Epidemiology of Subtherapeutic Anticoagulation in the United States

Rose, Adam J.; Ozonoff, Al; Grant, Richard W.; Henault, Lori

doi:10.1161/circoutcomes.109.862763

Cited by 56 publications

(42 citation statements)

References 38 publications

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“…Interestingly, although there are significant differences in the recommended guidelines for warfarin, healthcare systems and ethnic groups between the 2 studies, the frequency of under-dosing was similar between that study and ours. There may be common underlying causes for insufficient doses of warfarin, such as non-adherence, interruptions for procedures, recent dose reductions and second or more consecutive low INR values [13] . When warfarin is prescribed for NVAF patients, PT-INR must be maintained within the optimal range as much as possible.…”

Section: Oacs Included Warfarin and Dabigatran (An Noac) Antiplatelementioning

confidence: 99%

Causes of Ischemic Stroke in Patients with Non-Valvular Atrial Fibrillation

et al. 2016

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Background: Oral anticoagulants (OACs) reduce the incidence of embolic events associated with non-valvular atrial fibrillation (NVAF); however, ischemic stroke can still occur in such patients. Although there are various causes of ischemic stroke in patients with NVAF, their medication status at onset has scarcely been studied. This retrospective study aimed to determine the underlying causes of ischemic stroke in patients with NVAF in relation to pre-stroke anticoagulation. Methods: Among Japanese patients with acute ischemic stroke enrolled in the Fukuoka Stroke Registry from June 2007 to May 2013, 1,302 patients with NVAF who had been hospitalized within 24 h of onset were included in this study, and their backgrounds, pre-stroke use of OACs and prothrombin time-international normalized ratio (PT-INR) on admission were investigated. Strokes were regarded as being non-cardioembolic (CE) type when causes other than NVAF had been identified. The sub-therapeutic range (TR) for warfarin was defined according to Japanese guidelines for pharmacotherapy of atrial fibrillation. Results: Atrial fibrillation had been diagnosed prior to onset of stroke in 704 of 1,302 patients (54%). However, it had not been detected before or on admission, but identified later during hospitalization in 270 patients (21%). Of the patients who had atrial fibrillation on admission but had not been diagnosed as having it, 108 (8%) had not received any medication before onset of stroke and 220 (17%) had received medications other than OACs. OACs had been administered to 415 (59%) of the patients with known atrial fibrillation. The proportion of pre-stroke CHADS₂ or CHA₂DS₂-VASc scores ≥1 ranged from 93 to 99% depending on whether atrial fibrillation had been diagnosed or anticoagulation therapy administered before stroke onset. The PT-INR was in the sub-TR on admission in 283 of 399 patients (71%) receiving warfarin. Male sex, smoking and previous stroke were more prevalent in patients with values within or over the TR of PT-INR than in those in the sub-TR. Non-CE stroke was more prevalent in patients with values above the lower therapeutic limit of the recommended PT-INR than in those in the sub-TR (p < 0.001). The number of CE strokes was much smaller in patients with high admission PT-INR values; this was not observed for non-CE ischemic strokes (p < 0.001). Conclusions: In the clinical setting, under-diagnosis, underuse and sub-therapeutic doses of OACs are major causes of ischemic stroke in patients with NVAF. However, non-CE ischemic strokes may develop in patients receiving therapeutic doses of warfarin.

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Section: Oacs Included Warfarin and Dabigatran (An Noac) Antiplatelementioning

confidence: 99%

Causes of Ischemic Stroke in Patients with Non-Valvular Atrial Fibrillation

et al. 2016

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“…Aux États-Unis sur 4489 patients sous AVK, sur deux ans de suivi, 34 % ont eu au moins une fois un INR inférieur à 1,5. Un patient sur cinq avec INR inférieur à 1,5 a fait un événement thromboembolique (95 % IC : 12,2-35,4 %) (Rose et al, 2009).…”

Section: Antiagrégants Plaquettaires : Mono-et Bithérapie Versus Placebounclassified

Prévention secondaire des infarctus cérébraux liés à l’arythmie complète par fibrillation auriculaire : quel(s) traitement(s) et dans quel(s) délai(s) ?

