The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med

Massachusetts General Hospital, Boston, Massachussetts 02114, USA.
Annals of internal medicine (Impact Factor: 17.81). 10/2009; 151(5):297-305.
Source: PubMed


Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage.
To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation.
Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003.
An integrated health care delivery system.
13 559 adults with nonvalvular atrial fibrillation.
Warfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism.
Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used.
Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable.
Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation.
National Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

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    • "A high CHADS2 score correspond to a higher risk of stroke. Well known risk factors for stroke in patients with AF are congestive heart failure, hypertension, age N 75 years, diabetes, previous stroke and transient ischemic attack [8] [9] [10] [11]. Each factor is given one point, except for stroke, which is given two points. "
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    ABSTRACT: We aimed to study differences in the prescribing of warfarin, aspirin and statins to patients with atrial fibrillation (AF) in socio-economically diverse neighborhoods. We also aimed to explore the effects of neighborhood deprivation on the relationship between CHADS2 risk score and warfarin prescription. Data were obtained from primary health care records that contained individual clinical data that were linked to national data on neighborhood of residence and a deprivation index for different neighborhoods. Logistic regression was used to estimate the potential neighborhood differences in prescribed warfarin, aspirin and statins, and the association between the CHADS2 score and prescribed warfarin treatment, in neighborhoods with high, middle (referent) and low socio-economic (SES). After adjustment for age, socio-economic factors, co-morbidities and moves to neighborhoods with different SES during follow-up, adults with AF living in high SES neighborhoods were more often prescribed warfarin (men odds ratio (OR) (95% confidence interval (CI): 1.44 (1.27-1.62); and women OR (95% CI): 1.19 (1.05-1.36)) and statins (men OR (95% CI): 1.23 (1.07-1.41); women OR (95% CI): 1.23 (1.05-1.44)) compared to their counterparts residing in middle SES. Prescription of aspirin was lower in men from high SES neighborhoods (OR (95% CI): 0.75 (0.65-0.86)) than in those from middle SES neighborhoods. Higher CHADS2 risk scores were associated with higher warfarin prescription which remained after adjustment for neighborhood SES. The apparent inequalities in pharmacotherapy seen in the present study call for resource allocation to primary care in neighborhoods with low and middle socio-economic status. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 04/2015; 187(1):547-552. DOI:10.1016/j.ijcard.2015.04.005 · 4.04 Impact Factor
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    • "We used weighting of 1.0 for both VTE and bleeding in primary net clinical benefit analysis. We performed sensitivity analyses using different weighting according to the method of Singer et al. [16], allocating bleeding a weight of 1.5 relative to a VTE or allocating VTE a weight of 1.5 relative to a bleeding event. Accordingly, adjusted risk differences and net clinical benefit estimates were calculated in the cohort of THR with standard and extended durations of thromboprophylaxis. "
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    ABSTRACT: Clinical trials have provided evidence about efficacy and safety of extended thromboprophylaxis among total hip replacement (THR) patients. There is a lack of evidence on effectiveness and safety of extended treatment in unselected patients from routine clinical practice. We examined the effectiveness and safety of short (1-6 days) and standard (7-27 days) compared with extended (≥28days) thromboprophylaxis using population-based design. Among all primary THR procedures performed in Denmark from 2010 through 2012 (n=16,865), we calculated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for risk of symptomatic venous thromboembolism (VTE) and major bleeding, in addition to net clinical benefit, defined as the number of VTE avoided minus the number of excess bleeding events occurring among patients prescribed short-term and standard versus extended treatment. The 90-day risks of VTE were 1.1% (short), 1.4% (standard), and 1.0% (extended), yielding aHRs of 0.83 (95% CI: 0.52-1.31) and 0.82 (95% CI: 0.50-1.33) for short and standard versus extended treatment. The risk of major bleeding was 1.1% (short), 1.0% (standard), and 0.7% (extended), resulting in aHRs of 1.64 (95% CI: 0.83-3.21) and 1.24 (95%CI: 0.61-2.51) for short and standard versus extended thromboprophylaxis. Direct comparison between benefits and harms using net clinical benefit analyses did not favor any of the three treatment durations. The same results were found for VTE or death. In a real-word observational cohort of unselected THR patients, we observed no difference in the risks of symptomatic VTE, VTE/ death or bleeding with respect to thromboprophylaxis duration. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 12/2014; 135(2). DOI:10.1016/j.thromres.2014.11.029 · 2.45 Impact Factor
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    • "Given the dramatic difference in the consequences of intracranial bleeding and nonintracranial bleeding, other studies examining the net clinical benefit of OAC have focused on the risk of intracranial hemorrhage (ICH) caused by OAC rather than all major bleeding.11,12 As clinicians may be primarily concerned with the increased risk of ICH, we performed a sensitivity analysis using an alternate definition of net clinical benefit as follows: "
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    ABSTRACT: Objectives: Atrial fibrillation (AF), the most common arrhythmia in elderly patients, accounts for 15% of strokes. Oral anticoagulation (OAC) can reduce the risk of stroke by 60% but is underprescribed. The HAS-BLED score (Hypertension, Abnormal renal or liver function, Stroke, Bleeding, Labile INR, Elderly, Drugs) can predict OAC bleeding complications. The authors hypothesized that use of HAS-BLED can help align decision making with current evidence. Methods: The authors developed a survey with four clinical vignettes designed to highlight the complexity in deciding whether to anticoagulate elderly patients with AF. Physicians were randomly assigned to receive the survey either including the HAS-BLED score and the estimated annual risk of bleeding (intervention) or without (control). Following each vignette, participants were asked: (1) whether they would recommend OAC and (2) to estimate the risk of bleeding and stroke. The “appropriate” anticoagulation decision was defined as the choice that minimized the risk of stroke and major bleeding. Results: A total of 203 physicians were recruited for the survey, with 55 responses obtained (27%). Physicians who were given the HAS-BLED score were 18% more likely to choose appropriate anticoagulation (74% vs. 56%, P < .05). The HAS-BLED score assisted physicians in both choosing to anticoagulate when appropriate and not to anticoagulate when the risk of bleeding outweighed the benefit. Overall, physicians were poor at estimating the risk of stroke (42% correct) and major bleeding (31% correct). Conclusions: Presentation of the HAS-BLED score led to an 18% improvement in appropriate OAC choices. Future study should evaluate incorporation of HAS-BLED use in real-time clinical situations.
    Critical Pathways in Cardiology 09/2014; 13(3):109-13. DOI:10.1097/HPC.0000000000000017
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