scholarly journals Atrial fibrillation and stroke: a practical guide

2019 ◽  
Vol 19 (3) ◽  
pp. 208-224 ◽  
Author(s):  
Jonathan Gordon Best ◽  
Robert Bell ◽  
Mohammed Haque ◽  
Arvind Chandratheva ◽  
David John Werring
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Interdisciplinary Collaboration ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Stroke Care ◽  
Evidence Base ◽  
Ongoing Research ◽  
Widespread Availability ◽  
Difficult Area

Neurologists and stroke physicians will be familiar with atrial fibrillation as a major cause of ischaemic stroke, and the role of anticoagulation in preventing cardioembolic stroke. However, making decisions about anticoagulation for individual patients remains a difficult area of clinical practice, balancing the serious risk of ischaemic stroke against that of major bleeding, particularly intracranial haemorrhage. Atrial fibrillation management requires interdisciplinary collaboration with colleagues in cardiology and haematology. Recent advances, especially the now-widespread availability of direct oral anticoagulants, have brought opportunities to improve stroke care while posing new challenges. This article gives an overview of the contemporary diagnosis and management of atrial fibrillation, and the associated evidence base. Where there is uncertainty, we describe our own approach to these areas, while highlighting ongoing research that will likely guide future practice.

scholarly journals The Oral Anticoagulants Administration in Elderly Patients with Geriatric Syndromes: What's New?

2020 ◽  
Vol 16 (6) ◽  
pp. 984-993
Author(s):  
N. M. Vorobyeva ◽  
O. N. Tkacheva
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
The Elderly ◽  
Evidence Base ◽  
Geriatric Syndromes ◽  
Consensus Document ◽  
Venous Thromboembolic ◽  
Risk Of Falls

The administration of oral anticoagulants in elderly patients with geriatric syndromes such as senile asthenia syndrome, falls and high risk of falls, dementia, polymorbidity, polypharmacy are discussed in the article. The evidence base for the anticoagulants taking in patients with atrial fibrillation aged ≥75, ≥80, ≥85 and ≥90 years, in patients with atrial fibrillation and various geriatric syndromes, as well as in elderly patients with venous thromboembolic complications and frailty syndrome is presented. Most studies indicate significant advantages of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) over the vitamin K antagonist warfarin in elderly patients with geriatric syndromes. An updated version of the FORTA consensus document, which aims to optimize the prescription of medicines for the elderly, is also presented. Apixaban has a FORTA-A safety class and is the safest oral anticoagulant in elderly patients.

scholarly journals Clinical and budget impacts of changes in oral anticoagulation prescribing for atrial fibrillation

Heart ◽  
2020 ◽  
Vol 107 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Andi Orlowski ◽  
Chris P Gale ◽  
Rachel Ashton ◽  
Bruno Petrungaro ◽  
Ruth Slater ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
National Level ◽  
Stroke Care ◽  
Published Data ◽  
Stroke Incidence ◽  
Number Of Patients ◽  
National Databases

ObjectiveTo assess temporal clinical and budget impacts of changes in atrial fibrillation (AF)-related prescribing in England.MethodsData on AF prevalence, AF-related stroke incidence and prescribing for all National Health Service general practices, hospitals and registered patients with hospitalised AF-related stroke in England were obtained from national databases. Stroke care costs were based on published data. We compared changes in oral anticoagulation prescribing (warfarin or direct oral anticoagulants (DOACs)), incidence of hospitalised AF-related stroke, and associated overall and per-patient costs in the periods January 2011–June 2014 and July 2014–December 2017.ResultsBetween 2011–2014 and 2014–2017, recipients of oral anticoagulation for AF increased by 86.5% from 1 381 170 to 2 575 669. The number of patients prescribed warfarin grew by 16.1% from 1 313 544 to 1 525 674 and those taking DOACs by 1452.7% from 67 626 to 1 049 995. Prescribed items increased by 5.9% for warfarin (95% CI 2.9% to 8.9%) but by 2004.8% for DOACs (95% CI 1848.8% to 2160.7%). Oral anticoagulation prescription cost rose overall by 781.2%, from £87 313 310 to £769 444 028, (£733,466,204 with warfarin monitoring) and per patient by 50.7%, from £293 to £442, giving an incremental cost of £149. Nevertheless, as AF-related stroke incidence fell by 11.3% (95% CI −11.5% to −11.1%) from 86 467 in 2011–2014 to 76 730 in 2014–2017 with adjustment for AF prevalence, the overall per-patient cost reduced from £1129 to £840, giving an incremental per-patient saving of £289.ConclusionsDespite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke led to incremental savings at the national level.

