Thromb Haemost 2014; 111(03): 549-556
DOI: 10.1160/TH13-12-1033
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Composite risk scores and composite endpoints in the risk prediction of outcomes in anticoagulated patients with atrial fibrillation

The Loire Valley Atrial Fibrillation Project
Amitava Banerjee
1   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
,
Laurent Fauchier
2   Service de Cardiologie, Pôle Coeur Thorax Vasculaire, Centre Hospitalier, Universitaire Trousseau et Faculté de Médecine, Université François Rabelais, Tours, France
,
Anne Bernard-Brunet
2   Service de Cardiologie, Pôle Coeur Thorax Vasculaire, Centre Hospitalier, Universitaire Trousseau et Faculté de Médecine, Université François Rabelais, Tours, France
,
Nicolas Clementy
2   Service de Cardiologie, Pôle Coeur Thorax Vasculaire, Centre Hospitalier, Universitaire Trousseau et Faculté de Médecine, Université François Rabelais, Tours, France
,
Gregory Y. H. Lip
1   University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
› Author Affiliations
Further Information

Publication History

Received: 19 December 2013

Accepted after major revision: 19 January 2014

Publication Date:
22 November 2017 (online)

Summary

Several validated risk stratification schemes for prediction of ischaemic stroke (IS)/thromboembolism (TE) and major bleeding are available for patients with non-valvular atrial fibrillation (NVAF). On the basis for multiple common risk factors for IS/TE and bleeding, it has been suggested that composite risk prediction scores may be more practical and user-friendly than separate scores for bleeding and IS/TE. In a long-term prospective hospital registry of anticoagulated patients with newly diagnosed AF, we compared the predictive value of existing risk prediction scores as well as composite risk scores, and also compared these risk scoring systems using composite endpoints. Endpoint 1 was the simple composite of IS and major bleeds. Endpoint 2 was based on a composite of IS plus intracerebral haemorrhage (ICH). Endpoint 3 was based on weighted coefficients for IS/TE and ICH. Endpoint 4 was a composite of stroke, cardiovascular death, TE and major bleeding. The incremental predictive value of these scores over CHADS2 (as reference) for composite endpoints was assessed using c-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Of 8,962 eligible individuals, 3,607 (40.2%) had NVAF and were on OAC at baseline. There were no statistically significant differences between the c-statistics of the various risk scores, compared with the CHADS2 score, regardless of the endpoint. For the various risk scores and various endpoints, NRI and IDI did not show significant improvement (≥1%), compared with the CHADS2 score. In conclusion, composite risk scores did not significantly improve risk prediction of endpoints in patients with NVAF, regardless of how endpoints were defined. This would support individualised prediction of IS/TE and bleeding separately using different separate risk prediction tools, and not the use of composite scores or endpoints for everyday ‘real world’ clinical practice, to guide decisions on thromboprophylaxis.

Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.

 
  • References

  • 1 Lloyd-Jones DM, Wang TJ, Leip EP. et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 2004; 110: 1042-1046.
  • 2 Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol 2011; 8: 30-41.
  • 3 Potpara TS, Stankovic GR, Beleslin BD. et al. A 12-year follow-up study of patients with newly-diagnosed lone atrial fibrillation: Implications of arrhythmia progression on prognosis: The Belgrade Atrial Fibrillation Study. Chest 2012; 14: 339-347.
  • 4 Conen D, Chae CU, Glynn RJ. et al. Risk of death and cardiovascular events in initially healthy women with new-onset atrial fibrillation. J Am Med Assoc 2011; 305: 2080-2087.
  • 5 Frost L, Vestergaard P, Mosekilde L. et al. Trends in incidence and mortality in the hospital diagnosis of atrial fibrillation or flutter in Denmark, 1980-1999. Int J Cardiol 2005; 103: 78-84.
  • 6 Heeringa J, van der Kuip DA, Hofman A. et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam Study. Eur Heart J 2006; 27: 949-953.
  • 7 Potpara TS, Lip GY, Apostolakis S. New anticoagulant treatments to protect against stroke in atrial fibrillation. Heart 2012; 98: 1341-1347.
  • 8 Connolly SJ, Ezekowitz MD, Yusuf S. et al. RE-LY Steering Committee and Investigators.. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
  • 9 Patel MR, Mahaffey KW, Garg J. et al. ROCKET AF Investigators.. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
  • 10 Granger CB, Alexander JH, McMurray JJ. et al. ARISTOTLE Committees and Investigators.. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992.
  • 11 Gage BF, Waterman AD, Shannon W. et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
  • 12 Lip GY, Nieuwlaat R, Pisters R. et al. 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: 263-272.
  • 13 Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for is-chaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33: 1500-1510.
  • 14 Pisters R, Lane DA, Nieuwlaat R. et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138: 1093-1100.
  • 15 Gage BF, Yan Y, Milligan PE. et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-719.
  • 16 Camm AJ, Lip GY, De Caterina R. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747.
  • 17 Gallego P, Roldán V, Torregrosa JM. et al. Relation of the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and mortality in anticoagu-lated patients with atrial fibrillation. Circ Arrhythm Electrophysiol 2012; 5: 312-318.
  • 18 Lip GY, Andreotti F, Fauchier L. et al. European Heart Rhythm Association.. Bleeding risk assessment and management in atrial fibrillation patients. Executive Summary of a Position Document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. Thromb Haemost 2011; 106: 997-1011.
  • 19 Singer DE, Chang Y, Fang MC. et al. The net clinical benefit of warfarin antico-agulation in atrial fibrillation. Ann Intern Med 2009; 151: 297-305.
  • 20 Hohnloser SH, Oldgren J, Yang S. et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation 2012; 125: 669-676.
  • 21 Connolly SJ, Eikelboom JW, Ng J. et al. ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) Steering Committee and Investigators.. Net clinical benefit of adding clopidogrel to aspirin therapy in patients with atrial fibrillation for whom vitamin K antagonists are unsuitable. Ann Intern Med 2011; 155: 579-586.
  • 22 Banerjee A, Fauchier L, Vourc’h P. et al. Renal impairment and ischaemic stroke risk assessment in patients with atrial fibrillation: The Loire Valley Atrial Fibrillation Project. J Am Coll Cardiol 2013; 61: 2079-2087.
  • 23 Pencina MJ, D’Agostino Sr. RB, DAgostino Jr. RB. et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassifi-cation and beyond. Stat Med 2008; 27: 157-172.
  • 24 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: 837-845.
  • 25 Lip GY, Lane DA, Buller H. et al. Development of a Novel Composite Stroke and Bleeding Risk Score in Patients With Atrial Fibrillation: The AMADEUS Study. Chest 2013; 144: 1839-1847.
  • 26 Banerjee A, Lane DA, Torp-Pedersen C. et al. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107: 584-589.
  • 27 Bonati LH, Ederle J, McCabe DJ. et al. CAVATAS Investigators.. Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial. Lancet Neurol 2009; 8: 908-917.
  • 28 MacKay-Lyons M, Gubitz G, Giacomantonio N. et al. Program of rehabilitative exercise and education to avert vascular events after non-disabling stroke or transient ischemic attack (PREVENT Trial): a multi-centred, randomised controlled trial. BMC Neurol 2010; 10: 122.
  • 29 Diener HC, Sacco R, Yusuf S. Steering Committee; PRoFESS Study Group.. Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS). Cerebrovasc Dis 2007; 23: 368-380.