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

16/06/2018

• apr. Julie Hias

Anticoagulatie en de oudere patiënt: Terughoudenheid gerechtvaardigd of niet?

Satellite symposium supported by the Alliance BMS/Pfizer

432BE18PR03459/ 180570 (Date of Preparation: June 2018)

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

Overview

• Physiological changes
• Increase in comorbidities
• Increase in number of drugs
• Consequences:
• Interactions
• Suboptimal prescribing:

– Overuse – Inappropriate use – underuse

• Decrease of medication compliance

Importance of medication review in older patients

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

• Adverse drug events

– Admission to the hospital – Morbidity – Mortality

• Functionality

– Fallrisk – Cognitive decline

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 (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 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% 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.

NOACs – Efficacy in AF trials

• 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.

No adequate and well-controlled head-to-head clinical trials have been conducted comparing the efficacy and safety

• f apixaban versus rivaroxaban, dabigatran, or edoxaban.

Meta-analysis large RCTs - pooled NOACs compared to warfarin

Ruff CT et al. Lancet. 2014;383:955-962.

• 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.

No adequate and well-controlled head-to-head clinical trials have been conducted comparing the efficacy and safety

• f apixaban versus rivaroxaban, dabigatran, or edoxaban.

Meta-analysis large RCTs - pooled NOACs compared to warfarin

NOACs - Safety in AF trials

Ruff CT et al. Lancet. 2014;383:955-962.

NOACs - Secondary endpoints, including GI bleedings

• 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.

.

No adequate and well-controlled head-to-head clinical trials have been conducted comparing the efficacy and safety

• f apixaban versus rivaroxaban, dabigatran, or edoxaban.

Meta-analysis large RCTs - pooled NOACs compared to warfarin

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
• Serumcreatinine ≥1,5mg/dl

European Heart Journal (2017) 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

BE-2016-101

Steffel J, et al. JACC. 2016

Fall risk

NNT with Edoxaban 60/30 mg to Avoid an Adverse Event Stratified by Fall Risk

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!