Left Ventricular Systolic Dysfunction, Heart Failure and the Risk of Stroke and Systemic Embolism in Patients with Atrial Fibrillation: Insights from the ARISTOTLE Trial.

McMurray JJ, Ezekowitz JA, Lewis BS, et al; for the ARISTOTLE Committee and Investigators
Circ Heart Fail. 2013 Apr 10. [Epub]

Background

One of the most commonly used tools to estimate the risk of stroke in patients with atrial fibrillation
is the Cardiac failure, Hypertension, Age, Diabetes, Stroke (doubled) [CHADS2] score [1]. Although CHADS2 and other scores include “cardiac failure” or “congestive heart failure”, it is unclear how heart failure should be defined and whether it is an independent risk factor for thromboembolism [2-7].
A retrospective analysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE) trial was performed to further examine the relationship between ventricular function, clinical heart failure and the risk of stroke or systemic embolism in patients with atrial fibrillation [8,9]. The effect of apixaban, compared with warfarin, according to left ventricular function and heart failure status was also examined.
The risk of a number of outcomes including the composite of SSE or death (to take account of competing risks) and composite of stroke or systemic embolism (SSE), major bleeding or death ("net clinical benefit") were calculated in 3 patient groups: 1) No HF/no LVSD (n=8728) 2) HF/no  LVSD (n=3207) and 3) LVSD with/without symptomatic HF (n=2736).

Main results

• The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding or death  10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24) and lowest in patients without HF or LVSD (1.54; 5.27); each comparison p<0.0001.
• Each outcome was less frequent in patients treated with apixaban: in the whole ARISTOTLE population, the apixaban/warfarin hazard ratio for SSE or death 0.89 (95% CI 0.81,0.98) p=0.02; for SSE, major bleed or death it was 0.85 (0.78,0.92); p<0.001.
• Compared with warfarin, apixaban had no effect on heart failure hospitalization.
• There was no heterogeneity of treatment-effect across the 3 groups.

Conclusion

Anticoagulated patients with atrial fibrillation and LVSD and those with atrial fibrillation and HF-PEF had a numerically higher adjusted risk of SSE than patients with neither LVSD nor HF, although the difference between the patient groups was not significant. Similarly, there was no relationship between risk of SSE and EF considered as a continuous measure. Apixaban was superior to warfarin with respect to both efficacy and safety outcomes in all patient groups, with the greatest absolute benefit in the highest risk patients with LVSD.

References

1. European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010; 31: 2369-429.
2. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007; 69: 546-54.
3. Stroke Risk in Atrial Fibrillation Working Group. Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation. Stroke. 2008;39: 1901-10.
4. Lip GY, Halperin JL. Improving stroke risk stratification in atrial fibrillation. Am J Med. 2010; 123: 484-8.
5. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012; 33: 1500-10.
6. Olesen JB, Lip GY, 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.
7. No authors listed. Predictors of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators. Ann Intern Med. 1992; 116: 6-12.
8. Lopes RD, Alexander JH, Al-Khatib SM, et al; ARISTOTLE Investigators. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010; 159: 331-9.
9. 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: 981-92.

Find this article online