scholarly journals Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Klaus K. Witte ◽  
Georgios Tsivgoulis ◽  
Matthew R. Reynolds ◽  
Stelios I. Tsintzos ◽  
Simon Eggington ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Recurrent Stroke ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Event ◽  
Cost Savings ◽  
Embolic Stroke ◽  
Bleeding Events ◽  
Event Rates

Abstract Objective Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. Methods CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. Results Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient’s lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953–£7018 per patient (UK), €6683–€7368 (Netherlands), €4933–€9378 (Spain), AUD$5353–6539 (Australia) and $26,768–$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468–$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). Conclusions Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

scholarly journals 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

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.

scholarly journals Effectiveness and Safety of Direct Oral Anticoagulants versus Vitamin K Antagonists for People Aged 75 Years and over with Atrial Fibrillation: A Systematic Review and Meta-Analyses of Observational Studies

2019 ◽  
Vol 8 (4) ◽  
pp. 554 ◽  
Author(s):  
Anneka Mitchell ◽  
Margaret C. Watson ◽  
Tomas Welsh ◽  
Anita McGrogan
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Major Bleeding ◽  
Observational Studies ◽  
Intracranial Haemorrhage ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Difference ◽  
Meta Analyses

Older people, are underrepresented in randomised controlled trials of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to combine data from observational studies to provide evidence for the treatment of people aged ≥75 years. Medline, Embase, Scopus and Web of Science were searched. The primary effectiveness outcome was ischaemic stroke. Safety outcomes were major bleeding, intracranial haemorrhage, gastrointestinal bleeding, myocardial infarction, and mortality. Twenty-two studies were eligible for inclusion. Two studies related specifically to people ≥75 years but were excluded from meta-analysis due to low quality; all data in the meta-analyses were from subgroups. The pooled risk estimate of ischaemic stroke was slightly lower for DOACs. There was no significant difference in major bleeding, mortality, or myocardial infarction. Risk of intracranial haemorrhage was 44% lower with DOACs, but risk of GI bleeding was 46% higher. Our results suggest that DOACs may be preferable for the majority of older patients with AF, provided they are not at significant risk of a GI bleed. However, these results are based entirely on data from subgroup analyses so should be interpreted cautiously. There is a need for adequately powered research in this patient group.

scholarly journals Burden of Oral Anticoagulation in Embolic Stroke of Undetermined Source without Atrial Fibrillation

2021 ◽  
Author(s):  
Klaus Witte ◽  
Georgios Tsivgoulis ◽  
Matthew Reynolds ◽  
Stelios Tsintzos ◽  
Simon Eggington ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Recurrent Stroke ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Event ◽  
Cost Savings ◽  
Embolic Stroke ◽  
Bleeding Events ◽  
Event Rates

Abstract Objective: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies.Methods: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective.Results: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient’s lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5,953-£7,018 per patient (UK), €6,683-€7,368 (Netherlands), €4,933-€9,378 (Spain), AUD$5,353-6,539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $1,716-$12,473 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years).Conclusions: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

Unanswered questions and research priorities to optimise stroke prevention in atrial fibrillation with the new oral anticoagulants

2014 ◽  
Vol 111 (05) ◽  
pp. 808-816 ◽  
Author(s):  
Graeme J. Hankey
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Stroke Prevention ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Research Priorities ◽  
Fixed Dose ◽  
Optimal Time ◽  
Prosthetic Heart Valves

SummaryThis review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and stroke prevention in atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In patients prescribed a NOAC, can the anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can “cut-off points” between which anticoagulation is therapeutic (i.e. the “therapeutic range”) be defined? 2. In patients who are taking a NOAC and bleeding (e.g. intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can NOAC-associated bleeding and complications be minimised and patient outcome improved? 3. In patients taking a NOAC who experience an acute ischaemic stroke, to what degree of anticoagulation or plasma concentration of NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a NOAC (or warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have atrial fibrillation and are at high risk of stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is there a dose or dosing regimen for each NOAC that is as effective and safe as adjusted-dose warfarin for patients with atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?

scholarly journals A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

2021 ◽  
Vol 10 (13) ◽  
pp. 2924
Author(s):  
Domenico Acanfora ◽  
Marco Matteo Ciccone ◽  
Valentina Carlomagno ◽  
Pietro Scicchitano ◽  
Chiara Acanfora ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Risk Index ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Efficacy Rate ◽  
Cochrane Central Register ◽  
Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

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