Muresan

Alamowitch

2011

Pratique Neurologique - FMC

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“…2 It is used for the prevention of thromboembolic complications of various disorders including atrial fibrillation, venous thromboembolism, and valvular heart disease. 3 Despite the fact that this is a highly efficacious therapy when titrated to the appropriate therapeutic range, the titration and dosing of warfarin are the most challenging and labor-intensive aspects of this therapy. There are many factors that influence its pharmacokinetics and pharmacodynamics including patient age, concurrent medications, diet, comorbidities, and genetics.…”

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confidence: 99%

“…It has been observed that low INR is addressed without a sense of urgency in the community setting, but this may be related to 2008 American College of Clinical Pharmacy guidelines that reinforce a lack of urgency in addressing low INR values, because they contain limited guidance about how to address low INR despite offering detailed instructions about how to deal with elevated INR. 3 The literature also shows that a significant proportion of patients with unstable INR values are poorly informed about the reasons for and the clinical importance of oral anticoagulation therapy for their health. Most of these patients also had insufficient knowledge of oral anticoagulation mechanism of action, the rules of treatment monitoring, and the risk of thrombotic and bleeding complications, and many of these patients stated this as the reason for poor compliance.…”

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confidence: 99%

Clinical trials for pharmacogenomics testing for warfarin dosing: Relevance to general community practices

Sidiropoulos

2011

Genetics in Medicine

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O ral anticoagulation with warfarin requires a relatively individualized therapeutic approach to establish appropriate dosing. It is of the utmost importance to administer correct initial dosing given warfarin's narrow therapeutic index and devastating complications. Warfarin pharmacogenomic testing is one element of many that may be used to appropriately tailor therapy. Numerous studies have evaluated the clinical benefit of genotyping, and many times the results are equivocal. The majority of these studies have been performed in the specialized anticoagulation clinic setting.In this issue of the journal, Caldwell and coworkers 1 reported on "A randomized, controlled trial of genetic-based Coumadin initiation." The study setting is an anticoagulation clinic and they found, despite improved initial therapeutic dose estimation when genotype was known, outcomes were ultimately impacted by clinical management regardless of genotype knowledge. It is important when interpreting these conclusions, however, to acknowledge that there are two main oral anticoagulation management settings in the United States: specialized anticoagulation clinics and community clinics (usual care, health maintenance organization setting); the services and outcomes of which are not equivalent for numerous reasons. These differences prohibit meaningful generalization of results that universally invalidate the clinical impact of pharmacogenomics testing.Warfarin is the primary drug prescribed for long-term oral anticoagulation therapy in the United States with close to 4 million patients taking this medication. 2 It is used for the prevention of thromboembolic complications of various disorders including atrial fibrillation, venous thromboembolism, and valvular heart disease. 3 Despite the fact that this is a highly efficacious therapy when titrated to the appropriate therapeutic range, the titration and dosing of warfarin are the most challenging and labor-intensive aspects of this therapy. There are many factors that influence its pharmacokinetics and pharmacodynamics including patient age, concurrent medications, diet, comorbidities, and genetics. 4 Patient comprehension/health literacy, education, receptivity to details regarding medical illness, and various patient demographic and psychosocial factors that are associated with adherence to therapy and the associated monitoring also play a significant role in achieving a desirable therapeutic range. [5][6][7] All these factors combined, many of which are in a state of constant flux, result in significant inter-and intraindividual variability. This makes it difficult to accurately determine individual therapeutic dose to maintain a stable and appropriate international normalized ratio (INR). Accuracy in this regard, however, is crucial given warfarin's very narrow therapeutic index and the strong association between the time spent in the therapeutic range with risk of morbidity and mortality due to bleeding and thromboembolism. 8 -12 Ultimately, correct initial dosing and appropriate moni...

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Epidemiology of Subtherapeutic Anticoagulation in the United States

Abstract: Background-Low international normalized ratio (INR;Յ1.

Cited by 56 publications

References 38 publications

Causes of Ischemic Stroke in Patients with Non-Valvular Atrial Fibrillation

Causes of Ischemic Stroke in Patients with Non-Valvular Atrial Fibrillation

Prévention secondaire des infarctus cérébraux liés à l’arythmie complète par fibrillation auriculaire : quel(s) traitement(s) et dans quel(s) délai(s) ?

Clinical trials for pharmacogenomics testing for warfarin dosing: Relevance to general community practices

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