1. 1 Statin treatment is associated with improved prognosis in patients with AF-related stroke G. Ntaios, V. Papavasileiou, K.Makaritsis, A.Karagiannaki, H.Milionis, E.Manios, P. Michel, G.Y.H. Lipe, K. Vemmos G. Ntaios 1, V. Papavasileiou 1, K.Makaritsis 1, A.Karagiannaki 1, H.Milionis 2, E.Manios 3, P. Michel 4, G.Y.H. Lipe 5, K. Vemmos 3 1 Department of Medicine, University of Thessaly, Larissa, Greece 2 Department of Medicine, University of Ioannina, Ioannina, Greece 3 Department of Clinical Therapeutics, University of Athens, Athens, Greece 4 Acute Stroke Unit, CHUV, University of Lausanne, Lausanne, Switzerland 5 University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom

2. 2 Statin therapy in ischemic stroke patients of presumably atherosclerotic origin. (ACC/AHA guidelines) No recommendation for statin therapy in stroke patients of non- atherosclerotic origin, e.g. strokes related to atrial fibrillation (AF).

3. 3 Does statin treatment in patients with AF-related stroke affect on survival & risk for stroke recurrence & future cardiovascular events????

4. 4 Inclusion criteria Acute first-ever ischemic stroke AF-related stroke No history of coronary artery disease (CAD) No clinically manifest peripheral artery disease Athens Stroke Registry Between January 2000 and December 2011 not **Patients with transient ischaemic attack (TIA) or recurrent stroke not included in the analysis

5. 5 Methods 2 groups: -off-statin -on-statin at discharge follow-up: After 1, 3 & 6 months & yearly -Primary outcome: overall mortality -Secondary outcomes: stroke recurrence & a composite cardiovascular endpoint (recurrent stroke, myocardial infarction, aortic aneurysm rupture or sudden cardiac death)

6. 6 Results  Among 1602 stroke patients, 404 (25.2%) with AF-related stroke were included in the analysis.  102 of them (25.2%) were discharged on statin & 302 (74,8%) without statin.  92 cardiovascular events in 72 patients during a median follow-up of 22 months (Table 1).  Significant difference between the 2 groups in the rate of sudden cardiac death (2% in the on-statin group vs. 10.6% in the off-statin group).

7. 7 Results

8. Results  Statin treatment was independently associated with lower mortality during the median 22 months follow-up (Table 2).

9. 9 Results

10. Results  Significantly different cumulative probability of survival during the median 22 months between the 2 groups (Figure 1).

11. 11 Figure 1. Figure 1. Kaplan– Meier curves of the 5-years' cumulative probability of overall survival. Results

12. Results  Statin treatment was independently associated with a lower risk for the composite cardiovascular endpoint during the median 22 months follow-up (Table 2).

13. 13 Results

14. Results  Significantly different cumulative probability of new cardiovascular event between the on-statin & off-statin group (Figure 2).

15. 15 Figure 2. Figure 2. Kaplan–Meier curves of the 5-years' cumulative probability of new cardiovascular event. Results

16. Results not  Statin treatment was not associated with stroke recurrence during the median 22 months follow-up, despite a strong trend in favor of the on- statin group (Table 2).

17. 17 Results

18. Results  Difference of borderline statistical significance in the cumulative probability of stroke recurrence between the on-statin & the off-statin group (Figure 3).

19. 19 Results Figure 3. Figure 3. Kaplan–Meier curves of the 5-years' cumulative probability of stroke recurrence

20. 20 Discussion  Association of statin treatment with improved survival & reduced risk for future cardiovascular events, in these patients with AF-related stroke.  No  No significant difference between on-statin & offstatin groups with regards to the endpoint of stroke recurrence. not  The beneficial effect of statins in patients with AF-related stroke was driven by the reduction of cardiovascular not cerebrovascular events.

21. 21 Discussion  Although there is no specific recommendation about patients with AF-related stroke, many clinicians start statin. confirmation  This needs confirmation in a randomized trial setting.  Similar findings in an analysis of a Korean stroke registry.

22. 22 Main strengths of study  Assessment of mortality, stroke recurrence & cardiovascular events and the median follow-up period of 22 months in a consecutive series of stroke patients. not  Analysis not restricted to dyslipidemic patients.  All  All patients were included* irrespective of their baseline LDL levels. * patients with AFrelated stroke is a high-risk group for stroke recurrence & future cardiovascular events and cardiovascular & overall mortality

23. 23 Limitations  Collection & entry bias  Residual confounding not  Adherence to statin treatment not assessed not  Efficiency of anticoagulation not available (the time within therapeutic range (TTR), for patients receiving vitamin-K antagonists)

24. 24 Summary Statin treatment in patients with AF-related stroke was associated with improved survival & reduced risk for future cardiovascular events in this long-term registry. cardiovascular The beneficial effect of statins in patients with AF-related stroke was driven by the reduction of cardiovascular rather than cerebrovascular events. Further confirmation is urgently warranted in a randomized trial setting, given the high incidence of AF-related stroke & its poor prognosis.

25. 25

26. 26 Thank you for your attention