KCS Congress: Impact through collaboration

Transcription

1 Stroke Prevention in Atrial Fibrillation (SPAF) in Kenya Elijah N. Ogola FACC University of Nairobi Kenya Cardiac Society Annual Scientific Congress Mombasa 28 th June 1 st July 2017 KCS Congress: Impact through collaboration

2 Disclosures Transport and accommodation costs by Bayer

3 Outline Preamble Burden of stroke in A.fib OAC therapy NOACs (DOACs) Certain special situations

4

5 KNH Nduiga (2008) Mean age 48yrs, non valvular older Valvular -47% Hypertension 28.9%, Non valvular 53.5% Antithrombotic treatment: o Warfarin 60% o Aspirin 20% o Untreated 20% INR: o Target Ideal 60%; Low 24% ; High 16% o Frequency About every 3 months

6

7 AF has serious consequences Independent risk factor for stroke Approximately fivefold increased risk 1 1 in 6 strokes occur in patients with AF 2 AF-related strokes are typically more severe than strokes due to other aetiologies 3,4 Stroke risk is unaltered even in patients with asymptomatic or intermittent AF 5 Independent risk factor for mortality Approximately twofold increased risk 6 Independent risk factor for heart failure Heart failure further aggravates AF, worsening overall prognosis 7 1. Wolf PA et al. Stroke 1991;22: ; 2. Fuster V et al. Circulation 2006;114:e257 e354; 3. Lin HJ et al. Stroke 1996;27: ; 4. Jørgensen HS et al. Stroke 1996;10: ; 5. Page RL et al. Circulation 2003;107: ; 6. Benjamin EJ et al. Circulation 1998;98: ; 7.Wang T et al. Circulation 2003;107:

8 Stroke risk factors in Kenya Risk factor Overall Ischemic N (%) Hemorrhagic N (%) P-value Hypertension 531(76.8) 266(70.4) 261(81.6) <0.001 DM 101(14.9) 64(16.9) 37(12.2) Hypercholesterolemia 19(2.7) 15(4) 4(1.3) Smoking 111(16.1) 56(14.8) 55(18.1) 0.24 Atrial fibrillation 42(6.1) 41(10.8) 1(0.3) <0.001 Oral contraceptives 27(3.9) 14(3.7) 13(4.3) 0.71 HIV 55(8) 47(12.4) 8(2.6) <0.001

9

10 Antithrombotic Therapy to Prevent Stroke in Patients who Have Nonvalvular AF (Meta-Analysis) Adjusted-dose warfarin compared with placebo or control Antiplatelet agents compared with placebo or control Adjusted-dose warfarin compared with antiplatelet agents Adapted with permission from Hart et al.

11 CHA 2 DS 2 -VASc score and stroke risk in patients with AF Item Previous stroke TIA or systemic embolism Points Age 75 years 2 Congestive heart failure* Hypertension 1 Diabetes mellitus 1 Age years 1 Female gender 1 Vascular disease Add points together CHA 2 DS 2 - VASc 1-year stroke rate % % % % % % % % % % *Or moderate-to-severe left ventricular systolic dysfunction (left ventricular ejection fraction 40%) Olesen JB et al. BMJ 2011;342:d124; Camm AJ et al. Eur Heart J 2010;31:

12 The limitations of VKA therapy Significant inter- and intra-patient variability in dose response, 1 due to: Co-morbid conditions Genetic polymorphisms Numerous interactions with food and concomitant drugs Unpredictable pharmacology Narrow therapeutic window 1 Regular coagulation monitoring and dose adjustments required Failure to stay within the therapeutic range increases the risk of stroke or adverse bleeding events 2 Underuse 2 4 Fear of haemorrhage; intracranial haemorrhage is the most devastating bleeding event 5 Particularly in elderly patients because of high perceived risk of bleeding versus possible benefits 5 1. Ansell J et al. Chest 2008;133:160S 198S; 2. Nieuwlaat R et al. Am Heart J 2007;153: ; 3. Ogilvie IM et al. Am J Med 2010;123: ; 4. Nieuwlaat R et al. Eur Heart J 2005;26: ; 5. Waldo A et al. J Am Coll Cardiol 2005;46:

13 VKAs Have a Narrow Therapeutic Window Risk of ischaemic events Risk of bleeding events Target INR 2 3 INR < 2 INR > 3 Ferreiro JL et al. Thromb Haemost. 2010;103(6):

14 The evolution of anticoagulant drugs 1930s 1940s VKAs 1980s LMWHs 1990s Direct thrombin inhibitors 2002 Indirect Factor Xa inhibitor 2004 Oral direct thrombin inhibitors 2008 Oral direct Factor Xa inhibitors Heparin II, VII, IX, X (Protein C, S) AT + Xa + IIa (1:1 ratio) AT + Xa + IIa (Xa > IIa) IIa AT + Xa IIa Xa Perzborn E et al. Nat Rev Drug Discov 2011;10:61-75

15 Coagulation Cascade Intrinsic Pathway (Contact Activation) XII XI Extrinsic Pathway (Tissue Factor) IX Tissue Factor VIII VII VKAs X Factor Xa Inhibitors (-AT) Apixaban and Rivaroxaban V II Direct Thrombin Inhibitors Dabigatran Fibrinogen Fibrin Clot Adapted with permission from Nutescu et al.

16 Properties of NOACs Property Dabigatran 1,2 Rivaroxaban 1,3 Apixaban 1,4 Edoxaban 1,5,6 Target Thrombin Factor Xa Factor Xa Factor Xa Half-life (hours) T max (hours) Protein binding 34 35% 92 95% 87% 40 59% Dialysis possible for removal? Renal clearance 85% Yes No No No 66%; half is inactive drug 27% 35% Hepatic clearance No Yes Yes Minimal Involvement of CYP No Yes (CYP3A4) Yes (CYP3A4) Yes (CYP3A4) CYP = cytochrome P; NOAC = novel oral anticoagulant; T max = time to maximum plasma concentration; 1. Eikelboom JW, Weitz JI. Circulation 2010;121: ; 2. Pradaxa : EU SPC, 2014; 3. Xarelto : EU SPC, 2014; 4. Eliquis : EU SPC, 2014; 5. Mani H et al. Drug Des Devel Ther 2014;8:789 98; 6. Gras J. Drugs Today (Barc) 2011;47:

17

18

19

20

21

22

23

24

25 Renal Impairment

26

27

28 SHUKRAN