxaban to other agents by an indirect comparison analysis. We performed an indirect comparison analysis of edoxaban (2 dose strategies) against apixaban (1 dose), dabigatran etexilate (2 doses) and rivaroxaban (1 dose), for their relative efficacy and safety against each other. For high-dose edoxaban vs apixaban, there were no significant differences in efficacy endpoints, mortality, myocardial infarction and major bleeding. Apixaban was associated with less major or clinically relevant non-major bleeding (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70–0.90) and gastrointestinal bleeding (HR 0.72; 95% CI 0.53–0.99). For dabigatran 110 mg twice daily, there were no significant differences in the main efficacy or safety endpoints. Dabigatran 150 mg bid was associated with lower stroke/systemic embolism (SE) (HR 0.75; 95% CI 0.56–0.99), stroke (HR 0.73; 95% CI 0.55–0.96) and haemorrhagic stroke (HR 0.48; 95% CI 0.23–0.99). There were no significant differences between high-dose edoxaban vs rivaroxaban for efficacy endpoints or mortality, but rivaroxaban had more major and/or clinically relevant non-major bleeding. When compared to low-dose edoxaban, apixaban was associated with lower stroke/SE (HR 0.70; 95% CI 0.55–0.89), stroke (HR 0.70; 95% CI 0.55–0.92) and ischaemic stroke (HR 0.65; 95% CI 0.50–0.89), but more major bleeding (HR 1.47; 95% CI 1.20–1.80). For dabigatran 110 mg bid, there were no significant differences in the efficacy endpoints, but dabigatran 110 mg bid had higher major (and gastrointestinal) bleeding. Dabigatran 150 mg bid and rivaroxaban were associated with lower stroke/SE and ischaemic stroke, but higher bleeding rates. In the present analysis, we have provided for the first time, comparisons of efficacy and safety of edoxaban against other NOACs. Notwithstanding the significant limitations of an indirect comparison analysis, some differential effects are evident with the NOACs for stroke prevention, allowing us to allow the prescriber a ‘choice’ to be able to fit the drug to the patient clinical profile (and vice versa).Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

Dabigatran for stroke prevention in atrial fibrillation

2012 ◽  
Vol 32 (03) ◽  
pp. 216-220 ◽  
Author(s):  
H.-C. Diener ◽  
S. H. Hohnloser
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Relative Risk Reduction ◽  
Haemorrhagic Stroke ◽  
Similar Rate ◽  
Thrombin Inhibitor ◽  
Secondary Stroke Prevention ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Low Incidence

SummaryDabigatran is a novel direct thrombin inhibitor that has recently been approved for primary and secondary stroke prevention and prevention of systemic embolism in patients with atrial fibrillation. In the pivotal RE-LY study, dabigatran 110 mg BID was demonstrated to be associated with a stroke rate similar to that observed with warfarin (INR target 2.0 to 3.0), but with a lower rate of major haemorrhage. Dabigatran administered at a dose of 150 mg BID was significantly more effective in stroke prevention than warfarin and showed a similar rate of major hemorrhages. Of note, both dosages resulted in an approximately 60–70% relative risk reduction of haemorrhagic stroke. The dosage of 110 mg BID should be preferably used in patients aged 75–80 years or older as the rate of extracranial bleeding events tends to increase with dabigatran 150 mg BID above this age limit. In RE-LY, myocardial infarcts occurred at a very low incidence. There were numerically more myocardial infarcts in dabigatran-treated patients than in warfarin patients; however, other myocardial ischaemic events were similar in the three treatment arms.

scholarly journals Dabigatran for Stroke Prevention in Nonvalvular Atrial Fibrillation: Answers to Challenging “Real-World” Questions

Thrombosis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jorge Ferreira ◽  
Daniel Ferreira ◽  
Miguel Viana-Baptista ◽  
Paulo Bettencourt ◽  
Rui Cernadas ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Real World ◽  
Stroke Prevention ◽  
Oral Anticoagulant ◽  
Dabigatran Etexilate ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitor ◽  
Joint Effort ◽  
Nonvalvular Atrial Fibrillation ◽  
New Oral Anticoagulant

Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral anticoagulant approved in Europe and became available in Portugal, for stroke prevention in nonvalvular AF, earlier than in most European countries. This paper is the joint effort of a panel of experts from different specialties and provides information on the use of dabigatran, in anticipation of the challenges that will come with increased usage.

scholarly journals Secondary Stroke Prevention Following Embolic Stroke of Unknown Source in the Absence of Documented Atrial Fibrillation: A Clinical Review

2021 ◽  
Author(s):  
Irum D. Kotadia ◽  
Iain Sim ◽  
Rahul Mukherjee ◽  
Daniel O’Hare ◽  
Amedeo Chiribiri ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Structural Changes ◽  
Stroke Risk ◽  
Cryptogenic Stroke ◽  
Embolic Stroke ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Unknown Source ◽  
The Relationship

Abstract Approximately one‐third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one‐third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.

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