Anticoagulatie en de oudere patiënt: Terughoudenheid gerechtvaardigd of niet?

Transcription

1 Anticoagulatie en de oudere patiënt: Terughoudenheid gerechtvaardigd of niet? 16/06/2018 apr. Julie Hias Satellite symposium supported by the Alliance BMS/Pfizer 432BE18PR03459/ (Date of Preparation: June 2018)

2 Overview Introduction Different OACs Typical pitfalls to start OACs Conclusion

3 Importance of medication review in older patients Physiological changes Increase in comorbidities Increase in number of drugs Consequences: Interactions Suboptimal prescribing: Overuse Inappropriate use underuse Decrease of medication compliance Gerry R Boss et al. Western Journal of Medicine 1982 Spinewine A et al. Lancet Hanlon JT et al. J Am Geriatr Soc Barnet Lancet 2012 Adverse drug events Admission to the hospital Morbidity Mortality Functionality Fallrisk Cognitive decline

4 Drugs with a high risk for drug-related (re)admissions Antidiabetic drugs Insulin Oral hypoglycemic agents Antithrombotic drugs Anticoagulants Antiplatelet agents NSAIDs Daniel S. Budnitz N Engl J Med 2011 Daniel S. Budnitz JAMA 2006

5 Common Indications for anticoagulants Venous thromboembolism Treatment Prevention Secondary prevention ACS Mechanical valves Stroke prevention atrial fibrillation

6 Atrial fibrillation ¼ middle-aged adults in Europe and the US will develop AF Greater prevalence Comorbidities: hypertension, heart failure, CAD, obesity, DM, CKD Elderly Higher risk of stroke -> more likely to benefit from OAC Higher bleeding risk -> undertreatment is prevalent European Heart Journal (2016) 37,

7 Xian et al. JAMA 2017 Undertreatment

8 European Heart Journal (2016) 37, Stroke prevention atrial fibrillation (SPAF)

9 NOACs: New/non-VKA oral anticoagulants Dabigatran (Pradaxa ) Rivaroxaban (Xarelto ) Apixaban (Eliquis ) Edoxaban (Lixiana ) Mechanism of Action Direct selective reversible inhibition of thrombin Direct selective reversible inhibitor of FXa Direct selective reversible inhibition of FXa Direct selective reversible inhibition of FXa Bioavailability 3-7% ~66-100% ~50% ~62% Time to Cmax 1-2 hrs hrs 3 hrs 1-2 hrs Half-life hrs 5-9 hrs 8-15 hrs 8-10 hrs Dosing Twice daily Once daily Twice daily Once daily Renal excretion 80% 36% ~27% 35-39% Protein Binding 35% 92-95% 87% 40-59% Potential drug interactions P-gp inhibitor CYP 3A4 substrate and P-gp inhibitor CYP 3A4 substrate and P-gp inhibitor P-gp inhibitor The information in this table is based on the SmPC for Eliquis, Xarelto, Pradaxa and Lixiana. Please refer to the SmPC for further information.

10 NOACs Efficacy in AF trials Meta-analysis large RCTs - pooled NOACs compared to warfarin No adequate and well-controlled head-to-head clinical trials have been conducted comparing the efficacy and safety of apixaban versus rivaroxaban, dabigatran, or edoxaban. Only high-dose data from RE-LY and ENGAGE AF were included in the primary analysis. CI=confidence interval; NOAC=novel oral angcoagulant; RR=relaGve risk; SE=systemic embolism. Ruff CT et al. Lancet. 2014;383:

11 NOACs - Safety in AF trials Meta-analysis large RCTs - pooled NOACs compared to warfarin No adequate and well-controlled head-to-head clinical trials have been conducted comparing the efficacy and safety of apixaban versus rivaroxaban, dabigatran, or edoxaban. Only high-dose data from RE-LY and ENGAGE AF were included in the primary analysis. CI=confidence interval; NOAC=novel oral angcoagulant; RR=relaGve risk; SE=systemic embolism. Ruff CT et al. Lancet. 2014;383:

12 NOACs - Secondary endpoints, including GI bleedings Meta-analysis large RCTs - pooled NOACs compared to warfarin No adequate and well-controlled head-to-head clinical trials have been conducted comparing the efficacy and safety of apixaban versus rivaroxaban, dabigatran, or edoxaban. Only high-dose data from RE-LY and ENGAGE AF were included in the primary analysis. CI=confidence interval; NOAC=novel oral angcoagulant; RR=relaGve risk; SE=systemic embolism.. Ruff CT et al. Lancet. 2014;383:

13 Typical problems in elderly patients Age Polypharmacy Renal insufficiency Fall risk! undertreatment

14 AGE European Heart Journal (2017) 38, Dosisreductie obv leeftijd Dabigatran: 110mg BID 80j Apixaban: 2,5 mg BID 80j + nog een bijkomende factor Lichaamsgewicht 60kg Serumcreatinine 1,5mg/dl

15 Polypharmacy Focks et al. DCRI CommunicaGons October 2015 Efficacy endpoint: no difference Safety endpoint: Bleeding risk increased with number of drugs Major bleeding still < VKA

16 Renal insufficiency Increased risk Bleeding Stroke Exclusion criteria 25(apixaban)-30ml/min Renal excretion: dabigatran > edoxaban > rivaroxaban > apixaban ARISTOTLE trial Major bleeding rate with moderate renal impairment was lower with apixaban than with warfarin Approved European Heart Journal (2017) 38, European Heart Journal (2018) 39, Dabigatran (Be) >30ml/min Apixaban, rivaroxaban en edoxaban >15ml/min

17 Fall risk NNT with Edoxaban 60/30 mg to Avoid an Adverse Event Stratified by Fall Risk Steffel J, et al. JACC BE

18 Guidelines ESCardio: FORTA: Fit for The Aged Apixaban was rated FORTA-A (highly beneficial). Other NOACs and warfarin were assigned to FORTA-B (Beneficial). For other vitamin K antagonists (FORTA-C) regionally used in Europe, the lack of evidence should challenge current practice. European Heart Journal (2016) 37, European Heart Journal (2018) 39, Wehling M. Drugs Aging. 2017

19 Do we need to be afraid? NO! But always be carefull Check compliance Check renal function Evaluate bleeding risk Use recommended dose

20 Thank you for your attention!