1 / 18

Preventing a Second Stroke

Preventing a Second Stroke. John Camm St. George’s University of London, UK. Declaration of Interest.

rafer
Download Presentation

Preventing a Second Stroke

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Preventing a Second Stroke John Camm St. George’s University of London, UK

  2. Declaration of Interest Chairman: ESC Guidelines on Atrial Fibrillation 2012 and Update 2012, ACC/AHA/ESC Guidelines on VAs and SCD; 2012 NICE Guidelines on ACS and NSTEMI; 2008 NICE Guidelines on heart failure; 2006 NICE Guidelines on Atrial Fibrillation Steering Committees:multiple trials including novel anticoagulants DSMBs:multiple trials including novel oral anticoagulants in AF Events Committees:one trial of novel oral anticoagulants and multiple trials of miscellaneous agents with CV adverse effects Consultant/Advisor/Speaker: Astra Zeneca, ChanRX, Gilead, Merck, Menarini, Otsuka, Sanofi, Servier, Xention, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Actelion, GlaxoSmithKline, InfoBionic, Incarda, Johnson and Johnson, Mitsubishi, Novartis, Takeda

  3. Questions to be Asked • About the first stroke • Was it ischaemic or haemorrhagic? • Was the patient anticoagulated? • Was the anticoagulation known to be adequate? • About the patient • Is atrial fibrillation present (or was it present)? • What is the thromboembolic risk (CHA2DS2-VASc)? • What is the bleeding risk?

  4. Questions to be Asked • About the first stroke • It was ischaemic • The patient was not anticoagulated • Was the anticoagulation known to be adequate? • About the patient • Atrial fibrillation is, or was, present • The thromboembolic risk was moderate to high • The bleeding risk was moderate Anticoagulate the patient with a NOAC

  5. Questions to be Asked • About the first stroke • It was haemorrhagic • The patient was anticoagulated • The anticoagulation status was unknown or high • About the patient • Atrial fibrillation is or was present • The thromboembolic risk was moderate or high • The bleeding is very high Consider device based anti-thrombotic strategy

  6. NOAC 4-trial Meta-analysis Full Dose Pre-specified meta-analysis of all 71,683 patients <0.0001 0.06 0.81 0.86 Ruff C, et al. Lancet 2013 0.5 1 Favours DOAC * Edoxaban is not approved for clinical use in AF 0.5 1 Favours DOAC

  7. Efficacy vs SafetyNOAC 4-trial Meta-analysis Full Dose 0.25 1 2 Favours NOAC * Edoxaban is not approved for clinical use in AF Ruff C, et al. Lancet 2013

  8. Ischaemic Stroke: Novel Agents vs Warfarin 0.5 1 1.5 *Ischaemic or uncertain type of stroke Favours NOACs Favours warfarin 1. Connolly SJ et al. N Engl J Med 2009;361:1139–51; 2. Connolly SJ et al. N Engl J Med 2010;363:1875–1876; 3. Patel MR et al. NEJM 2011;365:883–91 and Supplementary Appendix; 4. Granger et al. N Eng J Med 2011;365:981-92.

  9. ROCKET AFSubanalysis 20 prevention – Results Kaplan-Meier survival curve: Primary efficacy endpoint (stroke or systemic embolism) Prior stroke/TIA, warfarin No prior stroke/TIA, warfarin 7,468 (52%) patients had a previous stroke (n=4,907; 65%) or TIA (n=2,561; 34%) Prior stroke/TIA, rivaroxaban 7 No prior stroke/TIA, rivaroxaban 6 5 • HR: 0.94 (0.77 – 1.16) 4 Cumulative event rate - stroke/SE (%) 3 2 • HR: 0.77 (0.58 – 1.01) 1 0 0 6 12 18 24 30 Months from randomisation Intention-to-treat population Hankey GJ et al. Lancet Neurol 2012;11(4): 315–22

