Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation.
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ABSTRACT: Objective
To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years.Methods
Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.Results
In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1).Interpretation
The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78-88.
SUBMITTER: Polymeris AA
PROVIDER: S-EPMC9300111 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundData on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce.Patients and methodsBased on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome - the composite of recurrent ischemic stroke, major bleeding, and all-cause death - among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders.ResultsWe analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC.Discussion and conclusionThe overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.
| S-EPMC9446322 | biostudies-literature
Project description:ObjectiveWe compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.MethodsWe conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).ResultsWe included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09).InterpretationDOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834.
| S-EPMC6563449 | biostudies-literature
Project description:The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk-benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs. However, both dabigatran 150 twice daily and rivaroxaban have a slightly higher incidence of gastrointestinal bleeding when compared with VKAs. The article will delineate the current knowledge as well as scientific gaps related to the choice and dosage of anticoagulation regimens for various NVAF subsets and will address certain common clinical scenarios requiring special considerations. The article also addresses the shortcomings of NOACs: lack of therapeutic pharmacokinetic and pharmacodynamic targets, absence of tools to assess compliance and efficacy, rigid and limited dosage options, and absence of effective and inexpensive reversal agents.
| S-EPMC6490750 | biostudies-literature
Project description:The aims of this article are to review the evidence regarding the use of non-vitamin K oral anticoagulants (NOACs) for secondary stroke prevention as compared to vitamin K antagonists in patients with atrial fibrillation (AF) and in patients with embolic strokes of uncertain source (ESUS), and when to initiate or resume anticoagulation after an ischaemic stroke or intracranial haemorrhage. Four large trials compared NOACs with warfarin in patients with AF. In our meta-analyses, the rate of all stroke or systemic embolism (SE) was 4.94% with NOACs vs. 5.73% with warfarin. Among the patients with AF and previous transient ischaemic attack or ischaemic stroke, the rate of haemorrhagic stroke was halved with a NOAC vs. warfarin, and the rate of major bleeding was 5.7% with a NOAC vs. 6.4% with warfarin. There was no significant difference in mortality. In a trial comparing apixaban with aspirin in patients with AF, the rate of stroke or SE was 2.4% at 1 year with apixaban vs. 9.2% at 1 year with aspirin and the rates of major bleeding were 4.1% with apixaban vs. 2.9% with aspirin. Data from registries confirmed the results from the randomized trials. Initiation or resumption of anticoagulation after ischaemic stroke or cerebral haemorrhage depends on the size and severity of stroke and the risk of recurrent bleeding. Two large trials tested the hypothesis that NOACs are more effective than 100 mg aspirin in patients with ESUS. Neither trial showed a significant benefit of the NOAC over aspirin. In the meta-analysis, the rate all stroke or SE was 4.94% with NOACs vs. 5.73% with warfarin and the rate of haemorrhagic stroke was halved with a NOAC. The four NOACs had broadly similar efficacy for the major outcomes in secondary stroke prevention.
| S-EPMC7556747 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; e.g., warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (e.g., those with renal impairment) and other specific clinical situations.
| S-EPMC4468938 | biostudies-other
Project description:Atrial fibrillation (AF) is a common heart rhythm disturbance; its incidence increases with age, and it is also an independent risk factor for stroke. Anticoagulation has been proven as the most effective way to reduce the risk of stroke in patients with AF, and vitamin K antagonists have been used for decades as the gold standard treatment. Vitamin K antagonists have a narrow therapeutic window in addition to variable pharmacokinetics and pharmacodynamics, and they frequently interact with food and other drugs, requiring coagulation monitoring to ensure balance between safety and efficacy. The novel oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban selectively target either thrombin or Factor Xa and have predictable pharmacologic profiles, removing the need for routine coagulation monitoring. This article summarizes phase III data in patient subtypes and discusses controversies surrounding AF management with these agents. Results indicate that NOACs in non-valvular AF have an overall improved efficacy-safety profile compared with warfarin. Significantly fewer fatal bleeding events were observed in patients randomized to rivaroxaban, apixaban, or edoxaban compared with those on warfarin, and significant reductions in the incidence of life-threatening bleeding were observed in patients randomized to dabigatran. All four pivotal trials testing the NOACs against warfarin showed significantly lower rates of intracranial bleeding in patients administered NOACs. These results suggest that wider use of NOACs has the potential to improve outcomes for most patients with AF.
