Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation

doi:10.1016/S0002-9343(00)00440-X

The American Journal of Medicine

Volume 109, Issue 1, 28 July 2000, Pages 45-51

https://doi.org/10.1016/S0002-9343(00)00440-X Get rights and content

Abstract

Purpose: The risk of ischemic stroke varies widely among patients with nonvalvular atrial fibrillation, influencing the choice of prophylactic antithrombotic therapy. We assessed three schemes for stroke risk stratification in these patients who were treated with aspirin and who did not have prior cerebral ischemia.

SUBJECTS AND METHODS: Criteria from three schemes of risk stratification were applied to a longitudinally observed cohort of patients with atrial fibrillation who did not have prior cerebral ischemia and who were treated with aspirin alone or aspirin combined with low, ineffective doses of warfarin in a multicenter clinical trial. The ability of the schemes to identify patients at high (≥6%), low (≤2%), and intermediate annual risks of ischemic stroke was assessed.

RESULTS: During a mean follow-up of 1.8 years, 48 ischemic strokes occurred among 1,073 patients with atrial fibrillation who were taking aspirin (rate = 2.5 per 100 person-years). Each of the three schemes predicted stroke and disabling stroke, and successfully identified patients at low risk (observed stroke rates of 0.3 to 1.1 per 100 person-years), although the fractions of the cohort that were categorized as low risk varied from 14% to 45%. The observed rates of ischemic stroke among patients categorized as high risk ranged from 3.5 to 7.2 per 100 person-years among the stratification schemes. Two schemes considered all patients >75 years old as high risk (observed stroke rate 4.2 per 100 person-years), while the remaining scheme classified one third of patients in this age group as low risk (observed stroke rate 0.6 per 100 person-years).

CONCLUSIONS: When tested in a large cohort of patients with atrial fibrillation who were treated with aspirin, available risk-stratification schemes successfully identified patients with low rates of ischemic stroke, but less consistently identified high-risk patients.

Section snippets

Risk-stratification schemes

We considered three sets of criteria for stratifying patients by their risk of ischemic stroke (Table 1). The criteria of the Atrial Fibrillation Investigators (AFI) were based on a multivariate pooled analysis of 1,593 participants who were assigned to placebo or to avoid anticoagulation in five randomized trials (8). During a mean follow-up of 1.4 years, 106 ischemic strokes occurred (Table 2). The AFI scheme divided patients into two strata: low risk and all others (combining intermediate

Results

Clinical features of the two cohorts from which the AFI and SPAF schemes were derived were similar, and characteristics of the SPAF-III test cohort were similar to the derivation cohorts (Table 2). Exclusion of 109 (9%) patients with prior stroke or transient ischemic attack contributed to a lower stroke rate (2.5 per 100 person-years) in the SPAF-III test cohort compared with the derivation cohorts (Table 2). During a mean follow-up of 1.8 years, 48 ischemic strokes occurred, of which 22 (46%)

Discussion

The relative efficacy and safety of warfarin and aspirin for prevention of stroke in patients with atrial fibrillation are well established (1). Accurate prediction of stroke risk, so that patients receive the most appropriate antithrombotic management, has become the salient clinical issue. We evaluated three risk-stratification schemes for the prediction of initial ischemic stroke in patients with nonvalvular atrial fibrillation. Although each scheme was able to classify low-, intermediate-,

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Cited by (95)

Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline
2022, Chest
Citation Excerpt :
This involves estimating the risk for ATE, encompassing stroke and systemic embolism for patients with atrial fibrillation or a mechanical heart valve, and the risk for recurrent VTE for patients with a history of VTE with perioperative interruption of anticoagulant drugs. The risk classification in Table 1 is empiric and separates patients according to estimated risk for ATE (high risk: > 10%/year; intermediate risk: 4%-10%/year; low risk: < 4%/year) and estimated risk for VTE (high risk: > 10%/month; intermediate risk: 4%-10%/month; low risk: < 2%/month); it is derived mainly from studies in a non-perioperative setting that involved patients with atrial fibrillation,29-32 a mechanical heart valve,33-35 or VTE36-38 who were not receiving anticoagulant therapy (eg, placebo instead of a VKA in patients with atrial fibrillation) or less effective antithrombotic therapy (eg, ASA instead of a VKA in patients with a mechanical heart valve).13,14,25 A perioperative risk classification for patients with coronary artery disease, particularly if they have coronary stents, is available elsewhere and is also empiric.39,40
The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug.
Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines.
A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures.
Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.
Risk Prediction for Ischemic Stroke and Transient Ischemic Attack in Patients Without Atrial Fibrillation: A Retrospective Cohort Study
2017, Journal of Stroke and Cerebrovascular Diseases
Stroke mainly occurs in patients without atrial fibrillation (AF). This study explored risk prediction models for ischemic stroke and transient ischemic attack (TIA) in patients without AF.
Three US-based healthcare databases (Truven MarketScan Commercial Claims and Encounters [CCAE], Medicare Supplemental [MDCR], and Optum Clinformatics [Optum]) were used to establish patient cohorts without AF during the index period of 2008-2012. The performance of 2 existing models (CHADS₂ and CHA₂DS₂-VASc) for predicting stroke and TIA was examined by fitting a logistic regression to a training dataset and evaluating predictive accuracy in a validation dataset (area under the curve, AUC) using patients with complete follow-up of 1 or 3 years, separately.
The commercial populations were younger and had fewer comorbidities than Medicare-eligible population. The incidence proportions of ischemic stroke and TIA during 1 and 3 years of follow-up were .5% and 1.9% (CCAE), .6% and 2.2% (Optum), and 4.6% and 13.1% (MDCR), respectively. The models performed consistently across all 3 databases, with the AUC ranging from .69 to .77 and from .68 to .73 for 1- and 3-year prediction, respectively. Predictive accuracy was lower than the initial work of CHADS₂ evaluation in patients with AF (AUC: .82), but consistent with a subsequent meta-analysis of CHADS₂ (.60-.80) and CHA₂DS₂-VASc performance (.64-.79).
Although the existing schemes for predicting ischemic stroke and TIA in patients with AF can be applied to patients without AF with comparable predictive accuracy, the evidence suggests that there is room for improvement in these models' performance.
The C of CHADS: Historical perspective and clinical applications for anticoagulation in patients with non valvular atrial fibrillation and congestive heart failure
2016, International Journal of Cardiology
The risk stratification of patients with coexisting non valvular atrial fibrillation and congestive heart failure, is often a clinical challenge, as the definitions of congestive heart failure in the popular CHADS2 and CHA2DS2VASc scoring systems, and amongst major clinical trials on Warfarin and Novel Oral Anticoagulants (NOAC) have heterogeneity. Available evidence reveals that any heart failure and/or left ventricular systolic dysfunction is associated with higher rates of stroke/systemic embolism and bleeding in patients with non valvular atrial fibrillation compared to patients without heart failure and normal left ventricular function. Most standard dose NOAC regimens have a better safety and efficacy profile over warfarin in most heart failure sub-group types with a few exceptions including patients with NYHA III/IV on Dabigatran 150 mg BID from the RE-LY trial, who had higher major bleeding events, and patients with asymptomatic left ventricular dysfunction (ejection fraction ≤ 40%) and heart failure with reduced ejection fraction on 20 mg of Rivaroxaban in the ROCKET-AF trial, when compared to patients on Warfarin in the corresponding groups. With the gaining popularity and use of NOACs, understanding their safety profile in such situations is paramount.
Comparison of the reliability and validity of four contemporary risk stratification schemes to predict thromboembolism in non-anticoagulated patients with atrial fibrillation
2013, International Journal of Cardiology
The risk of thromboembolic (TE) complications in atrial fibrillation (AF) patients is not homogeneous. Risk schemes can help target anticoagulant therapy for patients at highest risk of TE complications.
To test the predictive ability of 4 risk schemes: The Framingham, the 8th ACCP, the ACC/AHA/ESC 2006, and the CHA₂DS₂-VASc.
186 patients with non-valvular AF and off anticoagulant therapy were included. All subjects who experienced a stroke, transient ischemic attack, or peripheral embolism were identified. Each schema was divided into low, intermediate, and high-risk categories. Discrimination was assessed via the c-statistic.
We identified 10 TE events that occurred during 668 person-years off anticoagulation therapy. All risk schemes had fair discriminating ability (c-statistic ranged from 0.59 [for CHA₂DS₂-VASc] to 0.73 [for Framingham]). The proportion of patients assigned to individual risk categories varied widely across schemes. CHA₂DS₂-VASc categorized the fewest patients into low and intermediate-risk categories, whereas the Framingham schema assigned the highest patients into low-risk strata. There were no TE events in the low and intermediate-risk categories using CHA₂DS₂-VASc, whereas the most schemes assigned patients into intermediate-risk category had a event rate ranging from 2.5 (ACC/AHA/ESC and 8th ACCP schemes) to 6% (Framingham). The negative predictive value of TE events was of 100% for the no high-risk patients using CHA₂DS₂-VASc.
Compared to ACC/AHA/ESC, 8th ACCP, and Framingham, CHA₂DS₂-VASc risk stratification schema may be better in discriminating between patients at a low and intermediate risk of TE complications.
Perioperative management of antithrombotic therapy. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines
2012, Chest
This guideline addresses the management of patients who are receiving anticoagulant or antiplatelet therapy and require an elective surgery or procedure.
The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement.
In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recommend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require noncardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery > 6 weeks after bare-metal stent placement and > 6 months after drug-eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C).
Perioperative antithrombotic management is based on risk assessment for thromboembolism and bleeding, and recommended approaches aim to simplify patient management and minimize adverse clinical outcomes.
Secondary prevention of cardioembolic stroke
2011, Stroke: Pathophysiology, Diagnosis, and Management

View all citing articles on Scopus

^☆: Supported by a grant (NS 24224) from the Division of Stroke and Trauma, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.

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Special articleAssessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation☆

Abstract

Section snippets

Risk-stratification schemes

Results

Discussion

Chest

Am J Med

Antithrombotic therapy to prevent stroke in patients with atrial fibrillationa meta-analysis

Ann Intern Med

Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillationthe Stroke Prevention in Atrial Fibrillation III randomised clinical trial

Lancet

Secondary prevention of vascular events in patients with nonrheumatic atrial fibrillation and recent transient ischemic attack or minor ischemic stroke

Lancet

Patients with nonvalvular atrial fibrillation at low-risk of stroke during treatment with aspirin

JAMA

Primary prevention of arterial thromboembolism in nonrheumatic atrial fibrillation in primary carerandomised controlled trial comparing two intensities of coumarin with aspirin

BMJ

Stroke risk in an elderly population with atrial fibrillation

J Gen Intern Med

Atrial fibrillation and thromboembolisma decade of progress in stroke prevention

Ann Intern Med

Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillationanalysis of pooled data from five randomized clinical trials

Arch Intern Med

Predictors of ischemic stroke during aspirin therapy in atrial fibrillationanalysis of 2012 participants in the SPAF I-III clinical trials

Stroke

Echocardiographic predictors of stroke in patients with atrial fibrillationa prospective study of 1,066 patients from three clinical trials

Arch Intern Med

Predictors of thromboembolism in atrial fibrillationI. Clinical features of patients at risk

Ann Intern Med

Special article
Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation☆