Stroke and Thromboembolism in Warfarin-Treated Patients with Atrial Fibrillation: Comparing the CHA₂DS₂-VASc and GARFIELD-AF Risk Scores

Abstract

Background Evaluation of thromboembolic risk is essential in anticoagulated atrial fibrillation (AF) patients. The CHA₂DS₂-VASc score is largely validated and recommended by most guidelines. The GARFIELD-AF Stroke score has been proposed as an alternative risk score.

Methods We analyzed warfarin-treated patients from SPORTIF III and V studies. Any thromboembolic event (TE) was an adjudicated study outcome. We compared the two scores' capacity in predicting any TE occurrence.

Results A total of 3,665 patients (median [interquartile range] age: 72 [66–77] years; 30.5% female) were included in this analysis. After a mean (standard deviation) follow-up of 566.3 (142.5) days, 148 (4.03%) TEs were recorded. Both continuous CHA₂DS₂-VASc and GARFIELD-AF were associated with TE (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.22–1.53 and HR: 2.43, 95% CI: 1.72–3.42), with modest predictive ability (c-indexes: 0.63, 95% CI: 0.59–0.68 and 0.61, 95% CI: 0.56–0.66, respectively), with no differences. CHA₂DS₂-VASc quartiles showed an increasing cumulative risk, while in GARFIELD-AF only the highest quartile (Q4) demonstrated an increased TE risk. On multivariate Cox regression analysis, CHA₂DS₂-VASc quartiles were associated with increasing risk of TE, whereas for GARFIELD-AF only Q4 showed an association with TE. Discrimination analysis showed that GARFIELD-AF quartiles were associated with a 48.7% reduction in discriminatory ability. Using decision curve analysis, CHA₂DS₂-VASc was associated with improved clinical usefulness and net clinical benefit, compared with GARFIELD-AF.

Conclusion In a warfarin-treated trial cohort of AF patients, both CHA₂DS₂-VASc and GARFIELD-AF Stroke scores were associated with adjudicated TE events, with modest predictive capacity. The simpler CHA₂DS₂-VASc score improved discriminatory capacity compared with the more complex GARFIELD-AF score, demonstrating improved clinical usefulness and net clinical benefit.

Keywords

atrial fibrillation - risk scores - thromboembolic events

• References

• 1 Lip G, Freedman B, De Caterina R, Potpara TS. Stroke prevention in atrial fibrillation: past, present and future. Comparing the guidelines and practical decision-making. Thromb Haemost 2017; 117 (07) 1230-1239
• 2 Proietti M, Lane DA, Boriani G. et al. Stroke prevention, evaluation of bleeding risk, and anticoagulant treatment management in atrial fibrillation contemporary international guidelines. Can J Cardiol 2019; 35 (05) 619-633
• 3 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140 (02) e125-e151
• 4 Lip GYH, Banerjee A, Boriani G. et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018; 154 (05) 1121-1201
• 5 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2020;
• 6 Fanola CL, Giugliano RP, Ruff CT. et al. A novel risk prediction score in atrial fibrillation for a net clinical outcome from the ENGAGE AF-TIMI 48 randomized clinical trial. Eur Heart J 2017; 38 (12) 888-896
• 7 Oldgren J, Hijazi Z, Lindbäck J. et al; RE-LY and ARISTOTLE Investigators. Performance and validation of a novel biomarker-based stroke risk score for atrial fibrillation. Circulation 2016; 134 (22) 1697-1707
• 8 Fox KAA, Lucas JE, Pieper KS. et al; GARFIELD-AF Investigators. Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation. BMJ Open 2017; 7 (12) e017157
• 9 Borre ED, Goode A, Raitz G. et al. Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review. Thromb Haemost 2018; 118 (12) 2171-2187
• 10 Proietti M, Mujovic N, Potpara TS. Optimizing stroke and bleeding risk assessment in patients with atrial fibrillation: a balance of evidence, practicality and precision. Thromb Haemost 2018; 118 (12) 2014-2017
• 11 Kakkar AK, Mueller I, Bassand JP. et al. International longitudinal registry of patients with atrial fibrillation at risk of stroke: Global Anticoagulant Registry in the FIELD (GARFIELD). Am Hear J 2012; 163 (01) 13.e1-19.e1
• 12 Dalgaard F, Pieper K, Verheugt F. et al. GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study. BMJ Open 2019; 9 (11) e033283
• 13 Halperin JL. Executive Steering Committee, SPORTIF III and V Study Investigators. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Am Heart J 2003; 146 (03) 431-438
• 14 Olsson SB. Executive Steering Committee of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003; 362 (9397): 1691-1698
• 15 Albers GW, Diener H-C, Frison L. et al; SPORTIF Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005; 293 (06) 690-698
• 16 Lip GYH, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (02) 263-272
• 17 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44 (03) 837-845
• 18 Pencina MJ, D'Agostino Sr RB, D'Agostino Jr RB, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27 (02) 157-172
• 19 Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006; 26 (06) 565-574
• 20 Vickers AJ, Cronin AM, Elkin EB, Gonen M. Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med Inform Decis Mak 2008; 8: 53
• 21 Zhu WG, Xiong QM, Hong K. Meta-analysis of CHADS2 versus CHA2DS2-VASc for predicting stroke and thromboembolism in atrial fibrillation patients independent of anticoagulation. Texas Hear Inst J 2015; 42: 6-15
• 22 Olesen JB, Lip GYH, Hansen ML. et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ 2011; 342: d124
• 23 Chao TF, Liu CJ, Tuan TC. et al. Comparisons of CHADS2 and CHA2DS2-VASc scores for stroke risk stratification in atrial fibrillation: Which scoring system should be used for Asians?. Hear Rhythm 2016; 13: 46-53
• 24 Proietti M, Farcomeni A, Romiti GF. et al. Association between clinical risk scores and mortality in atrial fibrillation: systematic review and network meta-regression of 669,000 patients. Eur J Prev Cardiol 2020; 27 (06) 633-644
• 25 Bassand J-P, Accetta G, Camm AJ. et al; GARFIELD-AF Investigators. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J 2016; 37 (38) 2882-2889
• 26 Camm AJ, Accetta G, Ambrosio G. et al; GARFIELD-AF Investigators. Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation. Heart 2017; 103 (04) 307-314
• 27 Camelo-Castillo A, Rivera-Caravaca JM, Marín F, Vicente V, Lip GYH, Roldán V. Predicting adverse events beyond stroke and bleeding with the ABC-stroke and ABC-bleeding scores in patients with atrial fibrillation: the Murcia AF Project. Thromb Haemost 2020; 120 (08) 1200-1207
• 28 Esteve-Pastor MA, Roldán V, Rivera-Caravaca JM, Ramírez-Macías I, Lip GYH, Marín F. The use of biomarkers in clinical management guidelines: a critical appraisal. Thromb Haemost 2019; 119 (12) 1901-1919