Identifying patients with atrial fibrillation and "truly - - PowerPoint PPT Presentation

www.tri-london.ac.uk The GARFIELD Registry is funded by an unrestricted research grant from Bayer Pharma AG

Identifying patients with atrial fibrillation and "truly low" thromboembolic risk who are poorly characterized by CHA2DS2-VASc: Superior performance of a novel machine-learning tool in GARFIELD-AF

Keith A.A. Fox, Joseph E. Lucas, Karen S. Pieper, Jean-Pierre Bassand, A. John Camm, David A. Fitzmaurice, Werner Hacke, Gloria Kayani, Ali Oto, Ajay K. Kakkar for the GARFIELD-AF Investigators

www.tri-london.ac.uk

Background and Context

10 20 30 40 50 60 70 80 90 100 Cohort 1 2010–11 (n=5311) Cohort 2 2011–13 (n=11,562) Cohort 3 2013–14 (n=11,343) Cohort 4 2014–15 (n=10,923)

Proportion of patients, %

VKA VKA+AP FXaI FXaI+AP DTI DTI+AP AP None

Camm AJ et al. Heart 2016 (in press)

• The role of anticoagulation for patients with AF and ≥ 1 risk factor for stroke/systemic

embolism is defined by trial evidence and guidelines

• Between 2010-2011 and 2014-2015, anticoagulation usage rose from 57% to 71% of

patients with AF

• However, the balance of risk and benefit is poorly defined for “low risk’ AF

www.tri-london.ac.uk

How are low and high risk AF patients managed in practice?

• Contrary to international guideline recommendations,

– 28% high-risk patients (CHA2DS2-VASc ≥2) are not anticoagulated

1 ≥2 CHA2DS2-VASc 10 20 30 40 50 60 70 80 90 100 (n=352) (n=1336) (n=9027) Proportion of patients, %

None AP DTI+AP DTI FXaI+AP FXaI VKA+AP VKA

– 51% of very low-risk patients (CHA2DS2-VASc 0) are anticoagulated

Camm AJ et al. Heart 2016 (in press)

www.tri-london.ac.uk

How are low and high risk AF patients managed in practice?

• Contrary to international guideline recommendations,

– 28% high-risk patients (CHA2DS2-VASc ≥2) are not anticoagulated

1 ≥2 CHA2DS2-VASc 10 20 30 40 50 60 70 80 90 100 (n=352) (n=1336) (n=9027) Proportion of patients, %

None AP DTI+AP DTI FXaI+AP FXaI VKA+AP VKA

– 51% of very low-risk patients (CHA2DS2-VASc 0) are anticoagulated

Camm AJ et al. Heart 2016 (in press)

Factors beyond those in current risk scores appear to influence prescribing decisions on anticoagulation, including risk of bleed

www.tri-london.ac.uk

Purpose: To provide accurate estimates of risk as the basis

• f decisions on prescribing or withholding anticoagulation

Aim: To derive and validate a more accurate and user- friendly method of stratifying patients according to risks of death, stroke and bleeding

www.tri-london.ac.uk

Statistical Methods: The GARFIELD Score A “machine learning” approach to risk modelling

• Coalescent regression avoids the need to specify levels of relatedness in

the statistical model, it allows joint modeling of all outcomes.

• Models were based on 38984 patients in GARFIELD 2010 to 2015 for:

– all-cause mortality, – ischaemic stroke/thromboembolism, and – haemorrhagic stroke/major bleed

that occurred within 1-year of enrolment into GARFIELDAF.

• Also, a simplified model was also derived to facilitate web applications
• The performance of both models were compared with CHA2DS2-VASc in all

patients and those with a low risk of stroke

• External validation was undertaken using an independent contemporary

registry ORBIT-AF

www.tri-london.ac.uk

Number of events in low- and higher-risk patients at 1 year

Event Low risk* (n=7 861; 20.2%) Higher risk

(n=31 123)

All-cause mortality 94 (1.4%) 1387 (4.9%) Ischaemic stroke/ Systemic embolism 35 (0.5%) 396 (1.4%) Haemorrhagic stroke/ Major bleed 26 (0.4%) 295 (1.1%)

Number of events determined using one year Kaplan-Meier rates

• Low risk patients (defined as CHA2DS2-VASc 0 or 1 for men and 1 or 2 for women) represent

20.2% of overall cohort

• Total number of patients: 38,984 enrolled between March 2010 and July 2015

www.tri-london.ac.uk

GARFIELD Score performance characteristics in all patients

C statistic: 0.78 C statistic: 0.63 C statistic: 0.67

All-cause mortality Ischaemic stroke / Systemic embolism Haemorrhagic stroke / Major bleed

www.tri-london.ac.uk

Comparison of GARFIELD Score with CHA2DS2-VASc in all patients

Performance measure Event GARFIELD Score CHA2DS2-VASc C statistic All-cause mortality 0.78 0.66 Ischaemic stroke / systemic embolism 0.63 0.63 Haemorrhagic stroke / major bleed 0.67 0.61

www.tri-london.ac.uk

Comparison of GARFIELD Score with CHA2DS2-VASc in low-risk patients CHA2DS2-VASc 0 or 1 for men and 1 or 2 for women

Performance measure Events GARFIELD Score CHA2DS2-VASc C statistic All-cause mortality 0.72 0.56 Ischaemic stroke / Systemic embolism 0.62 0.56 Haemorrhagic stroke / Major bleed 0.72 0.57

www.tri-london.ac.uk

Performance of the new simplified GARFIELD Score in patients enrolled in GARFIELD-AF and ORBIT-I

Population Endpoint C Statistic (95% CI) Events (n / N) GARFIELD-AF Ischaemic stroke/SE 0.70 (0.68, 0.73) 438 / 38,607 ORBIT-I Any stroke/SE 0.69 (0.64, 0.75) 91 / 9,743 GARFIELD-AF Haemorrhagic stroke/major bleed 0.68* (0.64, 0.72) 187 / 12,249 1 ORBIT-I Major bleed 0.61 (0.58-0.64) 625 / 7,442

• 1. Evaluation of a subset of patients who were prescribed oral anticoagulants in countries where at least 1% bleeding rate was recorded

*C statistic for HAS-BLED is 0.64 (95% CI 0.59, 0.68)

www.tri-london.ac.uk

Conclusions

• Performance of GARFIELD Score was superior

to CHA2DS2-VASc in predicting ischaemic stroke

• r major bleed in all patients, and those with a

low risk of stroke

• This integrated risk tool has the potential for

incorporation in routine electronic systems

www.tri-london.ac.uk

Next steps

• A simplified GARFIELD Score, validated using

data from ORBIT-AF, is being developed, with web-based and mobile device applications*

• The GARFIELD Score may help physicians

assess the appropriateness of anticoagulation in low-risk patients *http://colab-sbx-322.oit.duke.edu:3338/

20% Risk of major bleed in 1 year BLEEDING SCORE