Anticoagulatie en de oudere patint: Terughoudenheid gerechtvaardigd - PowerPoint PPT Presentation

Anticoagulatie en de oudere patiënt: Terughoudenheid gerechtvaardigd of niet? 16/06/2018 apr. Julie Hias Satellite symposium supported by the Alliance BMS/Pfizer 432BE18PR03459/ 180570 (Date of Preparation: June 2018)

Overview • Introduction • Different OACs • Typical pitfalls to start OACs • Conclusion

Importance of medication review in older patients • Physiological changes • Increase in comorbidities • Increase in number of drugs • Consequences: • Interactions • Adverse drug events • Suboptimal prescribing: – Admission to the hospital – Morbidity – Overuse – Mortality – Inappropriate use – underuse • Functionality • Decrease of medication compliance – Fallrisk – Cognitive decline Gerry R Boss et al. Western Journal of Medicine 1982 Spinewine A et al. Lancet 2007. Hanlon JT et al. J Am Geriatr Soc 2001. Barnet Lancet 2012

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

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

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, 2893–2962

Undertreatment Xian et al. JAMA 2017

Stroke prevention atrial fibrillation (SPAF) European Heart Journal (2016) 37, 2893–2962

NOACs: New/non-VKA oral anticoagulants Dabigatran Rivaroxaban Apixaban Edoxaban (Pradaxa � ) (Xarelto � ) (Eliquis � ) (Lixiana � ) Direct selective reversible Direct selective reversible Direct selective reversible Direct selective reversible Mechanism of Action inhibition of thrombin inhibitor of FXa inhibition of FXa inhibition of FXa Bioavailability 3-7% ~66-100% ~50% ~62% Time to Cmax 1-2 hrs 2.5-4 hrs 3 hrs 1-2 hrs Half-life 12-17 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% CYP 3A4 substrate and P-gp CYP 3A4 substrate and P-gp Potential drug interactions P-gp inhibitor P-gp inhibitor inhibitor 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.

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;383:955-962 .

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;383:955-962 .

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;383:955-962 .

Typical ‘problems’ in elderly patients • Age • Polypharmacy • Renal insufficiency • Fall risk � undertreatment

AGE • Dosisreductie obv leeftijd – Dabigatran: 110mg BID ≥ 80j – Apixaban: 2,5 mg BID ≥ 80j + nog een bijkomende factor • Lichaamsgewicht ≤ 60kg European Heart Journal (2017) • Serumcreatinine ≥ 1,5mg/dl 38, 860–868

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

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 • Dabigatran (Be) >30ml/min • Apixaban, rivaroxaban en edoxaban >15ml/min European Heart Journal (2017) 38, 860–868 European Heart Journal (2018) 39, 1330–1393

Fall risk NNT with Edoxaban 60/30 mg to Avoid an Adverse Event Stratified by Fall Risk Steffel J, et al. JACC. 2016 BE-2016-101

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, 2893–2962 European Heart Journal (2018) 39, 1330–1393 Wehling M. Drugs Aging. 2017

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

Thank you for your attention!