Use of resources and cost implications of stroke prophylaxis with warfarin for patients with nonvalvular atrial fibrillation

doi:10.1016/S1543-5946(03)90001-8

The American Journal of Geriatric Pharmacotherapy

Volume 1, Issue 2, December 2003, Pages 53-60

https://doi.org/10.1016/S1543-5946(03)90001-8 Get rights and content

Abstract

Background: Patients with nonvalvular atrial fibrillation (NVAF) have often been excluded from long-term anticoagulant trials, and therefore patients in clinical practice may have different risk, compliance, and safety considerations from those usually included in such trials.

Objective: The aim of this study was to investigate the use of resources and cost implications of stroke prophylaxis with warfarin in NVAF patients in clinical practice.

Methods: New patients with NVAF referred to an anticoagulation clinic in the United Kingdom were interviewed in person at their first visit and then by telephone every 4 to 6 weeks by an investigator. They were asked about bleeding events and extra physician visits, procedures, or hospital admissions related to bleeding. They were also asked about the method and the cost of transportation to the anticoagulation clinic and the costs involved in days of work missed by the patient and caregiver. Costs of warfarin treatment consisted of the following: (1) cost of the drug, (2) cost of monitoring lie, international normalized ratio, traveling, nurse visits, work missed. postage), and (3) costs associated with complications (ie, bleeding-related physician visits, hospital admissions, related procedures). admissions, related procedures).

Results: A total of 402 patients were included. Mean (SD) age was 72.3 (10.3) years, and 224 patients (55.7%) were men. Mean (SD) follow-up was 19 (8.1) months (range, 1–31 months). Annual event rates were 1.7% (95% CI, 0.4–3.0) for major bleeding and 16.6% (95% CI, 13.0–20.2) for minor bleeding. The mean cost of warfarin treatment per patient per month was £11.0 (95% CI, 10.2–11.6) in patients with no bleeding and £11.9 (95% CI, 10.3–12.5) in patients with minor bleeding (P = NS). The cost was significantly higher in patients with major bleeding (£299.0; 95% CI, 74.6–538.9; P < 0.001). The total cost of warfarin treatment per patient per year was £159.4, and the cost to prevent 1 stroke per year was £5260.20.

Conclusion: In clinical practice in the United Kingdom, anticoagulation with warfarin for prevention of ischemic stroke appeared to be cost-saving relative to the costs of stroke.

