Antithrombotics in the elderly. Robert Gabor Kiss FESC FACC Budapest

Transcription

1 Antithrombotics in the elderly Robert Gabor Kiss FESC FACC Budapest

2 The patient in the elderly

3 You are sitting in Your office prescribing drugs and observing outcome

4 The black box from prescription to outcome

5 Facing a Virchow triad in the elderly

6 The body Drugs Aging (2016) 33:

7 Cells in vasculature Drugs Aging (2016) 33:

8 The blood

9 Invasive medicine

10

11 Development of Oral Anti-Thrombotic Therapy Post-ACS Reduction in Ischemic Events Increases in Bleeding No Tx ASA Clopidogrel Prasugrel Ticagrelor Vorapaxar Anticoagulant

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13 The drugs in the elderly

14 Dose reductions vary in the elderly Prasugrel (10 to 5 mg) Apixaban (2x5 to 2x2,5 mg) Enoxaparine (1 mg/kg to 0,75 mg/kg) Lot of others are more active in the elderly Less evidence from randomized studies European Heart Journal, 2015; 36:

15 Drugs Aging (2016) 33:

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17 Drugs Aging (2016) 33:

18 Antiplatelets in the elderly

19 Halvorsen S, Andreotti F, ten Berg JM, et al. Aspirin Therapy in Primary Cardiovascular Disease Prevention: A Position Paper of the European Society of Cardiology Working Group on Thrombosis. J Am Coll Cardiol.2014;64(3):

20 Aspirin for primary prevention in Japan JAMA. 2014;312(23):

21 5-year risk (%) 5-year risk (%) 60 Female, entry age years Female, entry age years 50 Vascular death Non-fatal MI/stroke Non-fatal GI or other extracranial bleed 47.7% % % 21% A C A C 10 0 A C A C A C A C 3.9% 4.5% 0.3% 0.2% 0.9% 1.1% 0.9% 0.5% 60 Male, entry age years Male, entry age years 55.8% % % 36.7% A C 20 A C 10 0 A C 8.0% 9.2% A C A C A C 3.4% 3.9% 0.5% 0.3% 1.2% 0.7% Primary Secondary Primary Secondary Aspirin vs none

22 Control Aspirin History None UGI pain Uncomplicated Ulcer Complicated Ulcer 45 Rate of UGIC per 1, < Age person-yrs < Age Aspirin versus none

23 Major bleeding increased with age (>75 years: hazard ratio, 3.10), especially for fatal bleeding (hazard ratio, 5.53) NNT for routine proton pump inhibitor (PPI) use decreased from 338 for individuals younger than 65 years to 25 for individuals aged 85 years and older.

24 Figure 2 The Lancet DOI: ( /S (17) ) Copyright 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

25 Figure 3 The Lancet DOI: ( /S (17) ) Copyright 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

26 OAC in the elderly

27 AF prevalence (%) 80% of all a. fib patients are more than 65 y.o Median age: % % % 40 év felett 65 év felett 75 év felett age Feinberg et al. Arch Intern Med 1995;155:469-73

28 2 y incidence (1000 patients) % Elderly a. fib. patients A. fib. is more frequent in the elderly Aging is a risk for stroke 1,2 55+ : stroke risk doubles by every 10 lifeyears 3 Warfarin can reduce stroke risk by 60% 4 Warfarin induced bleeding is higher in the elderly 5 Stroke 1 Maior bleeding No AF AF age 80 y age<80 y age Days on warfarin 1. Wolf PA et al, Arch Intern Med 1987;147: ; 2. Marinigh R et al, J Am Coll Cardiol 2010;56: ; 3. Sacco RL et al, Stroke 1997;28: ; 4. Hart RG et al, Ann Intern Med 2007;146: ; 5. Hylek EM et al, Circulation 2007;115:

29 29 Kato et al. J Am Heart Assoc 2016;5:e003432

30 Incidence, %/y US real world data. Increased bleeding even on NOAC patients on rivaroxaban; all major bleeds: 2,85%/y < AGE Tamayo S et al, J Am Geriatr Soc 2015;63:s221: abstract C175

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32 OAC versus nothing in the real world setting Presented at ESC 2015;

