Self-Reported Race as a Social Determinant of Stroke Risk in Observational Versus Clinical Trial Datasets

Abstract Funding Acknowledgements Type of funding sources: None. Background Recently, CARS was proposed to predict 1-year absolute stroke risk in non-anticoagulated patients with atrial fibrillation (AF). We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients. Methods We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS was estimated for each patient using an estimated 64% risk reduction with anticoagulation. Results 3,503 patients were included (2,205 [62.9%] clinical trial and 1,298 [37.1%] real-world). In the clinical trial cohort, the median age was 71 (IQR 65-77) and CHA2DS2-VASc score 3 (IQR 2-4). In the real-world cohort, the median age was 76 (IQR 70-81) and CHA2DS2-VASc score 4 (IQR 3-5). At 1-year, there were 40 and 31 stroke events in the clinical trial and real-world cohorts, respectively. Average predicted residual stroke risk by mCARS was identical to actual stroke risk (1.8 [±1.8%] vs. 1.8% [95% CI, 1.3-2.4]) in the clinical trial, and broadly similar in the real-world (2.1 [±1.9%] vs. 2.4% [95% CI, 1.6-3.4]). Additionally, these values were comparable across the subgroups stratified by CHA2DS2-VASc score in both cohorts. AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598-0.758) and 0.712 (95% CI, 0.618-0.805), respectively. In an exploratory analysis, we found that mCARS was able to refine stroke risk estimation for each point of the CHA2DS2-VASc score in both cohorts. Conclusion Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS. Such patients with high residual stroke risk may benefit from more aggressive interventions and follow-up. Absolute 1-year stroke risk Clinical Trial Real-World Median (IQR) Range Median (IQR) Range CHA2DS2-VASc score 0 NA 0.9 (0.6 - 1.3) 0.2 - 1.4 CHA2DS2-VASc score 1 1.1 (0.7 - 1.4) 0.2 - 2.0 1.4 (0.9 - 1.7) 0.2 - 13.0 CHA2DS2-VASc score 2 2.0 (1.5 - 2.4) 0.3 - 10.8 2.1 (1.5 - 2.6) 0.3 - 10.8 CHA2DS2-VASc score 3 2.6 (2.1 - 3.4) 0.4 - 13.3 2.8 (2.5 - 3.4) 0.9 - 13.3 CHA2DS2-VASc score 4 3.6 (2.8 - 5.6) 0.3 - 18.1 3.9 (3.3 - 5.0) 1.1 - 21.0 CHA2DS2-VASc score 5 6.7 (3.6 - 14.0) 1.9 - 20.9 4.8 (3.9 - 12.2) 1.2 - 21.0 CHA2DS2-VASc score 6 13.6 (5.5 - 15.8) 2.4 - 21.8 12.8 (4.8 - 16.7) 2.2 - 21.8 CHA2DS2-VASc score 7 15.7 (14.5 - 17.4) 4.5 - 21.9 15.6 (5.9 - 17.5) 4.1 - 23.5 CHA2DS2-VASc score 8 16.5 (14.0 - 18.5) 13.1 - 20.3 16.9 (15.7 - 19.5) 13.6 - 21.0 IQR, interquartile range; NA, not applicable.

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Number needed to treat for net effect of anticoagulation in atrial fibrillation

EP Europace ◽

10.1093/europace/euab116.276 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

WY Ding ◽

JM Rivera-Caravaca ◽

F Marin ◽

G Li ◽

V Roldan ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trial ◽

Major Bleeding ◽

Real World ◽

Stroke Risk ◽

Absolute Risk ◽

Baseline Risk ◽

Number Needed To Treat ◽

Bleeding Events ◽

Risk Increase

Abstract Funding Acknowledgements Type of funding sources: None. Background The benefit of oral anticoagulation (OAC) in atrial fibrillation (AF) must be balanced against any potential risk of harm. We aimed to evaluate the "NNT for net effect" (NNTnet) using CARS in anticoagulated patients with AF. Methods We used patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial. Baseline risk of stroke was calculated using CARS while major bleeding was estimated from prior studies. Stroke and major bleeding events at 1-year were determined. NNTnet was calculated as a reciprocal of the net effect of ARR with OAC (NNTnet= 1 / (ARRstroke - ARIbleeding)). Results 3,511 patients were included (1,306 [37.2%] real-world patients and 2,205 [62.8%] clinical trial). The absolute 1-year stroke risk was similar across both cohorts and the main results are presented in the Table. In both cohorts, the NNTnet was significantly lower in patients with an excess stroke risk of ≥2% by CARS. Among real-world patients with a very high (>10%) baseline stroke risk, the use of OAC was associated with an ARRstroke of 10.9% and ARIbleeding of 1.2%, generating an overall NNTnet of 11. In the clinical trial, the use of OAC was associated with an ARRstroke of 11.0% and ARIbleeding of 0.6%, generating an overall NNTnet of 10. Conclusion Overall, the NNTnet approach in AF incorporates information regarding baseline risk of stroke and major bleeding, and relative effects of OAC with the potential to include multiple additional outcomes and weighting of events based on their perceived effects by individual patients. This simple and intuitive metric may be useful to improve communication and optimise the patient-centred management of AF. NNT in Real-World and Clinical Trial Real-World Clinical Trial Ischaemic stroke risk at 1-year Baseline risk without anticoagulation (%) 5.7% (95% CI 5.5 - 6.0) 5.1% (95% CI 4.9 - 5.3) Anticoagulation-mediated risk (%) 1.7% (95% CI 1.1 - 2.6) 1.3% (95% CI 0.8 - 1.8) Absolute risk reduction (%) 4.0% 3.8% NNTbenefit 25 27 Major bleeding risk at 1-year Baseline risk without anticoagulation (%) 2.3% 2.3% Anticoagulation-mediated risk (%) 3.3% (95% CI 2.4 - 4.4) 3.9% (95% CI 3.1 - 4.8) Absolute risk increase (%) 1.0% 1.6% NNTharm 100 63 NNTnet 34 46

