Rationale, Design and Methods of the Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) Study

2021 ◽  
pp. 239698732110602
Author(s):  
Gerrit M. Grosse ◽  
Christian Weimar ◽  
Nils Kuklik ◽  
Anika Hüsing ◽  
Andreas Stang ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Acute Stroke ◽  
Antithrombotic Therapy ◽  
Vitamin K Antagonists ◽  
Optimal Time ◽  
Optimal Timing ◽  
Real World Data ◽  
Index Event ◽  
Increased Risk ◽  
Design And Methods

Background The optimal timing of anticoagulation following acute ischaemic stroke or TIA in patients with atrial fibrillation (AF) is a frequent challenge. Early initiation of anticoagulation can reduce the risk for recurrent ischaemic events, but may lead to an increased risk for intracerebral haemorrhage. Aim The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study was initiated to investigate outcome events under antithrombotic therapy after ischaemic stroke or TIA in patients with AF. The main objective is to compare the three-month rates of major haemorrhagic events between early (≤ 7 days) versus late (> 7 days) administration of dabigatran or treatment with vitamin-K antagonists started at any time. Occurrences of ischaemic and major haemorrhagic events will be evaluated to determine the optimal time point for initiation or resumption of anticoagulation. Design and Methods PRODAST is a prospective, multicenter, observational, non-interventional post-authorization safety study. 10,000 patients with recent (≤ 1 week from index event) ischaemic stroke or TIA and non-valvular AF were recruited at 86 German sites starting in July 2015. The observational plan includes a baseline visit, documentation of data during hospitalization and a telephone-based, central follow-up at three months after the index event. The primary endpoint is the major bleeding rate within three months. Secondary endpoints include rates of recurrent ischaemic or haemorrhagic stroke, TIA, systemic embolism, myocardial infarction and death. Summary PRODAST will provide important real-world data on safety and efficacy of antithrombotic therapy after acute stroke and TIA in patients with AF.

scholarly journals A Systematic Review and Meta-Analysis of Molecular Biomarkers Associated with Early Neurological Deterioration Following Acute Stroke

2018 ◽  
Vol 46 (5-6) ◽  
pp. 230-241 ◽  
Author(s):  
Alexander J. Martin ◽  
Christopher I. Price
Keyword(s):  
Ischaemic Stroke ◽  
Acute Stroke ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Neurological Status ◽  
Neurological Deterioration ◽  
Increased Risk ◽  
Early Neurological Deterioration

Background: Early neurological deterioration (END) following acute stroke is associated with poorer long-term outcomes. Identification of patients at risk could assist early monitoring and treatment decisions. This review summarised the evidence describing non-radiological biomarkers for END. Summary: Electronic searches from January 1990 to March 2017 identified studies reporting a blood/cerebrospinal fluid (CSF)/urine biomarker measurement within 24 h of acute stroke and at least 2 serial assessments of clinical neurological status (< 24 h and < 7 days). Out of 12,895 citations, 82 studies were included, mostly focusing on ischaemic stroke. Using higher neurological thresholds, the n-weighted END incidence for ischaemic stroke was 11.9% (95% CI 11.4–12.4%) and 18.6% (17.9–19.2%) for lower thresholds. Incidence decreased with advancing study publication year (Pearson r-squared 0.23 and 0.15 for higher and lower threshold studies). After classification into 3 broad categories, meta-analysis showed that biomarkers associated with increased END risk (n; fixed-effects mean difference; 95% CI) were “metabolic” (glucose [n = 9,481; 0.90 mmol/L; 0.74–1.06], glycosylated haemoglobin [n = 3,146; 0.33%; 0.19–0.46], low-density lipoprotein [n = 4,839; 0.13 mmol/L; 0.06–0.21], total cholesterol [n = 4,762; 0.21 mmol/L; 0.11–0.31], triglycerides [n = 4,820; 0.11 mmol/L; 0.06–0.17], urea [n = 1,351; 0.55 mmol/L; 0.14–0.96], decreasing albumin [n = 513; 0.33 g/dL; 0.05–0.61]); “inflammatory and excitotoxic” (plasma glutamate [n = 688; 60.13 µmol/L; 50.04–70.22], CSF glutamate [n = 369; 7.50 µmol/L; 6.76–8.23], homocysteine [n = 824; 2.15 µmol/L; 0.68–3.61], leucocytes [n = 3,766; 0.54 × 109/L; 0.34–0.74], high-sensitivity C-reactive protein [n = 1,707; 3.79 mg/L; 1.23–6.35]); and “coagulation/haematological” (fibrinogen [n = 3,132; 0.32 g/L; 0.25–0.40]; decreasing haemoglobin [n = 3,586; 2.38 g/L; 0.15–4.60]). Key Messages: Declining incidence of END may represent improving care standards; however, it remains a frequent occurrence. Although statistical associations exist between biomarkers and an increased risk of END, the most promising still need prospective evaluation to determine their additional value relative to baseline radiological and clinical characteristics.

Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding

2017 ◽  
Vol 117 (03) ◽  
pp. 491-499 ◽  
Author(s):  
Niklas Wallvik ◽  
Joakim Eriksson ◽  
Jonas Höijer ◽  
Matteo Bottai ◽  
Margareta Holmström ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Bleeding Event ◽  
Optimal Timing ◽  
Thromboembolic Events ◽  
Gi Bleeding ◽  
Upper Gi Bleeding ◽  
Upper Gi ◽  
Increased Risk ◽  
Upper Gastrointestinal

SummaryThe optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the ‘total risk’, based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58 %) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2–3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07–0.55) and death (HR 0.61; 95 % CI, 0.39–0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95 % CI, 1.4–4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3–6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

P1187Pocket-Hematoma after cardiac implantable electronic devices surgery: a single centre study

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
L Spighi ◽  
F Notaristefano ◽  
R Annunziata ◽  
M D"ammando ◽  
G Zingarini ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Antithrombotic Therapy ◽  
Pulse Generator ◽  
Dual Antiplatelet Therapy ◽  
Vitamin K Antagonists ◽  
Multivariate Regression Analysis ◽  
New Device ◽  
Increased Risk ◽  
The Impact ◽  
Pocket Hematoma

Abstract Intro Pocket hematoma is a common complication after pacemaker (PMK) or implantable cardioverter defibrillator (ICD) surgery. In this clinical setting anticoagulant and antiplatelet therapy are associated with an increased risk of hemorrhagic complications, but data are sparse. Purpose We examined  the impact of antiplatelet therapy and anticoagulation with vitamin K antagonists (VKA) or heparin on the risk of pocket hematoma. Materials and method: between august 2017 and june 2019, a total of 639 devices were implanted or replaced at our centre. Predictors of hematoma occurrence were determined by multivariate regression analysis. We used a specific definition of pocket hematoma: a) any palpable swelling in the pocket area requiring an unscheduled visit or prolonged hospitalization &gt; 24 h or re-hospitalization for hematoma, b) interruption of antithrombotics, c) reoperation, d) hemoglobin drop &gt; 2 g/dl or blood transfusion. The above criteria were assessed during hospitalization and up to 10 days after discharge. Results: the incidence of pocket hematoma was 7.5%. Among 639 patients (pts) including in the study 33.5% (214 pts) didn’ t take any antithrombotic therapy, 40.2 % (257 pts) were on single antiplatelet therapy (SAPT), 8.8 % (56 pts) were on dual antiplatelet therapy, 11.1 % (71 pts) were on uninterrupted VKA (mean INR 2). Heparin bridging was administered in 6.4% (41 pts). Ejection fraction (43 ±13 %) and  hemoglobin value before implantation (12.3 ±2.6 g/dL) in patients who developed hematoma were significantly lower compared with whose without hematoma. Patients with hematoma had a higher prevalence of congestive heart failure, ischemic cardiomyopathy and intake antithrombotic therapy. After adjusting for confounding factors with multivariate logistic regression only the use of dual antiplatelet therapy (OR 5.9 95% CI 1.5-21 p = 0.008) and the bridging with enoxaparin (OR 5.6 95% CI 1.4-22 p = 0.013) increased the risk of pocket hematoma. Single antiplatelet therapy (OR 2.6 95% CI 0.8-8.4 p = ns) and uninterrupted VKA (OR 0.9 95% CI 0.7-11 p = ns) did not increased the risk of pocket hematoma compared to no antithrombotic therapy. Pulse generator change and new device implant/upgrading (OR 1.8 95% CI 0.6-5.2 p = ns) carried the same haemorrhagic risk. Conclusion the use of DAPT or bridging with enoxaparin are highly predictive for the occurrence of perioperative pocket hematoma in patients scheduled for pmk/icd surgery. In contrast, single antiplatelet therapy and uninterrupted VKA  did not increase the risk of hematoma.

