Potentially Preventable Strokes in High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Anticoagulated

Gladstone, David J.; Bui, Esther; Fang, Jiming; Laupacis, Andreas; Lindsay, M. Patrice; Tu, Jack V.; Silver, Frank L.; Kapral, Moira K.

doi:10.1161/strokeaha.108.516344

Cited by 361 publications

(267 citation statements)

References 45 publications

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“…cause of concerns about bleeding, physicians tend to underdose warfarin, reducing its therapeutic efficacy. 25 Many reports document some relationship between warfarin dose and warfarin sensitivity genotype. Furthermore, there is considerable consensus in the findings among research groups from different regions ( Tables 1-5).…”

Section: Discussionmentioning

confidence: 99%

“…Gladstone et al 25 noted that atrial fibrillation-related strokes are severe, with a 1-year mortality rate of 50%, and that warfarin anticoagulation reduces the relative risk of ischemic stroke by 65% and the risk of death by 25%. This group reported that, among patients in the Registry of the Canadian Stroke Network, only 40% had been prescribed warfarin; 30%, combined antiplatelet therapy; and 29%, no antithrombotic drug.…”

Section: Incidence Of Warfarin-related Adesmentioning

confidence: 99%

See 1 more Smart Citation

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Moyer

O’Kane

Baudhuin

et al. 2009

Mayo Clinic Proceedings

114

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ADE = adverse drug event; AEI = American Enterprise Institute; ASPE = allele-specific primer extension; CYP2C9 = cytochrome P450 2C9; INR = international normalized ratio; PCR = polymerase chain reaction; SNP = single-nucleotide polymorphism; VitKH 2 = vitamin K hydroquinone; VKOR = vitamin K epoxide reductase; VKORC1 = VKOR complex, subunit 1 W arfarin is a well-accepted therapy used for the prevention of stroke in patients with atrial fibrillation, for prophylaxis of venous thromboembolism and pulmonary embolism in patients with prosthetic heart valves and myocardial infarction, and for prevention of pulmonary embolism or deep venous thrombosis in patients undergoing orthopedic surgery or with a history of venous or arterial thromboembolism. Many reviews and clinical practice guidelines (summarized by Ansell et al, 1 Baglin et al, 2 Flockhart et al, 3 Husted et al, 4 and Singer et al 5 ) outline the substantial benefits of warfarin therapy for the prevention of strokes in these patients. The American Enterprise Institute (AEI)-Brookings Joint Center for Regulatory Studies Report, which reviewed the use of warfarin in the United States, estimates that approximately 2 million US citizens are prescribed warfarin annually. 6 In 2003, a total of 21.2 million prescriptions were written for oral warfarin in the United States. 7 Warfarin interferes with coagulation by inhibiting regeneration of the reduced form of vitamin K, a cofactor in the γ-glutamyl-carboxylase -mediated activation of coagulation factors II, VII, IX, and X ( Figure 1). The oxidized, inactive form of vitamin K is converted to the reduced form of vitamin K by vitamin K epoxide reductase (VKOR); warfarin inhibits VKOR, resulting in less of the reduced form of vitamin K available to support the factor carboxylation required to sustain the coagulation cascade. 8 Warfarin has a narrow therapeutic index that contributes either to therapeutic failure (potentially leading to stroke or other complications) or therapeutic excess (potentially leading to bleeding and hemorrhage). Many surveys have described the incidence of warfarin-related adverse drugThe antithrombotic benefits of warfarin are countered by a narrow therapeutic index that contributes to excessive bleeding or cerebrovascular clotting and stroke in some patients. This article reviews the current literature describing warfarin sensitivity genotyping and compares the results of that review to the findings of our study in 189 patients at Mayo Clinic conducted between June 2001 and April 2003. For the review of the literature, we identified relevant peer-reviewed articles by searching the Web of Knowledge using key word warfarin-related adverse event. For the 189 Mayo Clinic patients initiating warfarin therapy to achieve a target international normalized ratio (INR) in the range of 2.0 to 3.5, we analyzed the CYP2C9 (cytochrome P450 2C9) and VKORC1 (vitamin K epoxide reductase complex, subunit 1) genetic loci to study the relationship among the initial warfarin dose, steady-state dose, time to ach...

