Joint Latent Class Analysis of Oral Anticoagulation Use and Risk of Stroke or Systemic Thromboembolism in Patients with Atrial Fibrillation.
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ABSTRACT: Background
Oral anticoagulation (OAC) is recommended to reduce the risk of stroke or systemic thromboembolism (TE) in atrial fibrillation (AF). In this study, we applied novel joint latent class mixed models to identify heterogeneous patterns of trajectories of OAC use and determined how these trajectories are associated with risks of thromboembolic outcomes.Methods and results
We used 2013-2016 claims data from a 5% random sample of Medicare beneficiaries, obtained from the Centers for Medicare and Medicaid Services. Our study sample included 16,399 patients newly diagnosed with AF in 2014-2015 who were followed for 12 months after the first AF diagnosis and filled at least one OAC prescription in this time period. OAC use was defined as the number of days covered with OACs every 30-day interval after the first AF diagnosis. We used a joint latent class mixed model to simultaneously evaluate the longitudinal patterns of OAC use and time to stroke or TE, while adjusting for age, race, CHAD2S2-VASc score and HAS-BLED score. Five classes of OAC use patterns were identified: late users (17.8%); late initiators (12.5%); early discontinuers (18.6%); late discontinuers (15.4%); and continuous users (35.6%). Compared with continuous users, the risk of stroke or TE was higher for participants in the late initiators (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.49-2.01) and late discontinuers (HR 1.23, 95% CI 1.04-1.45) classes.Conclusion
Late initiators and late discontinuers had a higher risk of stroke or TE than continuous users. Early initiation and continuous OAC use is important in preventing stroke and TE among patients diagnosed with AF.
SUBMITTER: Chen N
PROVIDER: S-EPMC8440356 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Patients with atrial fibrillation (AF) experiencing ischemic stroke despite oral anticoagulation (OAC), i.e., breakthrough strokes, are not uncommon, and represent an important clinical subgroup in view of the consistently high risk of stroke recurrence and mortality. The understanding of the heterogenous potential mechanism underlying OAC failure is essential in order to implement specific therapeutic measures aimed at reducing the risk of recurrent ischemic stroke. However, due to the incomplete comprehension of this phenomenon and the limited available data, secondary stroke prevention in such high-risk patients represents a clinical dilemma. There are several available strategies to prevent ischemic stroke recurrence in AF patients with breakthrough stroke in the absence of competing causes unrelated to AF, and these include continuation or change in the type of OAC, addition of antiplatelet therapy, left atrial appendage closure, or any combination of the above options. However, due to the limited available data, the latest guidelines do not provide any specific recommendations about which of the above strategies may be preferred. This review describes the incidence, the clinical impact and the potential mechanisms underlying OAC failure in AF patients. Furthermore, the evidence supporting each of the above therapeutic options for secondary stroke prevention and the potential future directions will be discussed.
| S-EPMC10532406 | biostudies-literature
Project description:ObjectiveOral anticoagulation (OAC) prescribed to AF patients for the prevention of cardioembolic complications likely has the added benefit of preventing venous thromboembolism (VTE). This study evaluated, among AF patients who are anticoagulated, whether type of OAC was associated with subsequent VTE risk.MethodsNon-valvular AF patients prescribed OACs between 2010 and September 2015 were identified via the MarketScan administrative claims databases. OACs included warfarin and direct OACs (DOACs: dabigatran, rivaroxaban, and apixaban). Incident VTE was defined by ICD-9-CM codes. Patients were matched on age, sex, CHA2DS2-VASc, and high-dimensional propensity scores. The final analysis included 117,912 AF patients.ResultsIn total, 1357 VTE events accrued over a mean follow-up of 484 days. In multivariable-adjusted, propensity score-matched Cox models, relative to new users of warfarin, risk of incident VTE was lower among new users of dabigatran [hazard ratio (95% confidence interval) = 0.55 (0.47-0.66)] and apixaban [0.51 (0.39-0.68)], but similar among new users of rivaroxaban [1.01 (0.87-1.19)]. In head-to-head DOAC comparisons, VTE risk was lower among users of dabigatran [0.48 (0.36-0.64)] and apixaban [0.61 (0.47-0.78)] vs rivaroxaban. Findings were mostly similar across patient sub-groups.ConclusionsIn this large practice-based population of AF patients prescribed OACs for primary prevention of stroke and systemic embolization, subsequent risk of VTE was lowest among those prescribed apixaban and dabigatran, while risk was similar with prescriptions for warfarin and rivaroxaban. Among AF patients prescribed OACs, lowering the risk of VTE may be an additional benefit of apixaban and dabigatran, beyond the reduced bleeding risk observed in randomized clinical trials.
