Anti-thromboticthrombotic drugs

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1 Atrial Fibrillation 2011: Anticoagulation strategies and clinical outcomes Panos E. Vardas President Elect of the ESC, Prof. of Cardiology, University Hospital of Crete

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3 Clinical outcomes affected by AF

4 Pharmacological options for AF in 2011 Anti-arrhythmic drugs Rate control drugs Drugs with no specific anti-arrhythmic arrhythmic actions Anti-thromboticthrombotic drugs

5 Antithrombotic Treatment New ESC guidelines The most important addition regarding antithrombotic treatment is the recommendation to use the CHA2DS2-VASc scoring system in patients with achads2 score of 0-1. Specifically, the CHADS2 stroke risk stratification scheme is recommended as a simple means of assessing stroke risk, particularly suited to primary care doctors and non-specialists specialists. In patients with a CHADS2 score of 2, chronic OAC therapy is recommended, d unless contraindicated. Where amore detailed stroke risk assessment is indicated, it is recommended to use the CHA2DS DS2-VASc score.

6 New risk stratification scheme CHADS 2 CHA 2 DS 2-VAS C Congestive Heart Failure 1 Hypertension 1 Age > 75 years 1 Diabetes Mellitus 1 Prior Stroke or TIA 2 Age gradation and vascular disease are parts of the risk score

7 Approach to thromboprophylaxis in patients with AF

8 Approach to thromboprophylaxis in patients with AF

9 Bleeding Risk Assessment New ESC guidelines The Guidelines also highlight the importance of bleeding risk assessment prior to the initiation of anticoagulation. For this reason the HAS-BLED bleeding risk score is recommended and a score of 3 is considered indicative of high risk, patients who require caution and regular review following the initiation of antithrombotic therapy.

10 HAS-BLED bleeding risk score

11 New approach to thromboprophylaxis in patients with AF New OAC drugs, which may be viable alternatives to a VKA, may ultimately be considered. For example, should both doses of dabigatran or rivaroxaban receive regulatory approval for stroke prevention in AF, dabigatran may be considered, as an alternative to adjusted dose VKA therapy.

12 RE-LY STUDY DESIGN INR = International normalized ratio. Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada. Connolly SJ, et al. N Engl J Med 2009; 361: Ezekowitz MD, et al. Am Heart J 2009;157:

13 RE-LY BASELINE CHARACTERISTICS CHF = congestive heart failure; MI = myocardial infarction; TIA = transient ischaemic attack; VKA = vitamin K antagonist. Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada. Connolly SJ, et al. N Engl J Med 2009;361:

14 RE-LY STROKE OR SYSTEMIC EMBOLISM (SSE) Non-inferiority P value Superiority P value Dabigatran 110 mg BID vs. warfarin Ma argin=1.46 < Dabigatran 150 mg BID vs. warfarin <0.001 < Hazard ratio Error bars = 95% CI; BID = twice daily. Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada. Connolly SJ, et al. N Engl J Med 2010;363:

15 RE-LY TIME TO FIRST STROKE OR SSE RR = relative risk; RRR = relative risk reduction; SSE = systemic embolism. Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada. Connolly SJ, et al. N Engl J Med 2010;363:

16 RE-LY RATEOFSTROKEORSSE OR SSE D = dabigatran; RR = relative risk; RRR = relative risk reduction; SSE = systemic embolism. Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada. Connolly SJ, et al. N Engl J Med 2010;363:

17 RE-LY HAEMORRHAGIC STROKE D = dabigatran; RR = relative risk; RRR = relative risk reduction. Dabigatran etexilate is not approved for clinical use in stroke prevention in atrial fibrillation outside the US and Canada. Connolly SJ, et al. N Engl J Med 2009;361:

18 ROCKET-AF was powered for non-inferiority of rivaroxaban vs. warfarin for the primary endpoint Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

19 ROCKET-AF: baseline characteristics (I) Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

20 ROCKET-AF: study conduct Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

21 ROCKET-AF: stroke and non-cns embolism non-inferiority analysis Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

22 ROCKET-AF: stroke and non-cns embolism superiority analysis HR = hazard ratio; ITT = intention-to-treat Event rates per 100 patient-years; error bars = 95% confidence intervals Based on safety on-treatment or ITT through site notification populations Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

23 ROCKET-AF: secondary efficacy outcomes (I) Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

24 ROCKET-AF: secondary efficacy outcomes (II) Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

25 ROCKET-AF: primary safety outcomes (I) Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

26 ROCKET-AF: conclusions Rivaroxaban has been shown to be non-inferior to warfarin for the prevention of stroke and non-cns embolism Rivaroxaban failed to show superiority over warfarin for the primary endpoint in the ITT analysis Only demonstrated superiority in the on-treatment population Similar rates of ischaemic stroke observed with rivaroxaban and warfarin in both ITT and on-treatment population analyses Rivaroxaban significantly reduced the risk of haemorrhagic stroke compared with warfarin in the ITT analysis Comparable rates of bleeding with bleeding in both treatment populations reduced intracranial Firm conclusions can only be made once the full publication is available Disclaimer: Rivaroxaban is not approved for clinical use in stroke prevention in atrial fibrillation. This information is provided for medical education purposes only. Mahaffey KW et al. Presented at AHA 2010; Session LBCT ; Available at:

27 Is there a role for dual antiplatelet therapy? In patients who refuse euse or have clear cea contraindication to take OAC and who are at high risk of stroke, the combination of aspirin 100 mg and clopidogrel 75 mg can be used, with an increased risk of hemorrhagic events (Class IIa, LOE B) Connoly SJ et al, Active Study, NEJM 2009;360

28 Antithrombotic therapy in 2011 Conclusions Vitamin K antagonists remain the gold standard of anti-thromboticthrombotic therapy in AF New tools have been established in the new ESC AF guidelines to estimate stroke (CHA 2 DS 2 VASc) and hemorrhage (HASBLED) risk Dabigadran (a direct thrombin inhibitor) and rivaroxaban (a direct Xa-factor inhibitor) have been proved to be equally effective to vitamin-k antagonists. However they have not been approved yet for stroke prevention in Europe.