Timing of anticoagulation therapy in patients with acute ischaemic stroke and atrial fibrillation

2016 ◽  
Vol 116 (09) ◽  
pp. 410-416 ◽  
Author(s):  
Maurizio Paciaroni ◽  
Giancarlo Agnelli ◽  
Walter Ageno ◽  
Valeria Caso
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Substantial Reduction ◽  
Anticoagulation Therapy ◽  
Early Recurrence ◽  
Optimal Time ◽  
Optimal Timing ◽  
Stroke Patients ◽  
Haemorrhagic Transformation

SummaryIn patients with acute stroke and atrial fibrillation (AF), the risk of early recurrence has been reported to range between 0.1% and 1.3% per day. Anticoagulants are the most effective therapy for the prevention of recurrent ischaemic stroke in these patients, but randomised clinical trials have failed to produce any evidence supporting the administration of heparin within 48 hours from stroke onset as it has been associated with a non-significant reduction in the recurrence of ischaemic stroke, no substantial reduction in death and disability, and an increase in intracranial bleeding. As early haemorrhagic transformation is a major concern in the acute phase of stroke patients with AF, determining the optimal time to start anticoagulant therapy is essential. This review which focuses on the epidemiology of recurrent ischaemic stroke and haemorrhagic transformation in patients with acute ischaemic stroke and AF, proposes a model for decision making on optimal timing for initiating anticoagulation, based on currently available evidence.

scholarly journals Dabigatran initiation in patients with non-valvular AF and first acute ischaemic stroke: a retrospective observational study from the SITS registry

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e037234
Author(s):  
Irene Escudero-Martinez ◽  
Michael Mazya ◽  
Christine Teutsch ◽  
Norbert Lesko ◽  
Zuzana Gdovinova ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Clinical Outcomes ◽  
Acute Ischaemic Stroke ◽  
Demographic Data ◽  
Intravenous Thrombolysis ◽  
Optimal Timing ◽  
Stroke Severity ◽  
Stroke Index ◽  
Index Event ◽  
Registration Number