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Project description:BackgroundNon-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved.AimsWe sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF).MethodsWe recruited hospitalised patients (2013-2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA2DS2-VASc and SAMe-TT2R2 scores with poor adherence.ResultsAmong 396 patients (median age 75.0 years, interquartile range [IQR] 70-80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12-33]; median ARMS score 17 [IQR 17-19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA2DS2-VASc and SAMe-TT2R2 scores were not associated with poor adherence.ConclusionsAdherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients.KEY MESSAGESAdherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke.Independent patient-related factors rather than composite scores were associated with poor adherence.The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.
| S-EPMC8439221 | biostudies-literature
Project description:BackgroundOral anticoagulation (OAC) reduces the risk of thromboembolic events in patients with atrial fibrillation (AF); however, thromboembolism (TE) still can occur despite OAC. Factors associated with residual risk for stroke, systemic embolism, or transient ischemic attack events despite OAC have not been well described.ObjectiveThe purpose of this study was to evaluate the residual risk of thromboembolic events in patients with AF despite OAC.MethodsA total of 18,955 patients were analyzed in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF I and II) using multivariable Cox proportional hazard modeling. Mean age was 72 ± 10.7, and 42% were women. There were 451 outcome events.ResultsThe risk of TE despite OAC increased with CHA2DS2-VASc score: 0.76 (95% confidence interval [CI] 0.63-0.92) events per 100 patient-years for CHA2DS2-VASc score <4 vs 2.01 (95% CI 1.81-2.24) events per 100-patient years for CHA2DS2-VASc score >4. Factors associated with increased risk were previous stroke or transient ischemic attack (hazard ratio [HR] 2.87; 95% CI 2.30-3.59; P <.001), female sex (HR 1.52; 95% CI 1.24-1.86; P <.001), hypertension (HR 1.50; 95% CI 1.09-2.06; P = .01), and permanent AF (HR 1.47; 95% CI 1.12-1.94; P = .001). When transient ischemic attack was excluded, the results were similar, but permanent AF was no longer significantly associated with thromboembolic events.ConclusionPatients with AF have a residual risk of TE with increasing CHA2DS2-VASc score despite OAC. Key risk markers include previous stroke/transient ischemic attack, female sex, hypertension, and permanent AF.
| S-EPMC9795305 | biostudies-literature
Project description:Background and purposeOral anticoagulants (OACs) prevent stroke recurrence and vascular embolism in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Based on empirical consensus, current guidance recommends a "1-3-6-12 days" rule to resume OACs after AIS. This study investigated the suitability of guideline-recommended timing for OAC initiation.MethodsUsing data of 12,307 AF patients hospitalized for AIS, for the period 2012 to 2016, in Taiwan's National Health Insurance Research Database, we constructed a sequence of cohorts of OAC users and propensity score-matched nonusers, creating one cohort on each day of OAC initiation for 30 days since admission. Composite outcome included effectiveness (cardiovascular death, ischemic stroke, myocardial infarction, transient ischemic attack, systemic embolism, and venous thromboembolism) and safety (intracranial hemorrhage, gastrointestinal bleeding, and hematuria) outcomes. Comparing with nonusers, we examined the risks in the early OAC use (within 1-3-6-12 days) or guideline-recommended delayed use. Indirect comparison between the early and delayed use was conducted using mixed treatment comparison.ResultsAcross the AIS severity, the risks of composite or effectiveness outcome were lower in OAC users than nonusers, and the risks were similar between the early and delayed use groups. In patients with severe AIS, early OAC use was associated with an increased risk of safety outcome, with a hazard ratio (HR) of 1.67 (confidence interval [CI]: 1·30-2·13) compared with nonusers and a HR of 1.44 (CI: 0·99-2·09) compared with the delayed use.ConclusionOur study findings support an early OAC initiation in AF patients with mild-to-moderate AIS and a routine delayed use of OACs can be considered in those with severe AIS to avoid a serious bleeding event.
| S-EPMC9251709 | biostudies-literature
Project description:AimsThe prognosis of patients with atrial fibrillation (AF) and ischemic stroke while taking oral anticoagulation is poorly understood. This study aimed to characterize the outcomes of patients following a stroke event while on oral anticoagulation.Methods and resultsIndividual participant data from five pivotal randomized trials of antithrombotic therapy in AF were used to assess the outcomes of patients with a post-randomization ischemic stroke while on study medication (warfarin, standard-, or lower-dose direct oral anticoagulant regimen) during trial follow-up. The primary outcome was recurrent ischemic stroke after the first post-randomization ischemic stroke. The primary analysis included 1163 patients with a first post-randomization ischemic stroke while on study medication (median age 73 years, 39.3% female, 35.4% history of stroke before trial enrollment). During a median continued follow-up of 337 days, 74 patients had a recurrent ischemic stroke [cumulative incidence at 1 year: 7.0%, 95% confidence interval (CI) 5.2%-8.7%]. The cumulative incidence of mortality at 3 months after stroke was 12.4% (95% CI 10.5%-14.4%). Consistent results for the incidence of recurrent ischemic stroke at 1 year were obtained in an analysis accounting for the competing risk of death (6.2%, 95% CI 4.8%-7.9%) and in a landmark analysis excluding the first 2 weeks after the index stroke and only including patients without permanent study drug discontinuation since then (6.8%, 95% CI 4.6%-8.9%).ConclusionPatients with AF and ischemic stroke while on oral anticoagulation are at increased risk of recurrent ischemic stroke and death. These patients currently have an unmet medical need.
