Non-valvular atrial fibrillation patients with none or one additional risk factor of the CHA₂DS₂-VASc score

Summary

Oral anticoagulation (OAC) to prevent stroke has to be balanced against the potential harm of serious bleeding, especially intracranial haemorrhage (ICH). We determined the net clinical benefit (NCB) balancing effectiveness and safety of no antithrombotic therapy, aspirin and warfarin in AF patients with none or one stroke risk factor. Using Danish registries, we determined NCB using various definitions intrinsic to our cohort (Danish weights at 1 and 5 year follow-up), with risk weights which were derived from the hazard ratio (HR) of death following an event, relative to HR of death after ischaemic stroke. When aspirin was compared to no treatment, NCB was neutral or negative for both risk strata. For warfarin vs no treatment, NCB using Danish weights was neutral where no risk factors were present and using five years follow-up. For one stroke risk factor, NCB was positive for warfarin vs no treatment, for one year and five year follow-up. For warfarin vs aspirin use in patients with no risk factors, NCB was positive with one year follow-up, but neutral with five year follow-up. With one risk factor, NCB was generally positive for warfarin vs aspirin. In conclusion, we show a positive overall advantage (i.e. positive NCB) of effective stroke prevention with OAC, compared to no therapy or aspirin with one additional stroke risk factor, using Danish weights. ‘Low risk’ AF patients with no additional stroke risk factors (i.e. CHA2DS2-VASc 0 in males, 1 in females) do not derive any advantage (neutral or negative NCB) with aspirin, nor with warfarin therapy in the long run.

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

Keywords

Net clinical benefit - mortality - stroke - bleeding

• References

• 1 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.
• 2 Ruff CT, Giugliano RP, Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet 2014; 383: 955-962.
• 3 Camm A, Lip G, 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 Hear J 2012; 33: 2719-2747.
• 4 National-Institute-for-Health-and-Care-Excellence.. Atrial fibrillation: the management of atrial fibrillation. (Clinical guideline 180.) 2014 http://guidance.nice.org.uk/CG180 2014; http://guidance.nice.org.uk/CG180 Available at: http://guidance.nice.org.uk/CG180
• 5 Singer DE, Chang Y, Fang MC. et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med 2009; 151: 297-305.
• 6 Connolly SJ, Eikelboom JW, Ng J. et al. 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.
• 7 January CT, Wann LS, Alpert JS. et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. A Report of the 2014; 64: e1-e76.
• 8 Friberg L, Skeppholm M, Terént A. Benefit of Anticoagulation Unlikely in Patients With Atrial Fibrillation and a CHA2DS2-VASc Score of 1. J Am Coll Cardiol 2015; 65: 225-232.
• 9 Chao T-F, Liu C-J, Wang K-L. et al. Should Atrial Fibrillation Patients With 1 Additional Risk Factor of the CHA2DS2-VASc Score (Beyond Sex) Receive Oral Anticoagulation?. J Am Coll Cardiol 2015; 65: 635-642.
• 10 Lip GYH, Skjøth F, Rasmussen LH. et al. Oral Anticoagulation, Aspirin, or No Therapy in Patients With Nonvalvular AF With 0 or 1 Stroke Risk Factor Based on the CHA2DS2-VASc Score. J Am Coll Cardiol. 2015 Epub ahead of print.
• 11 Nielsen PB, Chao T. The risks of risk scores for stroke risk assessment in atrial fibrillation. Thromb Haemost 2015; 113: 1170-1173.
• 12 Olesen JB, Torp-Pedersen C. Stroke risk in atrial fibrillation: Do we anticoagulate CHADS2 or CHA2DS2-VASc1, or higher?. Thromb Haemost 2015; 113: 1165-1169.
• 13 Lip GYH, Skjøth F, Rasmussen LH. et al. Net Clinical Benefit for Oral Anticoagulation, Aspirin, or No Therapy in Nonvalvular Atrial Fibrillation Patients With One Additional Risk Factor of the CHA2DS2– VASc Score (Beyond Sex). J Am Coll Cardiol. 2015 Epub ahead of print.
• 14 Ray W. Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 2003; 158: 915-920.
• 15 Olesen JB, Lip GYH, Lindhardsen J. et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study. Thromb Haemost 2011; 106: 739-749.
• 16 Friberg L, Rosenqvist M, Lip GYH. Net clinical benefit of warfarin in patients with atrial fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012; 125: 2298-2307.
• 17 Nielsen PB, Skjøth F, Rasmussen LH. et al. Using the CHA2DS2-VASc score for stroke prevention in atrial fibrillation: A focus on vascular disease, females and simple practical application. Can J Cardiol. 2015 Epub ahead of print.
• 18 Friberg L, Rosenqvist M. Cardiovascular hospitalisation as a surrogate endpoint for mortality in studies of atrial fibrillation: Report from the Stockholm Cohort Study of Atrial Fibrillation. Europace 2011; 13: 626-633.
• 19 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.
• 20 Skjøth F, Larsen TB, Rasmussen LH. et al. Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation. An indirect comparison analysis. Thromb Haemost 2014; 111: 1-8.
• 21 Giugliano RP, Ruff CT, Braunwald E. et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2013; 369: 2093-2104.
• 22 Eckman MH, Singer DE, Rosand J. et al. Moving the tipping point: the decision to anticoagulate patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2011; 4: 14-21.
• 23 Lip GYH, Clemens A, Noack H. et al. Patient outcomes using the European label for dabigatran. A post-hoc analysis from the RE-LY database. Thromb Haemost 2014; 111: 933-942.
• 24 De Caterina R, Husted S, Wallentin L. et al. Vitamin K antagonists in heart disease: Current status and perspectives (Section III). Position Paper of the ESC Working Group on Thrombosis – Task Force on Anticoagulants in Heart Disease. Thromb Haemost 2013; 110: 1087-1107.
• 25 Lane DA, Lip GYH. Patient’s values and preferences for stroke prevention in atrial fibrillation: balancing stroke and bleeding risk with oral anticoagulation. Thromb. Haemost 2014; 111: 381-383.
• 26 Lahaye S, Regpala S, Lacombe S. et al. Evaluation of patients’ attitudes towards stroke prevention and bleeding risk in atrial fibrillation. Thromb Haemost 2013; 111.
• 27 Friberg L, Rosenqvist M, Lip GYH. Net clinical benefit of warfarin in patients with atrial fibrillation: A report from the swedish atrial fibrillation cohort study. Circulation 2012; 125: 2298-2307.
• 28 Olesen JB, Lip GYH, Lindhardsen J. et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study. Thromb Haemost 2011; 106: 739-749.
• 29 Rix TA, Riahi S, Overvad K. et al. Validity of the diagnoses atrial fibrillation and atrial flutter in a Danish patient registry. Scand Cardiovasc J 2012; 46: 149-153.