33 All NOACS: Stroke or SEE Risk Ratio (95% CI) RE-LY [150 mg] 0.66 ( ) ROCKET AF 0.88 ( ) ARISTOTLE 0.80 ( ) ENGAGE AF-TIMI 48 [60 mg] 0.88 ( ) Combined [Random Effects Model] 0.81 ( ) p=< N=58, Favors NOAC 1 Favors Warfarin 2 Heterogeneity p=0.13 Ruff CT, et al. Lancet 2013

34 All NOACS: Major Bleeding RE-LY [150 mg] Risk Ratio (95% CI) 0.94 ( ) ROCKET AF 1.03 ( ) ARISTOTLE 0.71 ( ) ENGAGE AF-TIMI 48 [60 mg] 0.80 ( ) Combined 0.86 ( ) [Random Effects Model] N=58,498 Heterogeneity p=0.001 p= Favors NOAC 1 Favors Warfarin 2 Ruff CT, et al. Lancet 2013

35 Main parameters in different NOAC clinical studies All patients (rivaroxaban) (apixaban) (edoxaban) (dabigatran) ROCKET AF 1 (n=14.264) ARISTOTLE 2 (n=18.201) ENGAGE AF 3 (n=21.105) RE-LY 4,5 (n=18.113) CHADS 2 score 3,5 2,1 2,8 2,1 C CHF, % H Hipertension, % A Age 75 y, % D Diabetes mellitus, % S 2 stroke or TIA, % Patel MR et al, N Engl J Med 2011;365: ; 2. Granger CB et al, N Engl J Med 2011;365: ; 3. Giugliano RP et al, N Engl J Med 2013;369: ; 4. Connolly SJ et al, N Engl J Med 2009;361: ; 5. Eikelboom JW et al, Circulation 2011;123:

36 Safety and efficacy of NOACS compared to warfarin among patients older, than 75 y 1-4 Apixaban 1 n=5 655 Dabigatran 110 mg 1 n=7 258 Dabigatran 150 mg 1 Rivaroxaban 1 n=8 007 Stroke or SE All patients Major bleeding All patients Apixaban better warfarin better 110mg dabigatran better warfarin better 150mg dabigatran better warfarin better rivaroxaban better warfarin better Not a direct comparison! 1. Capranzano et al. Expert Rev Cardiovasc Ther 2013;11:959-73; 2. Granger et al. N Engl J Med 2011;365:981-92; 3. Connolly et al. N Engl J Med 2009;361: ; 4. Patel et al. N Engl J Med 2011;365:883-91

37 Net benefit

38 Event prevented (%/y) Net benefit in the elderly. Rocket AF 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0-0,2-0,4 0, # 0,3 0,48 0,41-0,17 75 y <75 y All-cause All cause mortality mortality Non-haemorrhagic hemorrhagic stroke stroke Life Life threatening bleed bleeding # p (interaction) = 0,034 non hemorrhagic stroke Halperin JL et al, Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with NVAF (ROCKET-AF), Circulation 2014;130:

39 Kato et al. J Am Heart Assoc 2016;5:e

40 Events/10000 patient-years Primary Net Clinical Outcome (Stroke, SEE, Death, Major Bleed) < * < Event rates (%/year) Age (yr) < Warfarin Edoxaban 60/30 mg LT, life threatening; SEE, systemic embolic events *P<0.05 for comparison vs warfarin Kato et al. J Am Heart Assoc 2016;5:e003432

41 Net clinical benefit (all age) Renda G. Am J Med. 2015;128:

42 Being too defensive.

43 % Reduced dose of apixaban in studies and in the real world Klinikai Randomized vizsgálat studies Real world 5 0 Apixaban reduced dose apixaban csökkentett dózis Weitz JI, Eikelboom JW. Appropriate Apixaban Dosing. JAMA Cardiol. 2016; 1(6): doi: /jamacardio

44 Reduced NOAC dosing in real world UK Germany France Fay et al; ESC Poster P2597; Aug 2016

45 Danish Registry. Nielsen PB et al, BMJ 2017;356;j510

46 NOACs dosing

47 Parenteral antithrombotics in the elderly

48 LMWH (enoxaparine) in the elderly March Br J Cardiol 2008;15:87-94

49 GPI in the elderly

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51 Conclusions Bleeding and thrombosis risk high and prothrombotic mechanisms are more active in the elderly Elderly patients should be treated with antithrombotic drugs (MI, a fib etc) as indicated Don t be too defensive Co-morbidities, concomittant therapies should be taken into careful consideration at drug and dose selection Patients and his/her labs should be followed frequently and rigorously