Background and objectiveThe optimal timing for initiation of dabigatran after acute ischaemic stroke (AIS) is not established. We aimed to evaluate initiation timing and clinical outcomes of dabigatran in AIS patients with non-valvular atrial fibrillation (NVAF).DesignRetrospective study based on prospectively collected data in SITS (Safe Implementation of Treatment in Stroke) Thrombolysis and Thrombectomy Registry from July 2014 to July 2018.ParticipantsEuropean NVAF patients (≥18 years) hospitalised after first-ever ischaemic stroke.SettingA multinational, observational monitoring register.InterventionDabigatran initiation within 3 months after the ischaemic stroke.Primary and secondary outcomesThe primary outcome was time from first-ever ischaemic stroke (index event) to dabigatran initiation. Additional outcomes included physicians’ reasons for delaying dabigatran initiation beyond acute hospital discharge and outcomes within 3 months of index event.MethodsWe identified patients with NVAF who received dabigatran within 3 months of the index event. We performed descriptive statistics for baseline and demographic data and clinical outcomes after dabigatran initiation.ResultsIn total, 1489 patients with NVAF received dabigatran after AIS treated with thrombolysis and/or thrombectomy. Of these, 1240 had available initiation time. At baseline, median age was 75 years; 53% of patients were women, 15% were receiving an oral anticoagulant, 29% acetylsalicylic acid and 4% clopidogrel. Most patients (82%) initiated dabigatran within 14 days after the index event. Patients initiating earlier had lower stroke severity from median NIHSS 8 (IQR 6–13) if initiated within 7 days to NIHSS 15 (9–19) if initiated between 28 days and 3 months. Most common reasons for delaying initiation were haemorrhagic transformation or intracranial haemorrhage, stroke severity and infarct size. Few thrombotic/haemorrhagic events occurred within 3 months after the index event (20 of 926 patients, 2.2% with the available data).ConclusionsOur findings, together with previous observational studies, indicate that dabigatran initiated within the first days after an AIS is safe in patients treated with intravenous thrombolysis, endovascular thrombectomy or both.Trial registration numberSITS Thrombolysis and Thrombectomy Registry (NCT03258645).

Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network

2021 ◽  
pp. 135245852110101
Author(s):  
Pietro Iaffaldano ◽  
Giuseppe Lucisano ◽  
Helmut Butzkueven ◽  
Jan Hillert ◽  
Robert Hyde ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cox Regression ◽  
Disease Onset ◽  
Optimal Time ◽  
Optimal Timing ◽  
Real World Data ◽  
Treatment Start ◽  
Time To First Treatment ◽  
The Impact

Background: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( p < 0.0004) for the first quintile patients’ group. Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.

scholarly journals 133 Incidence of Imaging Confirmed Stroke and Thrombotic Events in Older Adults with Severe COVID-19 Infection

2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
L Hickmott ◽  
C Jeyarajah ◽  
S Logarajah ◽  
A Webber ◽  
D Epstein ◽  
...  
Keyword(s):  
Older Adults ◽  
Ischaemic Stroke ◽  
Acute Stroke ◽  
Sinus Thrombosis ◽  
Local Population ◽  
Thrombotic Event ◽  
Clinical Signs ◽  
Cerebral Haemorrhage ◽  
Increased Risk ◽  
D Dimer

Abstract   During the initial phase of the response to COVID-19, concern was raised regarding a potential link with increased risk of stroke. We aimed to explore the incidence of stroke and thrombotic events within our local population with COVID-19 infection who required admission to the Intensive Care Unit (ICU). Methods Retrospective analysis of 57 consecutive patients with a diagnosis of COVID-19 infection admitted to Barnet General Hospital ICU between 6th March and 26th April 2020. Cases were reviewed to establish whether there had been imaging (CT or MRI) confirmed ischaemic stroke, intra-cerebral haemorrhage (ICH), venous sinus thrombosis (VST) or other thrombotic event, including pulmonary embolism (PE). Data was collected on baseline characteristics and blood tests including D-Dimer levels. Statistical analysis was performed using two-tailed t-test and Fischer’s exact test (FET). Findings: Nineteen patients (33%) were age 65 years or older (mean age 69, range 65 to 74 years) and of these 2 patients (10.5%) had imaging confirmed acute ischaemic stroke. In those under 65 (mean age 54, range 29–64 years) there was one confirmed ICH and one VST. The incidence of PE was 21% in both groups. Survival was significantly lower in the age 65 or older group (26.3% versus 63.2%, p = 0.0119 (FET)). Peak recorded D-Dimer levels also appeared to be significantly higher in the age 65 or older group (p = 0.0003, 95% CI 13068.89 to 39858.68). Conclusions and limitations These findings highlight the importance of awareness of risk of thrombotic events, including acute stroke, in older adults with severe Covid-19 infection. It is possible that the incidence of stroke was underestimated, including due to challenges identifying clinical signs of acute stroke and safely obtaining imaging in this population. Further, ideally prospective, studies are required to more clearly elucidate the degree of association between COVID-19 infection and stroke and VST.