  10. ARISTOTLE:20Stroke Prevention - Results Apixaban vs. warfarin: • Previous stroke or TIA: HR:0.76; 95% CI: 0.56 to 1.03 • No previous stroke or TIA: HR: 0.82; 95% CI: 0.65 to 1.03 10 8 Previous stroke or TIA, warfarin (n=1742) 6 Previous stroke or TIA, apixaban (n=1694) Probability (%) 4 No previous stroke or TIA, warfarin (n=7339) 2 No previous stroke or TIA, apixaban (n=7426) 0 0 10 12 18 24 30 Time since randomisation (months) Easton et al. Lancet Neurol 2012;11:503–11

  11. ARISTOTLE: Major Bleeding - 10 and 20 Prevention Apixaban vs. warfarin: • Previous stroke or TIA: HR:0.73; 95% CI: 0.55 to 0.98 • No previous stroke or TIA: HR: 0.68; 95% CI: 0.58 to 0.80 10 Previous stroke or TIA, warfarin (n=1735) 8 No previous stroke or TIA, warfarin (n=7371) 6 Previous stroke or TIA, apixaban (n=1687) Probability (%) No previous stroke or TIA, apixaban (n=7401) 4 2 NNT to avoid one major bleed: – No previous stroke or TIA: 65 – Previous stroke or TIA: 54 0 0 10 12 18 24 30 Time since first dose of study drug (months) Easton et al. Lancet Neurol2012;11:503–11.

  12. Comparisons between NOACsDirect methodology

  13. Comparisons between NOACsIndirect methodology Rasmussen LH, et al BMJ 2012;345:e7097

  14. AHA/ASA 2012 Update SPAF and OAC Warfarin (Class I; Level of Evidence A), dabigatran (Class I; Level of Evidence B), apixaban (Class I; Level of Evidence B), and rivaroxaban (Class IIa; Level of Evidence B) • are all indicated for the prevention of first and recurrent stroke in patients with nonvalvular AF • The selection of an antithrombotic agent should be individualized on the basis of risk factors, cost, tolerability, patient preference, potential for drug interactions, and other clinical characteristics, including time in INR therapeutic range if the patient has been taking warfarin. Furie KL, et al. Stroke 2012 Dec;43(12):3442-53

  15. 20 Stroke PreventionGuidelines • 2012 German Guidelines on secondary stroke prevention recommend: • In patients with TIA or ischemic stroke and atrial fibrillation oral anticoagulation is recommended(Level of evidence Ib, strength of recommendation A) • Patients with ischemic stroke or TIA and atrial fibrillation should be treated with new anticoagulants (Level of evidence Ib, strength of recommendation B) • Apixaban is superior to aspirin (50–328 mg) in the prevention of recurrent stroke in patients with ischemic stroke or TIA and atrial fibrillation. Apixaban has a comparable bleeding risk as aspirin. Aspirin should no longer be used in secondary stroke prevention in patients with atrial fibrillation (Level of Evidence Ib, strength of recommendation B) Endres M, et al. 2012

  16. PROTECT-AF: Final Results 463 patients received Watchman and 244 warfarin Average CHADS2 scores 2.2 and 2.3, respectively Mean follow-up:45 months • Rate Ratios (95% CI) for Primary Efficacy and Safety End Points and Secondary End Points in PROTECT-AF, by Intention to Treat Reddy VY, et al. Abstract HRS Denver 2013

  17. Left Atria Appendage OcclusionPotential Indications • Ischaemic stroke despite adequate anticoagulation • High thromboembolic risk but previous intra-cerebral bleed on anticoagulants • High thrombo-embolic risk but previous life-threatening bleed on anticoagulants at correct INR • High thrombo-embolic risk but previous major bleed on anticoagulants • High thromboembolic risk (CHA2DS2VASc ≥ 2) with major risk of bleeding (HASBLED ≥ 3, or need for DAPT) • High thromboembolic risk and time in therapeutic range < 65% • High thromboembolic risk and unwilling to take anticoagulants • Treatment of choice – best therapeutic option – patient choice Camm A.J. 2011

  18. Thank you for your attention

More Related