Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS₂ score=1

Summary

In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS₂ score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.5%) had a CHADS₂ score of 1 and were liable to treatment with an antiplatelet agent or an anticoagulant. An oral anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793 days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%) were recorded. The administration of an anticoagulant was associated with a lower rate of events (relative risk=0.42, 95% confidence interval 0.29–0.60, p<0.0001) than when no anticoagulant was prescribed. Results remained similar after adjustment for age and other confounding factors. In contrast, prescription of an antiplatelet agent was not associated with a lower risk of events. Factors independently associated with an increased risk of events were older age (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus, prescription of an anticoagulant is independently associated with a decreased risk of death or stroke among patients with AF and a CHADS₂ score =1.

Keywords

Atrial fibrillation - antithrombotic treatment - oral anticoagulant - anti-platelet agent

• References

• 1 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke 1991; 22: 983-988.
• 2 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.
• 3 Levine MN, Hirsh J, Landefeld S, Raskob G. Hemorrhagic complications of anticoagulant treatment. Chest 1992; 102 (Suppl. 04) 352S-363S.
• 4 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.
• 5 Fuster V, Rydén LE, Cannom DS. et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Eur Heart J 2006; 27: 1979-2030.
• 6 Singer DE, Albers GW, Dalen JE. et al. American College of Chest Physicians. Anti-thrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133 (Suppl. 06) 546S-592S.
• 7 Nieuwlaat R, Olsson SB, Lip GY. et al. Guideline-adherent antithrombotic treatment is associated with improved outcomes compared with undertreatment in high-risk patients with atrial fibrillation. The Euro Heart Survey on Atrial Fibrillation. Am Heart J 2007; 153: 1006-1012.
• 8 Healey JS, Hart RG, Pogue J. et al. Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin in patients with atrial fibrillation according to stroke risk: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE-W). Stroke 2008; 39: 1482-1486.
• 9 Connolly SJ, Pogue J, Hart RG. et al. ACTIVE Investigators. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009; 360: 2066-2078.
• 10 Hart RG, Pearce LA, McBride R. et al. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 1999; 30: 1223-1229.
• 11 Mant J, Hobbs FD, Fletcher K. et al. BAFTA investigators; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493-503.
• 12 Rash A, Downes T, Portner R. et al. A randomised controlled trial of warfarin versus aspirin for stroke prevention in octogenarians with atrial fibrillation (WASPO). Age Ageing 2007; 36: 151-156.
• 13 Nieuwlaat R, Dinh T, Olsson SB. et al. Should we abandon the common practice of withholding oral anticoagulation in paroxysmal atrial fibrillation?. Eur Heart J 2008; 29: 915-922.
• 14 Flaker GC, Gruber M, Connolly SJ. et al. Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials. Halperin JL; SPORTIF Investigators. Am Heart J 2006; 152: 967-973.
• 15 Lip GY. Don’t add aspirin for associated stable vascular disease in a patient with atrial fibrillation receiving anticoagulation. Br Med J 2008; 336: 614-615.
• 16 Rubboli A, Halperin JL. Pro: ‘Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regime in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions‘. Thromb Haemost 2008; 100: 752-753.
• 17 Roldán V, Marín F. Contra: ‘Antithrombotic therapy with warfarin, aspirin and clopidogrel is the recommended regimen in anticoagulated patients who present with an acute coronary syndrome and/or undergo percutaneous coronary interventions‘. Not for everybody. Thromb Haemost 2008; 100: 754-755.
• 18 Chobanian AV, Bakris GL, Black HR. et al. The seventh report of the Joint National Committee on the prevention, detection, evaluation and treatment of high blood pressure. The JNC 7 Report. J Am Med Assoc 2003; 289: 2560-2572.
• 19 Senn S, Graf E, Caputo A. Stratification for the propensity score compared with linear regression techniques to assess the effect of treatment or exposure. Stat Med 2007; 26: 5529-5544.