| S-EPMC10411934 | biostudies-literature
Project description:ObjectivePrevention 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.MethodsCRYSTAL-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.ResultsCompared 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).ConclusionsAnticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.
| S-EPMC8015049 | biostudies-literature
Project description:Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for stroke and systemic thromboembolism are currently available. The score, with its known limitations, remains as the recommended risk stratification tool in most major guidelines. Once at-risk patients are identified, vitamin K antagonists (VKAs) and, more recently, direct oral anticoagulants (DOACs) are the primary medical therapy for stroke prevention. In those with contraindication for long-term anticoagulation, left atrial appendage occluding devices are developing as a possible alternative therapy. Some controversy exists regarding anticoagulation management for cardioversion of acute AF (<48 hours); however, systemic anticoagulation precardioversion and postcardioversion is recommended for those with longer duration of AF. Anticoagulation management peri-AF ablation is also evolving. Uninterrupted VKA and DOAC therapy has been shown to reduce perioperative thromboembolic risk with no significant escalation in major bleeding. Currently, under investigation is a minimally interrupted approach to anticoagulation with DOACs periablation. Questions remain, especially regarding the delivery of anticoagulation care and integration of wearable rhythm monitors in AF management.
| S-EPMC7881355 | biostudies-literature
Project description:AimsTo investigate if patients with atrial fibrillation (AF) without clear indication for oral anticoagulant (OAC) due to perceived low stroke risk may benefit from OAC treatment when also dementia and intracerebral bleeding risks are considered.Methods and resultsRetrospective study of cross-matched national registries of all individuals in Sweden with a hospital diagnosis of AF between 2006 and 2014 (n = 456 960). Exclusion was made of patients with a baseline CHA2DS2-VASc score >1, not counting female sex, and of patients with previous diagnosis of dementia or intracranial bleeding. After exclusions, 91 254 patients remained in the study of whom 43% used OAC at baseline. Propensity score matching and falsification endpoints were used. Treatment with OAC was associated with lower risk of dementia after adjustment for death as a competing risk [subhazard ratio (sHR) 0.62 with 95% confidence interval (CI) 0.48-0.81]. Regarding the composite brain protection endpoint, OAC treatment was associated with an overall 12% lower risk (sHR 0.88, CI 0.72-1.00). This apparent benefit was restricted to patients aged >65 years, whereas OAC treatment of patients <60 years of age without risk factors appeared to do more harm than good.ConclusionLow-risk AF patients who take OAC have lower risk of dementia than those who do not use OAC. Patients age >65 years appear to benefit from OAC treatment irrespective of stroke risk score.
| S-EPMC6642728 | biostudies-literature
Project description:BackgroundGuidelines recommend that patients with atrial fibrillation (AF) are involved in oral anticoagulant (OAC) treatment decisions. Understanding which OAC attributes AF patients value most could help optimize treatment.ObjectiveTo assess the relationship between patient's stroke knowledge and their preferences for specific OAC attributes.MethodsA cross-sectional online survey was conducted in patients with nonvalvular AF taking an OAC for stroke prevention in the United States, Canada, Germany, France, and Japan. Patients were asked about their stroke knowledge, perception of the seriousness of AF and concern about stroke, and to rank 7 OAC attributes in order of importance. A conjoint analysis was performed to determine the inherent value of 4 attributes.ResultsIn total, 937 patients (mean age [standard deviation] 54.3 [16.6] years; 37.1% female) participated. Of these, 19.5%, 27.9%, and 29.8% had good, moderate, and low stroke knowledge, respectively; 22.8% had no stroke knowledge. Overall, 39.4% of patients (47.5% with good stroke knowledge) perceived AF as very/extremely serious. The OAC attribute ranked as most important was stroke prevention followed by major bleeding risk, other side effects, dosing frequency, antidote availability, dietary restrictions, and use with/without food. In the conjoint analysis, stroke risk reduction was the most valued property, followed by reduction in major bleeding risk, less frequent administration, and administration with/without food. Preferences did not differ with level of stroke knowledge, perception of seriousness of AF, concern of stroke, or medication burden.ConclusionsMost AF patients consider efficacy and safety to be the most important OAC attributes, whereas dosing frequency was deemed as less important.
| S-EPMC6489774 | biostudies-literature