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However, the incidence of TIA in young patients with low-risk AF is very low. Thus, identification of risk factors for TIA in young patients with low-risk AF is necessary to more effectively prevent stroke events, because they may have longer survival and require high costs and more medical resources (Abdelhafiz and Wheeldon, 2003). In the current clinical practice, the risk of IS onset is mainly measured using two risk scoring systems: the congestive heart failure (HF), hypertension (HTN), age (≥75 years), diabetes mellitus (DM), and prior stroke, TIA, or thromboembolism history (CHADS2) score (Rietbrock et al., 2008) and the CHA2DS2-VASc score (Pieri et al., 2011), which is a modification of the CHADS2 score aimed at improving stroke risk prediction in patients with AF by adding three risk factors: age (65–74 years), female sex, and history of vascular disease.
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The impact on health‐care costs and utilization of a single out‐of‐range (OOR) INR value not associated with bleeding or thromboembolic complication among chronic warfarin‐treated patients is not well described.
At four large phone‐based anticoagulation clinics (total 14 948 patients), warfarin‐treated patients with atrial fibrillation (AF) or venous thromboembolism were retrospectively propensity matched into an OOR INR group (n = 116) and a control group (n = 58). Types and frequency of contacts (eg, phone, voicemail, facsimile) and personnel involved were identified. A prospective time study analysis of 59 OOR and 92 control patients was performed over 8.5 days to record the time required to care for these patients. 2016 USD cost estimates were generated from average salaries.
OOR and in‐range INR patients experienced an average of 4.2 and 3.2 (P<.001) INR lab draws until two sequential tests were in range. OOR INR patients required an average of 5.3 interactions with the anticoagulation clinic vs 3.7 for in‐range INR patients (P<.001). OOR INR patients more often required phone calls, fewer mailed letters, and more often required multiple types of contact than in‐range INR patients. In the prospective analysis, total median time involved for each OOR INR value was 5.1 minutes (IQR 3.7‐9.5) vs 2.9 minutes (IQR 1.8‐5.8) for control INR values (P<.001). At the clinic level, OOR INR values were associated with a yearly staff cost of $17 938 (IQR $8969‐$31 391).
We quantified the amount of extra anticoagulation staff effort required to manage warfarin‐treated patients who experience a single OOR INR value without bleeding or thromboembolic complications, which leads to higher healthcare utilization costs.
Old and new oral anticoagulants: Food, herbal medicines and drug interactions
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In addition, they can also diminish gut absorption of Vitamin K by altering the gut flora. Although this is rarely of clinical significance (other than in malnourished patient populations), this altered ability to absorb vitamin K can result in lowered synthesis of vitamin K-dependent coagulation proteins and, ultimately, in an increased risk of hemorrhage [35]. Several over-the-counter medications significantly alter warfarin metabolism.
The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs. Direct oral anticoagulants (DOACs) including Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and thrombin inhibitor (dabigatran) are poised to replace warfarin. Phase-3 studies and real-world evaluations have established that the safety profile of DOACs is superior to those of VKAs. However, some pharmacokinetic and pharmacodynamic interactions are expected. Herein we present a critical review of VKAs and DOACs with focus on their potential for interactions with drugs, foods, herbs and over-the-counter medications.
Risk of Hemorrhage and Treatment Costs Associated With Warfarin Drug Interactions in Patients With Atrial Fibrillation
2012, Clinical Therapeutics
Citation Excerpt :
The economic burden of hemorrhages because of the use of warfarin-potentiating drugs is considerable in the United States. In particular, warfarin-related major hemorrhagic events are responsible for a significant portion of the total AF-related treatment costs, with studies reporting mean costs as high as $10,000 to $15,000 per event, depending on the nature and severity of the hemorrhage.12–14 A specialized management approach has been shown to be cost-effective, because of a reduction in both the incidence of stroke and the frequency of adverse events.15
Drug interactions with warfarin are common and may be responsible for increased patient morbidity and treatment costs.
To assess the usage patterns of drugs that potentiate warfarin's anticoagulant activity and discuss their associated relationship with both risk of hemorrhage and treatment costs among warfarin users with atrial fibrillation (AF).
A nested case–control study of long-term warfarin-treated AF patients was conducted using a health insurance claims database. Patients with a hemorrhagic event (cases) were matched to control patients using the incidence density sampling method. Drug-potentiating warfarin effects were identified within 30 days before the hemorrhagic event. Conditional logistic regression was used to calculate the association between use of potentiating drugs and hemorrhage risk. Mean treatment costs and CIs were calculated using the bootstrap method and tested using the t-test. Factors associated with treatment costs were determined using generalized linear models with the log-link function and γ distribution.
