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.

Abstract TMP18: Early versus Late Start of Direct Oral Anticoagulants After an Ischemic Stroke Related to Atrial Fibrillation - An Individual Patient Data Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Gian Marco De Marchis ◽  
David J Seiffge ◽  
Sabine Schädelin ◽  
Duncan Wilson ◽  
Valeria Caso ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Data Analysis ◽  
Individual Patient Data ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hemorrhagic Transformation ◽  
Patient Data ◽  
Hazard Ratios ◽  
Late Start

Background: The optimal timepoint of starting DOAC after an acute ischemic stroke (IS) related to atrial fibrillation (AF) remains unclear. We aimed to compare an early (≤ 5 days of IS) versus late (>5 days of IS) DOAC-start. Methods: Individual patient data analysis of 7 European and Japanese prospective observational cohort studies. We included patients with IS or TIA related to non-valvular AF where a DOAC was started within 30 days. We excluded patients with an intracranial bleeding (ICH) after the index event but prior to DOAC-start. We compared the 30-day rates of recurrent IS and ICH between the groups of early versus late DOAC-start with a landmark analysis at day 5. Results: Overall, 2550 patients were included. Median age was 77 years (IQR 70-84). DOAC were started early in 1362 (53%) patients, late in 1188 (47%). In the whole cohort, 37 patients suffered from a recurrent IS (1.5%), 16 patients (43%) of whom before any DOAC was started. 6 patients (0.2%) had an ICH. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent IS after DOAC-start and within 30 days; two patients (0.1%) suffered from ICH after DOAC-start. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent IS before DOAC was started; 4 patients (0.3%) suffered from ICH after DOAC-start. In the comparison of late versus early DOAC-groups, no difference in the hazard ratios was observed for the endpoint of recurrent IS (HR = 1.15, 95%CI 0.48-2.73, p=0.76) and ICH (HR = 4.71, 95%CI 0.51-43.10, p=0.17). Conclusion: Our results do not corroborate the concern that early anticoagulation - at least when performed with DOACs - increases the risk of hemorrhagic transformation of the brain infarct compared to late anticoagulation. Given the seven times higher risk of recurrent IS - with almost half of recurrent IS occurring before any DOAC-start - an early DOAC-start after AF-related IS may be reasonable, if inclusion in the ongoing trials (the recommended option) is not possible.

P1860Unfractionated heparin dose and complication rate in catheter ablation of atrial fibrillation, a comparison between uninterrupted therapy with phenprocoumon and direct oral anticoagulants

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Poci ◽  
D Gjermeni ◽  
V Kuehlkamp
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Events ◽  
Anticoagulation Management ◽  
Significant Difference ◽  
The Mean ◽  
Initial Bolus

Abstract Background Catheter ablation of atrial fibrillation is known for the combining risks of thromboembolism (TE) and major bleedings. This urges a better understanding and optimization of the intraprocedural anticoagulation management. Differences in unfractionated heparin (UFH) requirements and anticoagulation time (ACT) levels between patients on different uninterrupted oral anticoagulation (OAC) agents have been studied. However, the clinical relevance, in terms of periprocedural TE and bleeding events, of UFH administration according to ACT monitoring among patients on different OAC agents, needs to be addressed. Objective To evaluate how the ACT monitoring and differences in intraprocedural UFH requirements among different anticoagulant agents, may translate to clinical outcome, in terms of periprocedural incidence of thromboembolic and bleeding events. Methods We retrospectively studied 1571 cases who underwent catheter ablation for atrial fibrillation between January 2011 and May 2017. Cases were on an uninterrupted oral OAC therapy of Vitamin K Antagonists (VKA)(713), Rivaroxaban (RG)(385), Dabigatran (DG)(260), Apixaban (AG)(192) and Edoxaban (EG)(21). First ACT measurements after the initial bolus of UFH (1ehz748.0610U), mean ACT measurements, total UFH doses/kg (Body Weight)/min (duration of procedure) and incidence of major periprocedural events were compared among the above OAC groups. Results The mean ACT (sec) was significantly lower in the AG and greater in the VKA (313,7±47 vs 340,5±49, p<0,001). Significantly lower UFH doses (U/kg/min) were required to reach the target ACT in VKA compared to RG, DG, AG and EG (0,69±0,4 vs 1,41±0,76; 1,42±0,7; 1,63±0,8; 1,37±0,4 respectively, p<0,001) The proportion of patients who achieved a target ACT value within 30 minutes after the fixed first UFH Bolus of 10 000 U was significantly lower in DG and AG compared to VKA, EG and RG group (51,5% and 49% vs 53%, 71,4%, and 61,8% respectively p=0,005). The incidence of periprocedural TE events and bleedings showed no significant difference among OAC groups. However, the 22 patients with a periprocedural TE event had significantly lower UFH doses (U)/ Duration of catheter ablation (min) compared to the ones without periprocedural TE (62,71±44,5 vs 94,4±66,4, p=0,026), despite equivalent mean ACT values between these two groups. Patients with a periprocedural TE had also a significantly older Age (69,6±10 vs 64±10 p=0,01, higher CHADSVASC Score (3,64±1,76 vs 2,63±1,7 p=0,006), longer duration of procedure (188,9±79,1 vs 144,9±57 p=0,0001) and higher pre-Ablation INR values (2,2±0,6 vs 1,7±0,6 p=0,002). Conclusions The average UFH doses required to reach the target ACT were lower in VKA than in NOAC- groups. The incidence of periprocedural TE events and bleedings was equivalent among OAC groups. Patients with TE showed a lower UFH requirement compared to no-TE group, with both groups having mean ACT ≥300 sec.

