AF in Asian: which NOAC to choose for particular patient and at what dose? DEJIA HUANG West China Hospital of Sichuan University, Chengdu, China

Transcription

1 AF in Asian: which NOAC to choose for particular patient and at what dose? DEJIA HUANG West China Hospital of Sichuan University, Chengdu, China

2 Case report 64-year-old Chinese man with history of hypertension, COPD and paroxysmal AF; Persistent AF since 3 months ago; No other underlying diseases. BP: 136/82 mmhg. No chest pain; No renal or liver dysfunction. Medications: Perindopril 8mg daily, Verapamil 80mg tid

3 What is the risk of stroke and major bleeding for this Chinese man CHA 2 DS 2 -VASc Score Risk of Stroke Stroke rate (% per year) % 2 2.2% 3 3.2% 4 4.0% 5 6.7% 6 9.8% 7 9.6% 8 6.7% % Risk of Bleeding HAS-BLED Score Bleeding rate (% per year) % % % % 4 8.7% % Am Heart J 2006; 151:713 Eur Heart J 2010; 31:2369

4 What is the risk of stroke? According to a real world cohort of Chinese AF patients in Hong Kong (n=9727), the risk of stroke is 6.64% per year. Siu CW et al. Heart Rhythm 2014; 11:1401

5 What is the risk of stroke? According to Taiwan AF cohort (n=186,570), the risk of stroke is 2.11% per year. Chao TF, et al. Heart Rhythm 2016; 13:46

6 What is the risk of stroke? According to Taiwan BNHI database (n=7920), the risk of stroke is 0.5% per year. Lin LY, et al. Atherosclerosis 2011; 217: 292

7 What is the risk of stroke? According to Swedish National Register data (n=140,420), the risk of stroke is 0.7% per year.

8 What is the really risk of stroke for this Chinese man? 1.3% per year (Euro Heart Survey 2006) 6.64% per year (Hong Kong Cohort 2014) 2.11% per year (Taiwan AF Cohort 2016) 0.50% per year (Taiwan BNHI database 2011) 0.70% per year (Swedish National Register data) Which one do you choose?

9 How do you predict the stroke risk for this patient? The tricky part is that the risk of stroke for this patient with CHA 2 DS 2 -VASc score of 1 may range from 0.5% to 6.64% yearly according to different cohorts. Everyone who take an anticoagulant incurs an increased risk of bleeding. If he was at low risk of stroke, he may get no net clinical benefit from the drug. What is the threshold of stroke risk for net benefit of anticoagulation (Warfarin Vs. NOACs): 1% or 2%?

10 Do you prescribe an anticoagulant for this patient? Warfarin? Risk of stroke: Hong Kong Cohort: 6.64% Taiwan AF Cohort: 2.11% Risk of bleeding: 1.88% (HAS-Bled)? NOACs? If the risk of stroke for this patient is less than 2% per year: Euro Heart Survey 1.3%, Taiwan BNHI data 0.50%, and Swedish National Register data 0.70%.

11 INR 2-3 NOAC Vs. Warfarin

12 Therapeutic window of dabigatran: not so broad

13 NOACs Vs. Warfarin All cause mortality Risk ratio (95%CI) Major bleeding Risk ratio (95%CI) RE-LY (150mg) 0.88 ( ) 0.94 ( ) ROCKET-AF 0.92 ( ) 1.03 ( ) ARISTOTLE 0.89 ( ) 0.71 ( ) ENGAGE-AF (60mg) 0.92 ( ) 0.80 ( ) Combined (n=58,498) 0.90 ( ) P= ( ) P=0.06 Ruff CT, et al. Lancet 2014; 383:955

14 % / Year Rates of Major Bleeding in Asian Patients in RE-LY Trial Hori M et al. 2 nd Asia Pacific Stroke Conference.

15 Which of the NOACs will you prescribe to our patient and at what dose? A) Dabigatran (150mg or 110mg Bid) B) Rivaroxaban (20mg or 15mg Qd) C) Apixaban (5mg or 2.5mg Bid) D) Edoxaban (60mg or 30mg Qd)

16 Safety of NOACs Major bleeding (% per year) Fatal bleeding (% per year) Intracranial bleeding (% per year) Dabigatran Edoxaban Rivaroxaban Apixaban Data from DE-LY, ROCKET-AF, ARISTOTLE and ENGAGE-AF trials

17 Major bleeding in ENGAGE-AF trial 4.0% 3.5% 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% 3.43% P<0.01 P< % 1.61% Warfarin Edoxaban 60mg Edoxaban 30mg Giugliano RP, et al. NEJM 2013; 369:2093

18 Reduced bleeding Reduced mortality: lower dose may be better Edoxaban 60mg Warfarin -59 Edoxaban 30mg Warfarin Prior non-fatal bleeds Bleeds contributed to death Fatal bleeds -88 Giugliano RP, et al. ESC 2014

19 Low Vs. High dose More ischemic events but less bleeding; Preventing excess drug exposure in vulnerable patients.

20 Dose reduction in NOAC trials RE-LY: 2-dose regimens: 110mg Vs. 150mg Bid; ROCKET-AF: 20 15mg Qd for CrCl 30-49ml/min; ARISTOTLE: 5 2.5mg Bid for any tow: age 80 years, body weight 60kg and serum creatinine 1.5mg/dL; ENGAGE-AF: 60-30mg Qd or 30-15mg Qd for CrCl 30-50ml/min; body weight 60kg; use of Quinidine or Verapamil.

21 Heidbuchel H, et al. EHRA guideline Europace. 2013; 15: 625

22 SSE (% pts per year) Dose reduction preserved efficacy: 3.5% 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% All patients 1.80% Warfarin N=7036 ENGAGE-AF trial 1.57% Edo N=14059 No Dose Reduction 1.53% Warfarin N= % Edo N=10490 SSE: Stroke or systematic embolism Dose Reduction 2.68% Warfarin N=1787 P= % Edo and N= % Edo N=1785

23 Major bleeding (% pts per year) Dose reduction with better safety: 6.0% 5.0% 4.0% 3.0% All patients ENGAGE-AF trial No Dose Reduction 3.43% 3.02% 2.75% 2.66% Dose Reduction 4.85% P= % 2.0% 1.50% 1.0% 0.0% Warfarin N=7036 Edo N=14059 Warfarin N=5249 Edo N=10490 Warfarin N=1787 Edo Edo and N=3569 N=1785

24 Our patient: my choice 1) Apixaban 5mg or 2.5mg Bid; 2) Edoxaban 30mg Qd (Verapamil 53%); 3) Rivaroxaban 20mg or 15mg Qd; 4) Dabigatran 110 or 75mg Bid (Verapamil %)

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