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Prediction of Residual Stroke Risk in Anticoagulated Patients with Atrial Fibrillation: mCARS

Journal of Clinical Medicine ◽

10.3390/jcm10153357 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3357

Author(s):

Wern Yew Ding ◽

José Miguel Rivera-Caravaca ◽

Francisco Marin ◽

Christian Torp-Pedersen ◽

Vanessa Roldán ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trial ◽

Real World ◽

Stroke Risk ◽

Risk Estimation ◽

Absolute Risk ◽

Oral Anticoagulants ◽

Absolute Risk Reduction ◽

The Real ◽

Anticoagulated Patients

Our ability to evaluate residual stroke risk despite anticoagulation in atrial fibrillation (AF) is currently lacking. The Calculator of Absolute Stroke Risk (CARS) has been proposed to predict 1-year absolute stroke risk in non-anticoagulated patients. We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients from ‘real-world’ and ‘clinical trial’ cohorts. We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS were estimated for each patient. None of the patients were treated with non-vitamin K antagonist oral anticoagulants. The predicted residual stroke risk was compared to actual stroke risk. 3503 patients were included (2205 [62.9%] clinical trial and 1298 [37.1%] real-world). There was wide variation of CARS for each category of CHA2DS2-VASc score in both cohorts. Average predicted residual stroke risk by mCARS (1.8 ± 1.8%) was identical to actual stroke risk (1.8% [95% CI, 1.3–2.4]) in the clinical trial, and broadly similar in the real-world (2.1 ± 1.9% vs. 2.4% [95% CI, 1.6–3.4]). AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598–0.758) and 0.712 [95% CI, 0.618–0.805], respectively. mCARS was able to refine stroke risk estimation for each point of the CHA2DS2-VASc score in both cohorts. Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS, thereby allowing an assessment of the absolute risk reduction of treatment and facilitating a patient-centred approach in the management of AF. Such identification of patients with high residual stroke risk could help target more aggressive interventions and follow-up.

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Stroke risk based on classification of atrial fibrillation: real-world vs clinical trial

European Heart Journal ◽

10.1093/eurheartj/ehab724.0470 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

W.Y Ding ◽

J.M Rivera-Caravaca ◽

F Marin ◽

V Roldan ◽

G.Y.H Lip

Keyword(s):

Atrial Fibrillation ◽

Clinical Trial ◽

Incidence Rate ◽

Real World ◽

Stroke Risk ◽

Clinical Classification ◽

Temporal Rhythm ◽

Anticoagulated Patients ◽

Trial Participants

Abstract Background The most widely accepted clinical classification of atrial fibrillation (AF) is according to temporal rhythm-based patterns, reflecting the notion that most patients initially suffer from transient episodes that prolong over time due to atrial substrate remodelling as the disease progresses. Therefore, it may be speculated that patients with extended episodes of “continuous” AF (persistent, long-standing persistent and permanent AF) may be at higher risk of stroke complications compared to paroxysmal AF (pAF). However, the risk of stroke according to clinical classification of AF remains poorly defined. In this study, we assessed the impact of AF type on stroke risk in patients with AF from “real-world” and “clinical trial” cohorts. Methods Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. All patients were anticoagulated. Patients were grouped into those with pAF and non-pAF. pAF was defined as AF that terminates spontaneously or with intervention within seven days of onset. Non-pAF was defined as AF that lasted longer than seven days, including persistent, long-standing persistent and permanent AF subtypes. Study endpoint was the incidence rate of ischaemic stroke. A modified CHA2DS2-VAS“c” score that applied one additional point for a “c” criterion of continuous AF (i.e. non-pAF) was calculated. Results 5,917 patients were included; 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Real-world patients had a median age of 76 (interquartile range [IQR] 71–81) years with 51.3% females compared to a median age of 71 (IQR 64–77) years with 33.5% females among clinical trial participants. Baseline demographics were comparable in both groups in the real-world cohort but clinical trial participants with non-pAF were older, predominantly male and had more comorbidities compared to those with pAF. Crude stroke rates were comparable between the groups in real-world patients (incidence rate ratio [IRR] 0.72 [95% CI, 0.37–1.28], p=0.259) though clinical trial participants with non-pAF (vs. pAF) had a significantly higher crude rate of stroke events (IRR 4.66 [95% CI, 2.41–9.48], p<0.001). Using multivariable cox regression analysis, AF type was not independently associated with stroke risk in the real-world (adjusted hazard ratio [HR] 1.41 [95% CI, 0.80–2.50], p=0.239) and clinical trial (adjusted HR 1.17 [95% CI, 0.62–2.20], p=0.621) cohorts, after accounting for known risk factors using the CHA2DS2-VASc score. Using receiver operating characteristic curves analysis, we found no significant improvement in the CHA2DS2-VAS“c” compared to CHA2DS2-VASc score in either cohort (p>0.05). Conclusion Overall, there was no association between the temporal rhythm-based patterns of AF and stroke risk among anticoagulated patients, suggesting that this should not be a consideration when assessing the need for anticoagulation in AF. FUNDunding Acknowledgement Type of funding sources: None.

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