Approximately 80% of AF patients were prescribed at least 1 warfarin-potentiating medication while taking warfarin. Patients who used these medications had a 26% higher risk of hemorrhage compared with those who did not use these drugs. Likelihood of hemorrhagic events was significantly increased with the use of potentiating drugs from the following therapeutic classes: anticoagulants (odds ratio [OR] = 1.91), anti-infectives (OR = 1.76), antiplatelets (OR = 1.56), and analgesics (OR = 1.33). The risk also increased when patients took ≥3 therapeutic classes of interacting medications (OR = 1.62–1.85). Among patients with a hemorrhagic event, patients who were prescribed potentiating drugs had higher hemorrhage-related treatment costs ($1359) compared with those patients without prescriptions for warfarin-potentiating drugs ($691; P < 0.001).
Warfarin-potentiating drugs were commonly used among AF patients on warfarin. The use of potentiating drugs increased the risk of a hemorrhage, leading to higher treatment costs. More frequent monitoring or alternative anticoagulant therapies are needed to avoid frequent warfarin drug interactions.
A review of the cost of atrial fibrillation
2012, Value in Health
Citation Excerpt :
Cost estimates for medications and INR testing were drawn from Menzin et al. [40] and included physician costs, with medications accounting for about one-third of the costs. The final single-center study similarly included costs for medications, monitoring costs (including INR fees and overhead costs), and adverse events (bleeds) but not stroke [41]. AF-related medical costs are high, reflecting resource-intensive treatments including anticoagulation treatment.
To systematically review and synthesize the literature on the costs of atrial fibrillation (AF) with attention to study design and costing methods, geography, and intervention approaches.
A systematic search for previously published studies reporting the costs for AF patients was conducted. Data were analyzed in three steps: first by evaluating overall system costs; second by evaluating the relative contribution of specific cost components; and third by examining variations across study designs, across primary treatment approach, and by geography. Finally, a specific review of the treatment costs associated with anticoagulation treatment was examined given the clinical importance and attention given to these costs in the literature.
The literature search resulted in 115 articles. On review of the abstracts or full text of these articles, 21 articles met all study criteria and reported on health system AF-related direct costs. A further six articles focused exclusively on anticoagulation costs for patients with AF. The overall average annual system cost across 27 estimates obtained from the literature was $5450 (SD = $3624) in 2010 Canadian dollars and ranged from a low of $1,632 to a high of $21,099. About one-third of these costs could be attributed to anticoagulation management. The largest cost component was acute care, followed by outpatient and physician and then medication-related costs.
AF-related medical costs are high, reflecting resource-intensive and long-term treatments including anticoagulation treatment. These costs, accompanied with increasing prevalence, justify increased attention to the management of patients with AF. Future studies of AF cost should ensure a broad assessment of the incremental direct medical and societal cost associated with this diagnosis.
The effect of atrial fibrillation on stroke-related inpatient costs in Sweden: A 3-year analysis of registry incidence data from 2001
2008, Value in Health
Atrial fibrillation (AF) is an important risk factor for stroke. It is prevalent in approximately one-fourth of stroke patients, and predictive of worse outcomes. This study aimed to analyze the effect of AF on stroke-related inpatient costs among first-ever stroke patients in Sweden.
Hospitalizations and death records were monitored for 3 years in 6611 first-ever stroke patients. For stroke as primary diagnosis, inpatient costs were calculated on the basis of length of stay at different wards. For stroke as secondary diagnosis, costs were based on diagnosis-related groups.
Patients with AF (24% of all patients) were older (80 years vs. 73 years), had a higher prevalence of hypertension (49% vs. 41%) and/or diabetes (22% vs. 19%), higher risk of experiencing a restroke, and higher case fatality rate (43% vs. 25%) than patients without AF. The average cost per patient over 3 years was €9004, with no statistically significant difference between AF and non-AF patients. However, a multiple regression analysis showed that the presence of AF resulted in higher costs after considering a number of background factors. Among patients surviving the index event, AF patients had on average €818 higher inpatient costs over 3 years than non-AF patients (€10,192 vs. €9374, P < 0.01). The difference in costs was highest for patients aged <65 years, with a difference of €4412 (P < 0.01).
AF-related strokes are associated with higher 3-year inpatient costs than non-AF strokes when controlling for factors such as case fatality rates, other risk factors for stroke, and age.

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Original researchUse of resources and cost implications of stroke prophylaxis with warfarin for patients with nonvalvular atrial fibrillation

Abstract

BMJ

Stroke

Service provision and use of anticoagulants in atrial fibrillation

BMJ

Final results

Circulation

Failure to prescribe warfarin to patients with nonrheumatic atrial fibrillation

J Gen Intern Med.

Medical treatment for stroke prevention

Ann Intern Med.

The value of stroke prevention and treatment

Neurology

Cost-effectiveness of stroke prevention

Br Med Bull.

Systematic review of cost-effectiveness research of stroke evaluation and treatment

Stroke

Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke

Stroke

Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials

Arch Intern Med.

Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials

Arch Intern Med.

The effect of aspirin on the risk of stroke in patients with nonrheumatic atrial fibrillation: The BAATAF Study

Am Heart J.

Original research
Use of resources and cost implications of stroke prophylaxis with warfarin for patients with nonvalvular atrial fibrillation