Safety and efficacy of direct acting oral anticoagulants and vitamin K antagonists in nonvalvular atrial fibrillation – a network meta-analysis of real-world data

VASA ◽  
2019 ◽  
Vol 48 (2) ◽  
pp. 134-147 ◽  
Author(s):  
Mirko Hirschl ◽  
Michael Kundi
Keyword(s):  
Real World ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Nonvalvular Atrial Fibrillation ◽  
Real World Data ◽  
Hazard Ratios ◽  
Direct Acting ◽  
Event Rates

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.

Optimal Timing for Lung Transplantation: Why Not Include RVEF As an Indicator?

2012 ◽  
Vol 11 (1) ◽  
pp. 47-48
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Lung Transplantation ◽  
Severity Of Illness ◽  
Right Atrial ◽  
Optimal Time ◽  
Optimal Timing ◽  
Predictors Of Outcome ◽  
Donor Organ ◽  
Pulmonary Arterial ◽  
Rv Function

One of the most challenging questions to answer in pulmonary arterial hypertension (PAH) is: “When is the optimal time to proceed with lung transplantation?” The current lung allocation scoring (LAS) system prioritizes donor organ resources based on severity of illness. Factors used to assign LAS do not account for known predictors of outcome for PAH patients—including determinants of right ventricular (RV) function. It has been recognized that the system places PAH patients at a distinct disadvantage, and concerted efforts are being made to correct this by considering variables that reflect RV function, specifically mean right atrial pressure (mRAP) and cardiac index (CI).

Antithrombotic Therapy in Lower Extremity Artery Disease

2020 ◽  
Vol 18 (3) ◽  
pp. 215-222 ◽  
Author(s):  
Mislav Vrsalovic ◽  
Victor Aboyans
Keyword(s):  
Lower Extremity ◽  
Antiplatelet Therapy ◽  
Antithrombotic Therapy ◽  
Cardiovascular Events ◽  
Cardiovascular Outcomes ◽  
Lower Limbs ◽  
Stent Type ◽  
Increased Risk ◽  
Artery Disease ◽  
Lower Extremity Artery Disease

Lower extremity artery disease (LEAD) is a marker of a more advanced atherosclerotic process often affecting multiple vascular beds beyond the lower limbs, with a consequent increased risk for all-cause and cardiovascular mortality. Antithrombotic therapy is the cornerstone of management of these patients to prevent ischaemic cardiovascular and limb events and death. In patients with symptomatic LEAD, the efficacy of aspirin has been established long ago for the prevention of cardiovascular events. In the current guidelines, clopidogrel may be preferred over aspirin following its incremental ability to prevent cardiovascular events, while ticagrelor is not superior to clopidogrel in reducing cardiovascular outcomes. Dual antiplatelet therapy (DAPT, aspirin with clopidogrel) is currently recommended for at least 1 month after endovascular interventions irrespective of the stent type. Antiplatelet monotherapy is recommended after infra-inguinal bypass surgery, and DAPT may be considered in below-the-knee bypass with a prosthetic graft. In symptomatic LEAD, the addition of anticoagulant (vitamin K antagonists) to antiplatelet therapy increased the risk of major and life-threatening bleeding without benefit regarding cardiovascular outcomes. In a recent trial, low dose of direct oral anticoagulant rivaroxaban plus aspirin showed promising results, not only to reduce death and major cardiovascular events, but also major limb events including amputation. Yet, this option should be considered especially in very high risk patients, after considering also the bleeding risk. Despite all the evidence accumulated since >40 years, many patients with LEAD remain undertreated and deserve close attention and implementation of guidelines advocating the use of antithrombotic therapies, tailored according to their level of risk.

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