Dataset Information

Association of preceding antithrombotic therapy in atrial fibrillation patients with ischaemic stroke, intracranial haemorrhage, or gastrointestinal bleed and mortality.

ABSTRACT:

Aims

To analyse 90-day mortality in atrial fibrillation (AF) patients after a stroke or a severe bleed and assess associations with the type of antithrombotic treatment at the event.

Methods and results

From the Stockholm Healthcare database, we selected 6017 patients with a known history of AF who were diagnosed with ischaemic stroke, 3006 with intracranial haemorrhage, and 4291 with a severe gastrointestinal bleed (GIB). The 90-day mortality rates were 25.1% after ischaemic stroke, 31.6% after intracranial haemorrhage, and 16.2% after severe GIB. We used Cox regression and propensity score-matched analyses to test the association between antithrombotic treatment at the event and 90-day mortality. After intracranial haemorrhage, there was a significantly higher mortality rate in warfarin compared to non-vitamin K oral anticoagulant (NOAC)-treated patients [adjusted hazard ratio (aHR) 1.36, 95% confidence interval (CI) 1.04-1.78]. After an ischaemic stroke and a severe GIB, patients receiving antiplatelets or no antithrombotic treatment had significantly higher mortality rates compared to patients on NOACs, but there was no difference comparing warfarin to NOACs (aHR 0.84, CI 0.63-1.12 after ischaemic stroke, aHR 0.91, CI 0.66-1.25 after severe GIB). Propensity score-matched analysis yielded similar results.

Conclusion

Mortality rates were high in AF patients suffering from an ischaemic stroke, an intracranial haemorrhage, or a severe GIB. NOAC treatment was associated with a lower 90-day mortality after intracranial haemorrhage than warfarin.

SUBMITTER: Komen JJ

PROVIDER: S-EPMC7811399 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Association of preceding antithrombotic therapy in atrial fibrillation patients with ischaemic stroke, intracranial haemorrhage, or gastrointestinal bleed and mortality.

Komen Joris J JJ Forslund Tomas T Mantel-Teeuwisse Aukje K AK Klungel Olaf H OH von Euler Mia M Braunschweig Frieder F Wallén Håkan H Hjemdahl Paul P

European heart journal. Cardiovascular pharmacotherapy 20210101 1

<h4>Aims</h4>To analyse 90-day mortality in atrial fibrillation (AF) patients after a stroke or a severe bleed and assess associations with the type of antithrombotic treatment at the event.<h4>Methods and results</h4>From the Stockholm Healthcare database, we selected 6017 patients with a known history of AF who were diagnosed with ischaemic stroke, 3006 with intracranial haemorrhage, and 4291 with a severe gastrointestinal bleed (GIB). The 90-day mortality rates were 25.1% after ischaemic stro ...[more]

PMID: 31665368

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Project description:Study questionWhat are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation?MethodsThis Danish cohort study (1996-2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models.Study answer and limitations4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with non-resumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment.What this study addsAmong patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding.Funding, competing interests, data sharingThis study was supported by a grant from Boehringer-Ingelheim. Competing interests are available in the full paper on bmj.com. The authors have no additional data to share.

Project description:BackgroundCerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack.MethodsOur observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316.FindingsBetween Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0-20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1-5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27-10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29-0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53-0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60-0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07-0·43, p=0·0065; and 0·33, 0·14-0·51, p=0·00059, respectively).InterpretationIn patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation.FundingThe Stroke Association and the British Heart Foundation.

Project description:ObjectiveWe report on: (1) the proportion of patients with known atrial fibrillation (AF); and (2) demographic, clinical or radiological differences between patients with known AF (and not treated) and patients with newly diagnosed AF, in a cohort of patients who presented with ischaemic stroke or transient ischaemic attack (TIA) not previously treated with anticoagulation.DesignWe reviewed cross-sectional baseline demographic and clinical data from a prospective observational cohort study, (CROMIS-2).SettingPatients were recruited from 79 hospital stroke centres throughout the UK and one centre in the Netherlands.ParticipantsPatients were eligible if they were adults who presented with ischaemic stroke or TIA and AF and had not been previously treated with oral anticoagulation.Main outcome measuresProportion of patients with known AF before index ischaemic stroke or TIA from a cohort of patients who have not been previously treated with oral anticoagulation. Secondary analysis includes the comparison of CHA2DS2-VASc and HAS-BLED scores and other demographics and risk factors between those with newly diagnosed AF and those with previously known AF.ResultsOf 1470 patients included in the analysis (mean age 76 years (SD 10)), 622 (42%) were female; 999 (68%) patients had newly diagnosed AF and 471 (32%) patients had known AF. Of the 471 patients with known AF, 68% had a strong indication for anticoagulation and 89% should have been considered for anticoagulation based upon CHA2DS2-VASc score. Patients with known AF were more likely to have a prior history of dementia (4% vs 2%, p=0.02) and had higher HAS-BLED scores (median 3 vs 2). CHA2DS2-VASc, other risk factors and demographics were similar.ConclusionsAbout 1/3 of patients who present with stroke and have AF who have not been treated with oral anticoagulation have previously known AF. Of these patients, at least 68% were not adequately treated with oral anticoagulation.Trial registration numberNCT02513316.

Project description:BackgroundAbout 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 developmentsProspective 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.

Dataset Information

Association of preceding antithrombotic therapy in atrial fibrillation patients with ischaemic stroke, intracranial haemorrhage, or gastrointestinal bleed and mortality.

Aims

Methods and results

Conclusion

Publications

Association of preceding antithrombotic therapy in atrial fibrillation patients with ischaemic stroke, intracranial haemorrhage, or gastrointestinal bleed and mortality.

Similar Datasets

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