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ARISTOTLE TRIAL

ARISTOTLE TRIAL. Dr R Nyabadza GPST1 Ward 32. Structure. AF, stroke and CHA 2 -DS 2 VASC Anticoagulant choices ARISTOTLE trial Cost NICE guidance and the future. AF and Stroke. 1-2% of general population Prevalence to double in next 50 years Increases stroke risk 5-fold

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ARISTOTLE TRIAL

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  1. ARISTOTLE TRIAL Dr R Nyabadza GPST1 Ward 32

  2. Structure • AF, stroke and CHA2-DS2VASC • Anticoagulant choices • ARISTOTLE trial • Cost • NICE guidance and the future

  3. AF and Stroke • 1-2% of general population • Prevalence to double in next 50 years • Increases stroke risk 5-fold • 20% of strokes due to AF • Rhythm control not superior to rate control • Anticoagulation is key • CHA2-DS2VASC Score recommended in new ESC guidelines (2010)

  4. CHA2-DS2VASC Score

  5. Annual stroke risk

  6. New ESC Recommendations

  7. Recent studies RE-LY • Dabigatran 110mg bd: non-inferior to warfarin for stroke and systemic embolism, lower bleeding risk • Dabigatran 150mg bd: lower stroke and systemic embolism, similar haemorrhage risk as warfarin, though  rate of GI bleed

  8. Recent studies contd. AVERROES • Compared apixaban with aspirin in patients intolerant of or unsuitable for VKA • Stopped early due to clear evidence of reduction of stroke and systemic embolism in apixaban 5mg bd group

  9. ARISTOTLEApixaban 5mg bd vs WarfarinSupported by Bristol-Myers Squibb and Pfizer • 18 201 patients: AF or flutter + 1 stroke RF 1034 sites 39 countries • Double blind, double dummy Randomised to apixaban or warfarin Groups well matched

  10. Outcomes • 1° safety outcome: Major bleeding • 1° efficacy outcome: Stroke/systemic embolism • 2° safety outcomes: Clinically relevant non-major bleeding, any bleeding, liver function abnormalities • 2° efficacy outcome: All-cause mortality, MI

  11. Results • Major bleeding: 2.13% vs 3.09% per year (HR 0.69; 95% CI, 0.60 to 0.80; P<0.001) • Intracranial haemorrhage: 0.33% vs 0.8% per year (HR 0.42; 95% CI, 0.30 to 0.58; P<0.001) • Stroke/systemic embolism: 1.27% vs 1.6% per year (HR 0.79; 95% CI, 0.66-0.95; P<0.001) • All-cause mortality: 3.52% vs 3.94% per year (HR 0.89; 95% CI, 0.80 to 0.99; P=0.047) • Cardiovascular mortality: 1.8% vs 2.02% (HR 0.89; 95% CI, 0.76 to 1.04) • Noncardiovascular mortality: 1.14% vs 1.22% (HR 0.93; 95% CI, 0.77 to 1.13)

  12. Results contd. • Reduction in risk of: Systemic embolism by 21% Major bleeding by 31% Death by 11% • For every 1000 patients treated for 1.8 years: 6 strokes prevented (4 haemorrhagic, 2 ischaemic or ?) 15 major bleeding prevented 8 deaths prevented Results consistent geographically and between subgroups

  13. Pros and Cons of ARISTOTLE • Large trial, multi-centred • Adequately powered • Intention-to treat analysis • 380 (2.1%) of patients withdrew consent/lost to follow up • Poor INR control in warfarin group

  14. OACs vs Warfarin • VKAs need monitoring • High inter- and intra-individual variation in INRs • Drug and food interactions • In clinical trials target INR achieved 60-65% of time • In ‘real-life’ often <50% • Below-therapeutic INR for <60% of time may completely offset benefit of VKA • No monitoring needed with new OACs • No reversal agents • Bd dosing

  15. Cost • Apixaban: £102.90 for 30 days • Warfarin: £35.40 for 30 days • NICE currently assessing • Guideline due April 2013

  16. References • Apixaban versus warfarin in patients with atrial fibrillation.Granger CB et al.N Engl J Med. 2011 Sep 15;365(11):981-92 • Stroke and systemic embolism (prevention, non-valvular atrial fibrillation) - apixaban [ID500]. www.nice.org.uk • The RE-LY study: Randomized Evaluation of Long-term anticoagulant therapY: dabigatran vs. warfarin.Camm AJ. Eur Heart J. 2009 Nov;30(21):2554-5. • Apixaban in patients with atrial fibrillation. Connolly SJ et al. N Engl J Med. 2011 Mar 3;364(9):806-17.

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