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 Reasons for Switching from Warfarin to a Direct Oral Anticoagulant: A Retrospective Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5060-5060
Author(s):  
Siavash Piran ◽  
Marlene Robinson ◽  
Erjona Kruja ◽  
Sam Schulman
Keyword(s):  
Atrial Fibrillation ◽  
Cardiac Surgery ◽  
Drug Interactions ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Retrospective Chart Review ◽  
Mechanical Valve ◽  
Adherence Rate ◽  
Valve Prosthesis ◽  
Significant Difference

Abstract Background: Direct oral anticoagulants (DOACs) are slowly replacing warfarin for the prevention of stroke in atrial fibrillation and treatment and secondary prevention of venous thromboembolism. Patients with poor time in therapeutic range (TTR) are often switched to a DOAC. Poor TTR can be due to drug interactions but if the reason is poor compliance, outcomes could be worse using a DOAC without monitoring. Methods: To understand the compliance patterns we performed a retrospective chart review in patients from the anticoagulation clinic at Hamilton General Hospital that were switched from warfarin to a DOAC from April 2013 to April 2018. Patients who were taking warfarin for ≥ 2 months for any indication, except for mechanical valve prosthesis, and who were switched to a DOAC were included. We excluded patients who had a DOAC-to-DOAC switch, patients who had no reported TTR available, and those who were temporarily on warfarin after cardiac surgery. The documented reasons for a switch from warfarin to a DOAC were compared between patients with TTR ≤ 60% and >60%. Non-adherence to international normalized ratio (INR) monitoring was considered if >20% of tests were not done or delayed for more than 2 days. Results: A total of 643 eligible patients were initially screened and 288 patients were excluded: 179 had no available TTR, 93 were temporarily on warfarin after cardiac surgery, 11 were not actually switched from warfarin to a DOAC, and 5 had a DOAC-to-DOAC switch. The remaining 355 patients were included in the analysis: 223 had a TTR ≤ 60% and 132 patients had a TTR >60%. There were no differences in the median age or gender distribution. The most common indication for anticoagulation was atrial fibrillation in both groups. The median TTR was 43% in the TTR ≤ 60% group and 71% in the TTR >60% group. The median duration on anticoagulation with warfarin was significantly longer for the TTR >60% group compared with the TTR ≤ 60% group (42 months versus 19 months; P <0.001). Apixaban was the most common DOAC of choice for the switch in both groups. The most common documented reasons for a switch in the group with a TTR >60% were: switch by another physician for unknown reason (n=36), bleeding (n=30), and patient preference (n=20). The most common reasons for a switch in those with a TTR ≤ 60% were: unstable INR readings (n=42), drug interactions (n=33), and bleeding (n=30). There was no significant difference in the rate of non-adherence with the scheduled INR monitoring (42% in the group with a TTR >60% versus 49% in those with a TTR ≤ 60%). Conclusion: We found that about half of the patients on chronic anticoagulation with warfarin and switched to a DOAC were non-adherent with the scheduled INR monitoring. This, in combination with low TTR, should alert the physician of possible non-compliance with taking DOACs. Further prospective studies are needed to examine the DOAC adherence rate and clinical outcomes in this specific population. Disclosures Schulman: Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.

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