| S-EPMC4858545 | biostudies-literature
Project description:Patients with atrial fibrillation (AF) have an increased stroke risk compared with those in sinus rhythm, although the absolute risk for individual patients is modulated by the presence of various additional risk factors. Patient selection for oral anticoagulation for stroke prevention is based on risks of stroke and bleeding. Although CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack) is the most widely used scheme for evaluating stroke risk in patients with AF, several other stroke risk factors are not included; therefore, many patients' stroke risk may be underestimated, contributing to the underuse of anticoagulants. Furthermore, a substantial proportion of patients are categorized as being at moderate risk (CHADS2 = 1), and there has been some ambiguity regarding optimum thromboprophylaxis in this group. The refinement of CHADS2 , CHA2 DS2 -VASc (Congestive heart failure, Hypertension, Age 75 years [2 points], Diabetes mellitus, Stroke or transient ischemic attack [2 points], Vascular disease, Age 65 to 74 years, Sex category [female]), considers additional risk factors. Its main advantage is its ability to identify patients truly at low risk of thromboembolism (CHA2 DS2 -VASc = 0), who are unlikely to benefit from antithrombotic therapy. For all others, an oral anticoagulant may be the preferred approach, simplifying clinical decision making. Implementation of CHA2 DS2 -VASc may also result in an increased proportion of patients receiving anticoagulation. The emergence of newer oral anticoagulants that can be given without routine coagulation monitoring, with improved benefit-risk profiles vs vitamin K antagonists, promises to simplify therapy for patients with AF at risk of stroke. This, coupled with advances in stroke risk stratification, is expected to improve patient outcomes and reduce the burden of AF-related stroke.
| S-EPMC6649625 | biostudies-literature
Project description:IntroductionIt is unknown whether the type of treatment (direct oral anticoagulant versus vitamin K antagonist) and the time of treatment introduction (early versus late) may affect the functional outcome in stroke patients with atrial fibrillation. We aimed to develop and validate a nomogram model including direct oral anticoagulant/vitamin K antagonist and early/late oral anticoagulant introduction for predicting the probability of unfavourable outcome after stroke in atrial fibrillation-patients.Patients and methodsWe conducted an individual patient data analysis of four prospective studies. Unfavourable functional outcome was defined as three-month modified Rankin Scale score 3 -6. To generate the nomogram, five independent predictors including age (<65 years, reference; 65--79; or 80), National Institutes of Health Stroke Scale score (0--5 points, reference; 6--15; 16--25; or >25), acute revascularisation treatments (yes, reference, or no), direct oral anticoagulant (reference) or vitamin K antagonist, and early (7 days, reference) or late (8--30) anticoagulant introduction entered into a final logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve.ResultsA total of 2102 patients with complete data for generating the nomogram was randomly dichotomised into training (n = 1553) and test (n = 549) sets. The area under the receiver operating characteristic curve was 0.822 (95% confidence interval, CI: 0.800--0.844) in the training set and 0.803 (95% CI: 0.764--0.842) in the test set. The model was adequately calibrated (9.852; p = 0.276 for the Hosmer--Lemeshow test).Discussion and conclusionOur nomogram is the first model including type of oral anticoagulant and time of treatment introduction to predict the probability of three-month unfavourable outcome in a large multicentre cohort of stroke patients with atrial fibrillation.
| S-EPMC7856583 | biostudies-literature
Project description:After recent randomized control trials (RCTs), non-vitamin K oral anticoagulants (NAOAs) are now widely being used in patients with atrial fibrillation (AF) worldwide. However, current guidelines for the use of NOACs in patients with AF are derived mostly using a Caucasian population and non-stroke patients. Relatively few Asian patients with AF and stroke are included in the recent RCTs. As a result, the optimal use of NOACs in this particular group of patients is remains to be settled. The optimal dose of NOACs and response to current dose of NOACs of Asian patients with AF and stroke may differ from those of westerners and patients without stroke. We reviewed available research on NOACs by searching PubMed and ClinicalTrials.gov published in English up to December 2015. In this review, the characteristics of Asian AF patients with prior stroke/transient ischemic attack, which might influence the efficacy and safety profiles of NOACs, are discussed. In addition, we summarize the risk factors for bleeding complications on NOACs, which are related or unrelated with the blood level of NOACs. Lastly, we provide recent data of reduced dose of NOACs from RCTs or large cohorts. The results reviewed herein call for clinical trials to test whether a reduced dose of NOACs is beneficial in Asian patients with AF and stroke. In the meantime, further researches are needed to establish the safety and efficacy of dose-adjusted NOACs considering both blood levels of NOACs and fragility of patients in Asian patients with AF and stroke.
| S-EPMC4904388 | biostudies-literature
Project description:Objective To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.Design Systematic review, network meta-analysis, and cost effectiveness analysis. Data sources Medline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studies Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results 23 randomised trials involving 94?656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.Conclusions The network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registration PROSPERO CRD 42013005324.
| S-EPMC5704695 | biostudies-other