Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation

Slot, Karsten Mh Bruins; Berge, Eivind

doi:10.1002/14651858.cd008980.pub3

Cited by 38 publications

(22 citation statements)

References 68 publications

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“…Since 2010, four direct oral anti-coagulants (DOACs; ie, apixaban, 7 dabigatran, 8 edoxaban, 9 and rivaroxaban 10 ) have been approved for use in patients with non-valvular atrial fibrillation. Cochrane reviews and meta-analyses 11,12 found that these DOACs have similar efficacy to VKAs in primary and secondary prevention of stroke but are associated with about half the frequency of intracranial haemorrhage. However, none of the randomised controlled trials comparing DOACs and VKAs included patients with recent ischaemic stroke associated with atrial fibrillation (within the first few weeks)—presumably because of concerns about the risk of haemorrhagic trans formation of the ischaemic brain tissue or of other intracranial haemorrhage.…”

Section: Introductionmentioning

confidence: 99%

Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation

Seiffge

Werring

Paciaroni

et al. 2019

The Lancet Neurology

186

142

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Summary Background About 13–26% of all acute ischaemic strokes are related to non-valvular atrial fibrillation, the most common cardiac arrhythmia globally. Deciding when to initiate oral anticoagulation in patients with non-valvular atrial fibrillation is a longstanding, common, and unresolved clinical challenge. Although the risk of early recurrent ischaemic stroke is high in this population, early oral anticoagulation is suspected to increase the risk of potentially harmful intracranial haemorrhage, including haemorrhagic transformation of the infarct. This assumption, and current treatment guidelines, are based on historical, mostly observational data from patients with ischaemic stroke and atrial fibrillation treated with heparins, heparinoids, or vitamin K antagonists (VKAs) to prevent recurrent ischaemic stroke. Randomised controlled trials have subsequently shown that direct oral anticoagulants (DOACs; ie, apixaban, dabigatran, edoxaban, and rivaroxaban) are at least as effective as VKAs in primary and secondary prevention of atrial fibrillation-related ischaemic stroke, with around half the risk of intracranial haemorrhage. However, none of these DOAC trials included patients who had experienced ischaemic stroke recently (within the first few weeks). Clinicians therefore remain uncertain regarding when to commence DOAC administration after acute ischaemic stroke in patients with atrial fibrillation. Recent developments Prospective observational studies and two small randomised trials have investigated the risks and benefits of early DOAC-administration initiation (most with a median delay of 3–5 days) in mild-to-moderate atrial fibrillation-associated ischaemic stroke. These studies reported that early DOAC treatment was associated with a low frequency of clinically symptomatic intracranial haemorrhage or surrogate haemorrhagic lesions on MRI scans, whereas later DOAC-administration initiation (ie, >7 days or >14 days after index stroke) was associated with an increased frequency of recurrent ischaemic stroke. Where next? Adequately powered randomised controlled trials comparing early to later oral anticoagulation with DOACs in ischaemic stroke associated with atrial fibrillation are justified to confirm the acceptable safety and efficacy of this strategy. Four such randomised controlled trials (collectively planned to include around 9000 participants) are underway, either using single cutoff timepoints for early versus late DOAC-administration initiation, or selecting DOAC-administration timing according to the severity and imaging features of the ischaemic stroke. The results of these trials should help to establish the optimal timing to initiate DOAC administration after recent ischaemic stroke and whether the timing should differ according to stroke severity. Results of these trials are expected from 2021.

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Section: Introductionmentioning

confidence: 99%

Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation

Seiffge

Werring

Paciaroni

et al. 2019

The Lancet Neurology

186

142

View full text Add to dashboard Cite

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“…Oral anticoagulants (OAC) are beneficial in the prevention of ischaemic stroke and systemic embolism in patients with atrial fibrillation. Vitamin K antagonists (VKA) were the only option for OAC therapy for many years, but since 2010, direct thrombin inhibitors [2] (dabigatran) and factor Xa inhibitors [3] (apixaban, edoxaban and rivaroxaban)—termed non-vitamin K antagonist oral anticoagulants (NOAC)—have emerged as an alternative option.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use

et al. 2019

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ObjectiveTo obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.MethodsWe conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel–Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.ResultsWe identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03–7.07, p < 0.0001, I2 = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24–13.07 ml, p < 0.00001; I2 = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74–4.97, p < 0.00001; I2 = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61–2.07, p < 0.00001, I2 = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52–3.31, p < 0.00001, I2 = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.ConclusionThis meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.Electronic supplementary materialThe online version of this article (10.1007/s00415-019-09536-1) contains supplementary material, which is available to authorized users.

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“…Ein aktueller Cochrane-Review bestätigt die Empfehlung der ESC-Leitlinie: Er bescheinigt den NOAK gegenüber VKA ein signifikant besseres Verhältnis in der Reduktion von Schlaganfällen, sonstigen thromboembolischen Ereignissen und Todesfällen gegenüber dem Auftreten von Blutungen, wie sie alle Gerinnungshemmer hervorrufen [43]. Alle NOAK zeigten in den randomisierten klinischen Prüfungenmit graduellen Unterschiedenbei nierengesunden Patienten mit nvVHF sowie bei Patienten mit einer nicht dialysepflichtigen Niereninsuffizienz ein vergleichbares Effektivitäts-und Sicherheitsprofil gegenüber VKA.…”

Section: Diskussionunclassified

Antikoagulation bei Patienten mit nichtvalvulärem Vorhofflimmern (nvVHF) und eingeschränkter Nierenfunktion (NI)

Zeymer

Bonnemeier

Wanner

2019

Dtsch Med Wochenschr

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ZusammenfassungNichtvalvuläres Vorhofflimmern (nvVHF) ist wegen des assoziierten Schlaganfallrisikos eine Hauptindikation der oralen Antikoagulation. Viele dieser Patienten zeigen eine eingeschränkte Nierenfunktion, die das Schlaganfall- und Blutungsrisiko erhöht. Bei Niereninsuffizienz und nvVHF werden Vitamin-K-Antagonisten (VKA) von den Leitlinien aufgrund der heterogenen Studienlage nur zurückhaltend empfohlen – laut Fachinformation sind sie bei manifester Nierenfunktionsstörung kontraindiziert. Neue orale Antikoagulanzien (NOAK) sind bei Patienten mit Niereninsuffizienz ab einer Kreatinin-Clearance (KrCl) von 25 oder 30 ml/min klinisch untersucht und zugelassen, die Faktor-Xa-Inhibitoren können auch bei einer KrCl > 15 ml/min angewendet werden. NOAK zeigen gegenüber VKA ein günstiges Nutzen-Risiko-Profil bei der Reduktion von Schlaganfällen, sonstigen thromboembolischen Ereignissen und Todesfällen einerseits und beim Auftreten von Blutungen andererseits und werden daher von den ESC-Leitlinien empfohlen.

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Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation

Abstract: Trusted evidence. Informed decisions. Better health.

Cited by 38 publications

References 68 publications

Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation

Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation

Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use

Antikoagulation bei Patienten mit nichtvalvulärem Vorhofflimmern (nvVHF) und eingeschränkter Nierenfunktion (NI)

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