How to manage a patient who needs thrombolysis in acute stroke, ablation or angioplasty/stenting? Janet M McComb Freeman Hospital Newcastle upon Tyne

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1 How to manage a patient who needs thrombolysis in acute stroke, ablation or angioplasty/stenting? Janet M McComb Freeman Hospital Newcastle upon Tyne

2 What do the guidelines say? What happens with warfarin in this condition? How do the novel anticoagulants compare with warfarin in this condition?

3 Stroke Alteplase is recommended for the treatment of acute ischaemic stroke ASA 300mg should be given

4 Stroke

5 Stroke Class IA indication Intravenous rtpa, 0.9mg/kg is recommended for selected patients who may be treated within 3 hours of the onset of ischemic stroke Adams et al Stroke 2007;38:

6 Stroke Characteristics of patients with ischemic stroke who could be treated with rtpa Not taking an oral anticoagulant, or if anticoagulant being taken, INR 1.7 If receiving heparin in previous 48 hours, aptt must be in the normal range Adams et al Stroke 2007;38:

7 Stroke Class IB indication rtpa should be administered to eligible patients who can be treated in the time period of hours after stroke All patients receiving an oral anticoagulant are excluded regardless of the INR Del Zoppo et al Stroke 2009;40:

8 Stroke 107 consecutive patients with acute ischaemic stroke treated with tpa 13 taking warfarin at baseline, median INR 1.21 ( ) no warfarin warfarin OR 13.5 [ ] INR age AF sich Prabhakaran et al Arch Neurol 2010;67:

9 Stroke GWTG stroke registry 1802 payients with acute ischaemic stroke treated with tpa & taking warfarin at baseline, median INR 1.20 ( ) no warfarin 4.6 sich warfarin 7.7 OR 1.1 [ ], p= Xian et al JAMA 2012;107:

10 Stroke 39 mice pretreated with dabigatran (75 or mg/kg), or warfarin 2mg/Kg or saline, 3 hours RMCA occlusion, then treated with rtpa before reperfusion Pfeilschifter et al Ann Neurol 2012;71:

11 Stroke 5 case reports in man 4 successful reperfusion, 1 fatal haemorrhage Currently, thrombolysis is contraindicated in patients with acute ischaemic stroke already taking novel anticoagulants

12 Ablation Anticoagulation guidelines that pertain to cardioversion of AF to be adhered to in patients who present for an AF ablation in AF Calkins et al Heart Rhythm 2012;9:

13 Ablation Clinical experience with these new anticoagulation agents in association with an AF ablation procedure at the present time is limited Calkins et al Heart Rhythm 2012;9:

14 Ablation 123 consecutive patients Dabigatran started 22 hours after RFA 27.6% on dabigatran pre RFA stopped it 36 hours pre No embolic phenomena in any patient post RFA 67.6 Winkle et al J Cardiovasc Electrophysiol 2012;23: consecutive patients Dabigatran started 22 hours after RFA 19.8% on dabigatran pre RFA No major bleeding in any patient post RFA Snipelisky et al J Inter Card Electrophysiol 2012;35:29-33

15 Ablation Prospective multicentre registry Dabigatran until the night before, or uninterrupted warfarin Dabigatran OR 2.76 [ ] dabigatran warfarin thromboembolism major bleeding total bleeding composite Lakkireddy et al J Am Coll Cardiol 2012;59:

16 Ablation Consecutive series, 211 patients Dabigatran (110mg bd) until the night before, in 110, or uninterrupted warfarin in 101 Thromboembolism None in either group 67.6 (silent cerebral lesions in 3.3% of a subgroup who underwent imaging) 80.6 Bleeding dabigatran warfarin tamponade minor bleeding total bleeding Kaseno et al Circulation Journal 2012 advance publication

17 Ablation Currently, the limited evidence available suggests that using novel anticoagulants before and after ablation is eqivalent to warfarin during ablation, is associated with excess bleeding risk, compared with warfain

18 Acute coronary syndrome Lip et al European Heart Journal 2010; 31:

19 ACS PCI & stenting Haemorrhagic risk Low or intermediate High Type of stent Bare metal or drug eluting Bare metal Recommendation Drug Dose/day duration ASA 100 mg clopidogrel 75 mg 6 months* warfarin INR ASA 100 mg 4 weeks* clopidogrel 75mg warfarin INR *Up to 12 months warfarin + clopidogrel/or aspirin Life long warfarin Lip et al European Heart Journal 2010; 31:

20 Acute coronary syndrome Benefit MI RR 0.56 [ ] Meta analysis, 5938 patients Rothberg et al Ann Intern Med 2005;143:

21 Acute coronary syndrome Risk of bleeding RR 2.5[ ] Meta analysis, 5938 patients Rothberg et al Ann Intern Med 2005;143:

22 Acute coronary syndrome RIVAROXIBAN ATLAS ACS-TIMI patients stabilised after ACS randomised to rivaroxaban or placebo Death/MI/stroke/revasacularisation Significant bleeding HR 0.79[ ] p = 0.10 placebo rivaroxaban Mega et al Lancet 2009;374:29-38

23 Acute coronary syndrome RIVAROXIBAN ATLAS ACS 2-TIMI patients with recent ACS randomised to rivaroxaban or placebo HR 0.79[ ], p =0.10 HR 0.84[ ] p =0.008 Mega et al New Engl J Med 2012;366:9-19

24 Acute coronary syndrome RIVAROXIBAN placebo 10 rivaroxiban ATLAS ACS 2-TIMI patients with recent ACS randomised to rivaroxaban or placebo Death/MI/stroke major bleeding minor bleeding all bleeding ICH fatal bleeding Mega et al New Engl J Med 2012;366:9-19

25 Acute coronary syndrome APIXABAN APPRAISE 1715 patients with STEMI or ACS randomised to apixaban or placebo Significant bleeding Death/MI/stroke/ revasacularisation APPRAISE Steering Committee and Investigators Circulation 2009;119:

26 Acute coronary syndrome APIXABAN APPRAISE APPRAISE Steering Committee and Investigators Circulation 2009;119:

27 Acute coronary syndrome APIXABAN APPRAISE patients with STEMI or ACS randomised to apixaban or placebo CV death/mi/stroke HR 0.95[ ] p=0.51 Alexander et al New Engl J Med 2011;365:

28 Acute coronary syndrome APIXABAN APPRAISE patients with HR 2.59[ ] p=0.001 STEMI or ACS randomised to apixaban or placebo CV death/mi/stroke Alexander et al New Engl J Med 2011;365:

29 Acute coronary syndrome DABIGATRAN Meta analysis patients OR 1.33[ ] p=0.03 Uchino & Hernandez Arch Int Med 2012;172:

30 Acute coronary syndrome DABIGATRAN RE-DEEM 1861 patients with STEMI or ACS randomised to dabigatran or placebo Significant bleeding incidence HR placebo 50mg bd 75mg bd 110mg bd 150mg bd Oldgren et al Eur Heart J 2011;32:

31 Acute coronary syndrome Currently, the evidence available suggests that using novel anticoagulants in ACS patients more than doubles the risk of bleeding (as does warfarin) Rivaroxaban may improve coronary outcome, dabigatran may be deleterious

32 Conclusions The evidence is extremely limited in quantity, and much is observational (stroke & RFA) Novel anticoagulants increase bleeding risk, as does warfarin rtpa is contraindicated in acute ischaemic stroke in patients on warfarin or novel agents Novel agents used during RFA may increase bleeding risk Warfarin appears to have a higher benefit in ACS, than do novel agents, with the same risk