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Section: Discussionmentioning

confidence: 99%

Section: Incidence Of Warfarin-related Adesmentioning

confidence: 99%

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Moyer

O’Kane

Baudhuin

et al. 2009

Mayo Clinic Proceedings

114

View full text Add to dashboard Cite

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“…AF accounts for 15% of all ischemic strokes and one third of all strokes in the elderly 4. These strokes result in permanent disability in 60% of patients and death in up to 20% 5. Anticoagulation (AC) therapy is the cornerstone for stroke prevention in patients with AF.…”

Section: Introductionmentioning

confidence: 99%

SUPPORT‐AF: Piloting a Multi‐Faceted, Electronic Medical Record‐Based Intervention to Improve Prescription of Anticoagulation

Kapoor

Amroze

Golden

et al. 2018

JAHA

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BackgroundOnly 50% of eligible atrial fibrillation (AF) patients receive anticoagulation (AC). Feasibility and effectiveness of electronic medical record (EMR)–based interventions to profile and raise provider AC percentage is poorly understood. The SUPPORT‐AF (Supporting Use of AC Through Provider Profiling of Oral AC Therapy for AF) study aims to improve rates of adherence to AC guidelines by developing and delivering supportive tools based on the EMR to providers treating patients with AF.Methods and ResultsWe emailed cardiologists and community‐based primary care providers affiliated with our institution reports of their AC percentage relative to peers. We also sent an electronic medical record–based message to these providers the day before an appointment with an atrial fibrillation patient who was eligible but not receiving AC. The electronic medical record message asked the provider to discuss AC with the patient if he or she deemed it appropriate. To assess feasibility, we tracked provider review of our correspondence. We also tracked the change in AC for intervention providers relative to alternate primary care providers not receiving our intervention. We identified 3786, 1054, and 566 patients cared for by 49 cardiology providers, 90 community‐based primary care providers, and 88 control providers, respectively. At baseline, the percentage of AC was 71.3%, 63.5%, and 58.3% for these 3 respective groups. Intervention providers reviewed our e‐mails and electronic medical record messages 45% and 96% of the time, respectively. For providers responding, patient refusal was the most common reason for patients not being on AC (21%) followed by high bleeding risk (19%). At follow‐up 10 weeks later, change in AC was no different for either cardiology or community‐based primary care providers relative to controls (0.2% lower and 0.01% higher, respectively).ConclusionsOur intervention profiling AC was feasible, but not sufficient to increase AC in our population.

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“…3 Stroke registry data in Ontario showed that for up to 75% of high-risk patients with atrial fibrillation who were admitted to hospital with a stroke and who were taking warfarin at the time of admission, the international normalized ratio (INR) was subtherapeutic. 4 Direct-acting oral anticoagulants such as apixaban, which are much simpler to dose, do not require INR monitoring, and are associated with fewer drug and food interactions, have therefore become more attractive options for many clinicians and patients.…”

Section: Introductionmentioning

confidence: 99%

Appropriateness of Apixaban Dosing to Prevent Stroke in Patients with Atrial Fibrillation: A Pilot Study

Carlin

Pickering

Schulman³

2016

CJHP

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Background:The ARISTOTLE study investigated apixaban, at a dose of 5 mg PO bid, for the prevention of stroke in patients with atrial fibrillation; however, it has been noted anecdotally that many patients are receiving 2.5 mg PO bid, despite being eligible for the full dosage. A recent study examining the use of dabigatran and rivaroxaban found that many patients were receiving these medications inappropriately; however, a literature search conducted in April 2016 showed that apixaban had not been formally studied in this context.

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Potentially Preventable Strokes in High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Anticoagulated

Cited by 361 publications

References 45 publications

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

SUPPORT‐AF: Piloting a Multi‐Faceted, Electronic Medical Record‐Based Intervention to Improve Prescription of Anticoagulation

Appropriateness of Apixaban Dosing to Prevent Stroke in Patients with Atrial Fibrillation: A Pilot Study

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